97
Views
0
CrossRef citations to date
0
Altmetric
Review

Doxorubicin conjugates: a practical approach for its cardiotoxicity alleviation

, , , , , , , , , , , & show all
Pages 399-422 | Received 04 Dec 2023, Accepted 29 Feb 2024, Published online: 21 Apr 2024

References

  • Carvalho C, Santos RX, Cardoso S, et al. Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009;16(25):3267–3285.
  • Minotti G, Menna P, Salvatorelli E, et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004 Jun;56(2):185–229.
  • Vigevani A, Williamson MJ. Doxorubicin. In: Florey K, editor. Analytical profiles of drug substances. Vol. 9. New York: Academic Press; 1981. p. 245–274.
  • Weiss RB. The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670–686.
  • Pugazhendhi A, Edison T, Velmurugan BK, et al. Toxicity of doxorubicin (Dox) to different experimental organ systems. Life Sci. 2018 May 1;200:26–30. doi: 10.1016/j.lfs.2018.03.023.
  • Chatterjee K, Zhang J, Honbo N, et al. Doxorubicin cardiomyopathy. Cardiol. 2010;115(2):155–162. doi: 10.1159/000265166
  • Swift LP, Rephaeli A, Nudelman A, et al. Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res. 2006 May 1;66(9):4863–4871. doi: 10.1158/0008-5472.CAN-05-3410
  • Ondrias K, Borgatta L, Kim DH, et al. Biphasic effects of doxorubicin on the calcium release channel from sarcoplasmic reticulum of cardiac muscle. Circ Res. 1990 Nov;67(5):1167–1174.
  • Olusanya TOB, Haj Ahmad RR, Ibegbu DM, et al. Liposomal drug delivery systems and anticancer drugs. Molecules. 2018;23(4):907. doi: 10.3390/molecules23040907
  • Ibrahim M, Abuwatfa WH, Awad NS, et al. Encapsulation, release, and cytotoxicity of doxorubicin loaded in liposomes, micelles, and metal-organic frameworks: a review. Pharmaceutics. 2022;14(2):254. doi: 10.3390/pharmaceutics14020254
  • Nsairat H, Khater D, Sayed U, et al. Liposomes: structure, composition, types, and clinical applications. Heliyon. 2022 May;8(5):e09394.
  • Calzoni E, Cesaretti A, Polchi A, et al. Biocompatible polymer nanoparticles for drug delivery applications in cancer and neurodegenerative disorder therapies. J Funct Biomater. 2019;10(1):4. doi: 10.3390/jfb10010004
  • Ai S, Jia T, Ai W, et al. Targeted delivery of doxorubicin through conjugation with EGF receptor-binding peptide overcomes drug resistance in human colon cancer cells. Br J Pharmacol. 2013;168(7):1719–1735.
  • Singh Y, Palombo M, Sinko PJ. Recent trends in targeted anticancer prodrug and conjugate design. Curr Med Chem. 2008;15(18):1802–1826. doi: 10.2174/092986708785132997
  • Kiyomiya K, Matsuo S, Kurebe M. Mechanism of specific nuclear transport of adriamycin: the mode of nuclear translocation of adriamycin-proteasome complex. Cancer Res. 2001 Mar 15;61(6):2467–2471.
  • Garner AP, Paine MJ, Rodriguez-Crespo I, et al. Nitric oxide synthases catalyze the activation of redox cycling and bioreductive anticancer agents. Cancer Res. 1999 Apr 15;59(8):1929–1934.
  • Vásquez-Vivar J, Martasek P, Hogg N, et al. Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293–11297. doi: 10.1021/bi971475e
  • Mordente A, Meucci E, Martorana GE, et al. Human heart cytosolic reductases and anthracycline cardiotoxicity. IUBMB Life. 2001 Jul 01;52(1):83–88. doi: 10.1080/15216540252774829
  • Sinha BK. Free radicals in anticancer drug pharmacology. Chem Biol Interact. 1989;69(4):293–317. doi: 10.1016/0009-2797(89)90117-8
  • Pawłowska J, Tarasiuk J, Wolf CR, et al. Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245–252.
  • Begleiter A, Leith MK. Activity of quinone alkylating agents in quinone-resistant cells. Cancer Res. 1990 May 15;50(10):2872–2876.
  • Wang Y, Branicky R, Noë A, et al. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Bio. 2018;217(6):1915–1928. doi: 10.1083/jcb.201708007
  • Lü J-M, Lin PH, Yao Q, et al. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med. 2010;14(4):840–860. doi: 10.1111/j.1582-4934.2009.00897.x
  • Abe C, Miyazawa T, Miyazawa T. Current use of Fenton reaction in drugs and food. Molecules. 2022 Aug 25;27(17):5451.
  • Xu X, Persson HL, Richardson DR. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol. 2005 Aug;68(2):261–271. doi: 10.1124/mol.105.013383
  • Barlési F, Tummino C, Tasei AM, et al. Unsuccessful rechallenge with pemetrexed after a previous radiation recall dermatitis. Lung cancer. 2006 Dec;54(3):423–425.
  • Burris HA 3rd, Hurtig J. Radiation recall with anticancer agents. Oncology. 2010;15(11):1227–1237. doi: 10.1634/theoncologist.2009-0090
  • Di Stefano G, Fiume L, Domenicali M, et al. Doxorubicin coupled to lactosaminated albumin: effects on rats with liver fibrosis and cirrhosis. Dig Liver Dis. 2006 Jun;38(6):404–408.
  • Xiao S, Zhang J, Liu M, et al. Doxorubicin has dose-dependent toxicity on mouse ovarian follicle development, hormone secretion, and oocyte maturation. Toxicol Sci. 2017 Jun 1;157(2):320–329. doi: 10.1093/toxsci/kfx047
  • Bielak-Zmijewska A, Wnuk M, Przybylska D, et al. A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta. Biogerontology. 2014 Feb;15(1):47–64.
  • Zwi L, Caspi O, Arbel G, et al. Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation. 2009 Oct 13;120(15):1513–1523. doi: 10.1161/CIRCULATIONAHA.109.868885
  • Doyle MJ, Lohr JL, Chapman CS, et al. Human induced pluripotent stem cell-derived cardiomyocytes as a model for heart development and congenital heart disease. Stem Cell Rev And Rep. 2015;11(5):710–727. doi: 10.1007/s12015-015-9596-6
  • Song S, Chu L, Liang H, et al. Protective effects of dioscin against doxorubicin-induced hepatotoxicity via regulation of Sirt1/FOXO1/NF-κb signal. Front Pharmacol. 2019;10:1030–1030. doi: 10.3389/fphar.2019.01030
  • Dubey I, Khan S, Kushwaha S. Developmental and reproductive toxic effects of exposure to microplastics: a review of associated signaling pathways [Review]. 2022 Aug 31;4: 4. doi: 10.3389/ftox.2022.901798
  • Qin XJ, He W, Hai CX, et al. Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy. J Appl Toxicol. 2008 Apr;28(3):271–282.
  • Vendramini V, Sasso-Cerri E, Miraglia SM. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status. Reprod Biol Endocrinol. 2010 Jan 10;8(1):3.
  • Aryal B, Jeong J, Rao VA. Doxorubicin-induced carbonylation and degradation of cardiac myosin binding protein C promote cardiotoxicity. Proc Nat Acad Sci. 2014 Feb 04;111(5):2011–2016.
  • Zhang QL, Yang JJ, Zhang HS. Carvedilol (CAR) combined with carnosic acid (CAA) attenuates doxorubicin-induced cardiotoxicity by suppressing excessive oxidative stress, inflammation, apoptosis and autophagy. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2019 Jan;109:71–83. doi: 10.1016/j.biopha.2018.07.037
  • Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013 Feb;65(2):157–170. doi: 10.1111/j.2042-7158.2012.01567.x
  • van der Zanden SY, Qiao X, Neefjes J. New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J. 2021 Nov;288(21):6095–6111. doi: 10.1111/febs.15583
  • Volkova M, Russell R. 3rd. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011 Nov;7(4):214–220. doi: 10.2174/157340311799960645
  • McGowan JV, Chung R, Maulik A, et al. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther. 2017 Feb;31(1):63–75.
  • Rawat PS, Jaiswal A, Khurana A, et al. Doxorubicin-induced cardiotoxicity: an update on the molecular mechanism and novel therapeutic strategies for effective management. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2021 Jul;139:111708. doi: 10.1016/j.biopha.2021.111708
  • Florescu M, Cinteza M, Vinereanu D. Chemotherapy-induced cardiotoxicity. Maedica. 2013 Mar;8(1):59–67.
  • Gabani M, Castañeda D, Nguyen QM, et al. Association of cardiotoxicity with doxorubicin and trastuzumab: a double-edged sword in chemotherapy. Cureus. 2021 Sep;13(9):e18194.
  • Booth LK, Redgrave RE, Folaranmi O, et al. Anthracycline-induced cardiotoxicity and senescence. Frontiers In Aging. 2022;3:1058435. doi: 10.3389/fragi.2022.1058435
  • Anakwue R. Cytotoxic-induced heart failure among breast cancer patients in Nigeria: a call to prevent today’s cancer patients from being tomorrow’s cardiac patients. Ann Afr Med. 2020 Jan;19(1):1–7. doi: 10.4103/aam.aam_24_19
  • Zaorsky NG, Churilla TM, Egleston BL, et al. Causes of death among cancer patients. Ann Oncol. 2017 Feb 1;28(2):400–407. doi: 10.1093/annonc/mdw604
  • Patnaik JL, Byers T, DiGuiseppi C, et al. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 2011 Jun 20;13(3):R64. doi: 10.1186/bcr2901
  • Agha A, Wang X, Wang M, et al. Long-term risk of death from heart disease among breast cancer patients. Front Cardiovasc Med. 2022;9:784409. doi: 10.3389/fcvm.2022.784409
  • Pinder MC, Duan Z, Goodwin JS, et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007 Sep 1;25(25):3808–3815. doi: 10.1200/JCO.2006.10.4976
  • Abdul Sattar S, Ali Faisal S, Shazia Samad M, et al. Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan. BMJ Open. 2013;3(11):e003663.
  • Kim YA, Cho H, Lee N, et al. Doxorubicin-induced heart failure in cancer patients: a cohort study based on the Korean National Health Insurance Database. Cancer Med. 2018 Dec;7(12):6084–6092.
  • Berthiaume JM, Wallace KB. Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol Toxicol. 2007 Jan;23(1):15–25. doi: 10.1007/s10565-006-0140-y
  • Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. The effects of doxorubicin on cardiac calcium homeostasis and contractile function. J Cardiol. 2022 Aug;80(2):125–132. doi: 10.1016/j.jjcc.2022.01.001
  • Gammella E, Maccarinelli F, Buratti P, et al. The role of iron in anthracycline cardiotoxicity. Front Pharmacol. 2014;5:25. doi: 10.3389/fphar.2014.00025
  • He H, Wang L, Qiao Y, et al. Doxorubicin induces endotheliotoxicity and mitochondrial dysfunction via ROS/eNOS/NO pathway. Front Pharmacol. 2019;10:1531. doi: 10.3389/fphar.2019.01531
  • Davies KJ, Doroshow JH. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem. 1986 Mar 5;261(7):3060–3067.
  • Simůnek T, Stérba M, Popelová O, et al. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep. 2009 Jan;61(1):154–171.
  • Wiseman LR, Spencer CD. A review of its use as a cardioprotective agent in patients receiving anthracycline-based chemotherapy. Drugs. 1998 Sep;56(3):385–403. doi: 10.2165/00003495-199856030-00009
  • Sritharan S, Sivalingam N. A comprehensive review on time-tested anticancer drug doxorubicin. Life Sci. 2021 Aug 1;278:119527. doi: 10.1016/j.lfs.2021.119527
  • Renu K, GA V, BT P, et al. Molecular mechanism of doxorubicin-induced cardiomyopathy - an update. Eur J Pharmacol. 2018 Jan 5;818:241–253.
  • Holmberg SR, Williams AJ. Patterns of interaction between anthraquinone drugs and the calcium-release channel from cardiac sarcoplasmic reticulum. Circ Res. 1990 Aug;67(2):272–283. doi: 10.1161/01.RES.67.2.272
  • Arai M, Yoguchi A, Takizawa T, et al. Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription. Circ Res. 2000 Jan 7-21;86(1):8–14. doi: 10.1161/01.RES.86.1.8
  • Olson RD, Mushlin PS, Brenner DE, et al. Doxorubicin cardiotoxicity may be caused by its metabolite, doxorubicinol. Proc Natl Acad Sci U S A. 1988 May;85(10):3585–3589.
  • Piska K, Koczurkiewicz P, Bucki A, et al. Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents. Invest New Drugs. 2017 Jun;35(3):375–385.
  • Jo A, Choi TG, Jo YH, et al. Inhibition of carbonyl reductase 1 safely improves the efficacy of doxorubicin in breast cancer treatment. Antioxid Redox Signaling. 2017 Jan 10;26(2):70–83. doi: 10.1089/ars.2015.6457
  • Wallace KB, Sardão VA, Oliveira PJ. Mitochondrial determinants of doxorubicin-induced cardiomyopathy. Circ Res. 2020 Mar 27;126(7):926–941.
  • Goormaghtigh E, Huart P, Praet M, et al. Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity. Biophys Chem. 1990 Apr;35(2–3):247–257.
  • Houtkooper RH, Vaz FM. Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci. 2008 Aug 01;65(16):2493–2506.
  • Paradies G, Paradies V, De Benedictis V, et al. Functional role of cardiolipin in mitochondrial bioenergetics. Biochim Biophys Acta Bioenerg. 2014 Apr;1837(4):408–417.
  • Aryal B, Rao VA, Mukhopadhyay P. Deficiency in cardiolipin reduces doxorubicin-induced oxidative stress and mitochondrial damage in human B-Lymphocytes. PLOS ONE. 2016;11(7):e0158376. doi: 10.1371/journal.pone.0158376
  • Chakravarti B, Chakravarti DN. Oxidative modification of proteins: age-related changes. Gerontology. 2007;53(3):128–139. doi: 10.1159/000097865
  • Evans MD, Dizdaroglu M, Cooke MS. Oxidative DNA damage and disease: induction, repair and significance. Mutat Res/Rev Mutat Res. 2004 Sep 01;567(1):1–61.
  • Su LJ, Zhang JH, Gomez H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019;2019:5080843. doi: 10.1155/2019/5080843
  • Zhang J, Wang X, Vikash V, et al. ROS and ROS-Mediated Cellular Signaling. Oxid Med Cell Longevity. 2016 Feb 22;2016:4350965.
  • Shih NL, Cheng TH, Loh SH, et al. Reactive oxygen species modulate angiotensin II-induced beta-myosin heavy chain gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in neonatal rat cardiomyocytes. Biochem Biophys Res Commun. 2001 Apr 27;283(1):143–148. doi: 10.1006/bbrc.2001.4744
  • Kietzmann T, Petry A, Shvetsova A, et al. The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol. 2017 Jun;174(12):1533–1554.
  • Hori M, Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res. 2009 Feb 15;81(3):457–464.
  • Feno S, Butera G, Vecellio Reane D, et al. Crosstalk between calcium and ROS in pathophysiological conditions. Oxid Med Cell Longev. 2019;2019:9324018. doi: 10.1155/2019/9324018
  • Zhu H, Sarkar S, Scott L, et al. Doxorubicin redox biology: redox cycling, topoisomerase inhibition, and oxidative stress. Reactive Oxygen Species (Apex, NC). 2016;1(3):189–198.
  • McClendon AK, Osheroff N. DNA topoisomerase II, genotoxicity, and cancer. Mutat Res. 2007 Oct 1;623(1–2):83–97.
  • Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009 May 01;9(5):338–350.
  • Marinello J, Delcuratolo M, Capranico G. Anthracyclines as topoisomerase II poisons: from early studies to new perspectives. Int J Mol Sci. 2018 Nov 6;19(11):3480.
  • Tewey KM, Rowe TC, Yang L, et al. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466–468. doi: 10.1126/science.6093249
  • Arcamone F, Cassinelli G, Fantini G, et al. Adriamycin, 14-hydroxydaunomycin, a new antituinor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 2000 Jan 01;67(6):711–713. doi: 10.1002/(SICI)1097-0290(20000320)67:6<704:AID-BIT8>3.0.CO;2-L
  • Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 2014 Oct;10(4):853–858. doi: 10.4103/0973-1482.139267
  • Enna SJ, Bylund DB. Doxorubicin. xPharm: The Comprehensive Pharmacology Reference. New York, NY, USA: Elsevier; 2011.
  • Young RC, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. N Engl J Med. 1981 Jul 16;305(3):139–153.
  • Tavoloni N, Guarino AM, Berk PD. Photolytic degradation of adriamycin. J Pharm Pharmacol. 1980 Dec;32(12):860–862. doi: 10.1111/j.2042-7158.1980.tb13094.x
  • Williams BA, Tritton TR. Photoinactivation of anthracyclines. Photochem photobiol. 1981 Jul 01;34(1):131–134. doi: 10.1111/j.1751-1097.1981.tb08974.x
  • Tomlinson E, Malspeis L. Concomitant adsorption and stability of some anthracycline antibiotics. J Pharm Sci. 1982 Oct;71(10):1121–1125. doi: 10.1002/jps.2600711011
  • Gardiner WA. Possible incompatibility of doxorubicin hydrochloride with aluminum. Am J Health Syst Pharm. 1981 Sep;38(9):1276.
  • May PM, Williams GK, Williams DR. Speciation studies of adriamycin, quelamycin and their metal complexes. Inorganica Chimica Acta. 1980 Jan 01;46:221–228. doi: 10.1016/S0020-1693(00)84195-X
  • Sturgeon RJ, Flanagan C, Naik DV, et al. In vitro adsorption of doxorubicin hydrochloride on insoluble calcium phosphate. J Pharm Sci. 1977 Sep;66(9):1346–1347.
  • Martin SR. Absorption and circular dichroic spectral studies on the self-association of daunorubicin. Biopolymers. 1980 Mar 01;19(3):713–721. doi: 10.1002/bip.1980.360190318
  • Luedke DW, Kennedy PS, Rietschel RL. Histopathogenesis of skin and subcutaneous injury induced by adriamycin. Plast Reconst Surg. 1979 Apr;63(4):463–465. doi: 10.1097/00006534-197904000-00003
  • Sturgeon RJ, Schulman SG. Electronic absorption spectra and protolytic equilibria of doxorubicin: direct spectrophotometric determination of microconstants. J Pharmaceut sci. 1977 Jul 01;66(7):958–961.
  • Yamada Y. Dimerization of doxorubicin causes its precipitation. ACS Omega. 2020 Dec 29;5(51):33235–33241.
  • Yang X, Zhang X, Liu Z, et al. High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Phys Chem C. 2008 Nov 13;112(45):17554–17558. doi: 10.1021/jp806751k
  • Al-Saidi W, Asher SA, Norman P. Resonance raman spectra of TNT and RDX using vibronic theory, excited-state gradient, and complex polarizability approximations. J Phys Chem A. 2012;116(30):7862. doi: 10.1021/jp303920c
  • Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015 Jun 2;131(22):1981–1988. doi: 10.1161/CIRCULATIONAHA.114.013777
  • Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann internal med. 1979 Nov;91(5):710–717.
  • Zamorano JL, Lancellotti P, Rodriguez Munoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur J Heart Fail. 2017 Jan;19(1):9–42.
  • Chen K, Cai H, Zhang H, et al. Stimuli-responsive polymer-doxorubicin conjugate: Antitumor mechanism and potential as nano-prodrug. Acta Biomater. 2019 Jan 15;84:339–355.
  • Ulbrich K, Subr V. Structural and chemical aspects of HPMA copolymers as drug carriers. Adv Drug Deliv Rev. 2010 Feb 17;62(2):150–166.
  • Long S, Dhillon B Man-machine-environment system engineering. Proceedings of the 16th International Conference on MMESE; Xi’an, China. Vol. 406. 2016.
  • Zhong J, Sun P, Xu N, et al. Canagliflozin inhibits p-gp function and early autophagy and improves the sensitivity to the antitumor effect of doxorubicin. Biochem Pharmacol. 2020 May;175:113856. doi: 10.1016/j.bcp.2020.113856
  • Ashrafizadeh M, Mirzaei S, Gholami MH, et al. Hyaluronic acid-based nanoplatforms for Doxorubicin: A review of stimuli-responsive carriers, co-delivery and resistance suppression. Carbohydr Polym. 2021 Nov 15;272:118491.
  • Chen Y, Chen Q, Zhu Q, et al. Small molecular theranostic assemblies functionalized by doxorubicin–hyaluronic acid–methotrexate prodrug for multiple tumor targeting and imaging-guided combined chemo-photothermal therapy. Mol Pharmaceut. 2019 Jun 03;16(6):2470–2480. doi: 10.1021/acs.molpharmaceut.9b00072
  • Jamshidi Z, Sadat Zavvar T, Ramezani M, et al. Dual-targeted and controlled release delivery of doxorubicin to breast adenocarcinoma: In vitro and in vivo studies. Int J Pharmaceut. 2022 Jul 25;623:121892.
  • Hopewel JW, Duncan R, Wilding D, et al. Preclinical evaluation of the cardiotoxicity of PK2: a novel HPMA copolymer–doxorubicin–galactosamine conjugate antitumour agent. Hum Exp Toxicol. 2001 Sep;20(9):461–470.
  • Herman EH, Ferrans VJ, Jordan W, et al. Reduction of chronic daunorubicin cardiotoxicity by ICRF-187 in rabbits. Res Commun Chem Pathol Pharmacol. 1981 Jan;31(1):85–97.
  • Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov. 2003 May 01;2(5):347–360.
  • Stirland DL, Nichols JW, Miura S, et al. Mind the gap: a survey of how cancer drug carriers are susceptible to the gap between research and practice. J Control Release. 2013 Dec 28;172(3):1045–1064. doi: 10.1016/j.jconrel.2013.09.026
  • Vasey PA, Kaye SB, Morrison R, et al. Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign Phase I/II Committee. Clinical Cancer Research: An Official Journal Of The American Association For Cancer Research. 1999 Jan;5(1):83–94.
  • Seymour LW, Ferry DR, Kerr DJ, et al. Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol. 2009 Jun;34(6):1629–1636.
  • Onishi H, Fukasawa A, Miatmoko A, et al. Preparation of chondroitin sulfate-adipic acid dihydrazide-doxorubicin conjugate and its antitumour characteristics against LLC cells. J Drug Targeting. 2017 Sep;25(8):747–753.
  • Lee SJ, Shim Y-H, Oh J-S, et al. Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer nanoparticles for folate-receptor-mediated drug delivery. Nanoscale Res Lett. 2015;10(1):43–43. doi: 10.1186/s11671-014-0706-1
  • Szabó I, Manea M, Orbán E, et al. Development of an oxime bond containing daunorubicin-gonadotropin-releasing hormone-III conjugate as a potential anticancer drug. Bioconjugate Chem. 2009 Apr 15;20(4):656–665. doi: 10.1021/bc800542u
  • Aroui S, Ram N, Appaix F, et al. Maurocalcine as a non toxic drug carrier overcomes doxorubicin resistance in the cancer cell line MDA-MB 231. Pharm Res. 2009 Apr;26(4):836–845.
  • Kaneko T, Willner D, Monkovíc I, et al. New hydrazone derivatives of adriamycin and their immunoconjugates–a correlation between acid stability and cytotoxicity. Bioconjug Chem. 1991 May;2(3):133–141.
  • Froesch BA, Stahel RA, Zangemeister-Wittke U. Preparation and functional evaluation of new doxorubicin immunoconjugates containing an acid-sensitive linker on small-cell lung cancer cells. Cancer Immunol Immun. 1996 Jan;42(1):55–63. doi: 10.1007/s002620050251
  • Caliceti P, Monfardini C, Sartore L, et al. Preparation and properties of monomethoxy poly(ethylene glycol) doxorubicin conjugates linked by an amino acid or a peptide as spacer. Farmaco (Societa chimica italiana : 1989). 1993 Jul;48(7):919–932.
  • Rodrigues PC, Beyer U, Schumacher P, et al. Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution. Bioorg Med Chem. 1999 Nov;7(11):2517–2524.
  • Gabor F, Wollmann K, Theyer G, et al. In vitro antiproliferative effects of albumin-doxorubicin conjugates against Ewing’s sarcoma and peripheral neuroectodermal tumor cells. Anticancer Res. 1994 Sep;14(5a):1943–1950.
  • Kratz F, Beyer U, Roth T, et al. Transferrin conjugates of doxorubicin: synthesis, characterization, cellular uptake, and in vitro efficacy. J Pharm Sci. 1998 Mar;87(3):338–346.
  • Triton TR, Yee G. The anticancer agent adriamycin can be actively cytotoxic without entering cells. Science. 1982 Jul 16;217(4556):248–250.
  • Mizutani H, Tada-Oikawa S, Hiraku Y, et al. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci. 2005 Feb 11;76(13):1439–1453. doi: 10.1016/j.lfs.2004.05.040
  • Duvvuri M, Konkar S, Funk RS, et al. A chemical strategy to manipulate the intracellular localization of drugs in resistant cancer cells. Biochemistry. 2005 Dec 6;44(48):15743–15749. doi: 10.1021/bi051759w
  • Majumdar S, Siahaan TJ. Peptide-mediated targeted drug delivery. Med Res Rev. 2012 May;32(3):637–658. doi: 10.1002/med.20225
  • Majumdar S, Tejo BA, Badawi AH, et al. Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60. Mol Pharmaceut. 2009 Mar;6(2):396–406.
  • Majumdar S, Kobayashi N, Krise JP, et al. Mechanism of internalization of an ICAM-1-derived peptide by human leukemic cell line HL-60: influence of physicochemical properties on targeted drug delivery. Mol Pharmaceut. 2007 Sep;4(5):749–758.
  • Meyer-Losic F, Quinonero J, Dubois V, et al. Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell). J Med Chem. 2006 Nov 16;49(23):6908–6916. doi: 10.1021/jm0606591
  • Krauss U, Kratz F, Beck-Sickinger AG. Novel daunorubicin-carrier peptide conjugates derived from human calcitonin segments. J Mol Recognit. 2003 Sep;16(5):280–287. doi: 10.1002/jmr.638
  • Ziaei E, Paiva IM, Yao SJ, et al. Peptide-drug conjugate targeting keratin 1 inhibits triple-negative breast cancer in mice. Mol Pharmaceut. 2023 Jul 3;20(7):3570–3577. doi: 10.1021/acs.molpharmaceut.3c00189
  • Liu S, Tian Y, Jiang S, et al. A novel homodimer peptide–drug conjugate improves the efficacy of HER2-positive breast cancer therapy. IJMS. 2023 Feb 27;24(5):4590. doi: 10.3390/ijms24054590
  • Fu C, Yu L, Miao Y, et al. Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope? Acta Pharm Sin B. 2023 Feb;13(2):498–516. doi: 10.1016/j.apsb.2022.07.020
  • Ziaei E, Saghaeidehkordi A, Dill C, et al. Targeting triple negative breast cancer cells with novel cytotoxic peptide-doxorubicin conjugates. Bioconjugate Chem. 2019;30(12):3098–3106.
  • Patil R, Portilla-Arias J, Ding H, et al. Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(β-l-malic acid). Int J Mol Sci. 2012;13(9):11681–11693.
  • Sun CY, Dou S, Du JZ, et al. Doxorubicin conjugate of poly(ethylene glycol)-block-polyphosphoester for cancer therapy. Adv Healthc Mater. 2014 Feb;3(2):261–272.
  • Nagy A, Schally AV, Armatis P, et al. Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7269–7273. doi: 10.1073/pnas.93.14.7269
  • Schally AV, Nagy A. Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors. Eur J Endocrinol. 1999 Jul;141(1):1–14. doi: 10.1530/eje.0.1410001
  • Halmos G, Nagy A, Lamharzi N, et al. Cytotoxic analogs of luteinizing hormone-releasing hormone bind with high affinity to human breast cancers. Cancer Lett. 1999 Mar 1;136(2):129–136. doi: 10.1016/S0304-3835(98)00316-4
  • Nagy A, Armatis P, Schally AV. High yield conversion of doxorubicin to 2-pyrrolinodoxorubicin, an analog 500-1000 times more potent: structure-activity relationship of daunosamine-modified derivatives of doxorubicin. Proc Nat Acad Sci. 1996 Mar 19;93(6):2464–2469.
  • Wang J, Wang TT, Gao PF, et al. Biomolecules-conjugated nanomaterials for targeted cancer therapy [10.1039/C4TB01263A]. J Mat Chem B. 2014;2(48):8452–8465. doi: 10.1039/C4TB01263A
  • Garcia AG, Nedev H, Bijian K, et al. Reduced in vivo lung metastasis of a breast cancer cell line after treatment with Herceptin mAb conjugated to chemotherapeutic drugs. Oncogene. 2013 May 01;32(20):2527–2533. doi: 10.1038/onc.2012.283
  • Hafeez U, Parakh S, Gan HK, et al. Antibody–drug conjugates for cancer therapy. Molecules. 2020 Oct 16;25(20):4764. doi: 10.3390/molecules25204764
  • Saleh MN, Sugarman S, Murray J, et al. Phase I trial of the anti-Lewis Y drug immunoconjugate BR96-doxorubicin in patients with Lewis Y-expressing epithelial tumors. J Clin Oncol. 2000 Jun;18(11):2282–2292.
  • Tolcher AW, Sugarman S, Gelmon KA, et al. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J Clin Oncol. 1999 Feb;17(2):478–484.
  • Ajani JA, Kelsen DP, Haller D, et al. A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma. Cancer J. 2000 Mar;6(2):78–81.
  • Zhang N, Klegerman M, Deng H, et al. Trastuzumab-doxorubicin conjugate provides enhanced anti-cancer potency and reduced cardiotoxicity. J Cancer Therapy. 2013 Jan 01;4(1):308–322. doi: 10.4236/jct.2013.41038
  • You Y, Xu Z, Chen Y. Doxorubicin conjugated with a trastuzumab epitope and an MMP-2 sensitive peptide linker for the treatment of HER2-positive breast cancer. Drug Delivery. 2018;25(1):448–460. doi: 10.1080/10717544.2018.1435746
  • Emami F, Banstola A, Vatanara A, et al. Doxorubicin and anti-PD-L1 antibody conjugated gold nanoparticles for colorectal cancer photochemotherapy. Mol Pharmaceut. 2019 Mar 04;16(3):1184–1199. doi: 10.1021/acs.molpharmaceut.8b01157
  • Hermentin P, Seiler FR. Investigations with monoclonal antibody drug (anthracycline) conjugates. Behring Inst Mitt. 1988 Apr;82:197–215.
  • Hurwitz E, Levy R, Maron R, et al. The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Cancer Res. 1975 May;35(5):1175–1181.
  • Hurwitz E, Maron R, Bernstein A, et al. The effect in vivo of chemotherapeutic drug—antibody conjugates in two murine experimental tumor systems. Int J Cancer. 1978 Jun 15;21(6): 747–755. doi: 10.1002/ijc.2910210612
  • Wagner-Rousset E, Janin-Bussat MC, Colas O, et al. Antibody-drug conjugate model fast characterization by LC-MS following IdeS proteolytic digestion. MAbs. 2014 Jan;6(1):273–285.
  • Esnault C, Schrama D, Houben R, et al. Antibody-drug conjugates as an emerging therapy in oncodermatology. Cancers (Basel). 2022;14(3):778.
  • Gründker C, Günthert AR, Westphalen S, et al. Biology of the gonadotropin-releasing hormone system in gynecological cancers. Eur J Endocrinol. 2002 Jan;146(1):1–14.
  • Limonta P, Montagnani Marelli M, Mai S, et al. GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies. Endocrine Reviews. 2012 Oct;33(5):784–811.
  • Polgár L, Lajkó E, Soós P, et al. Drug targeting to decrease cardiotoxicity - determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells. Beilstein J Org Chem. 2018;14:1583–1594. doi: 10.3762/bjoc.14.136
  • Lohlamoh W, Soontornworajit B, Rotkrua P. Anti-proliferative effect of doxorubicin-loaded AS1411 aptamer on colorectal cancer cell. Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2209–2219.
  • Calderan L, Malatesta M. Imaging techniques in nanomedical research. Eur J Histochem. 2020 Jul 1;64(3). doi: 10.4081/ejh.2020.3151
  • Curley CT, Mead BP, Negron K, et al. Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection. Sci adv. 2020;6(18):eaay1344. doi: 10.1126/sciadv.aay1344
  • Le Floc’h J, Lu HD, Lim TL, et al. Transcranial photoacoustic detection of blood-brain barrier disruption following focused ultrasound-mediated nanoparticle delivery. Mol Imaging Biol. 2020 Apr;22(2):324–334.
  • Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020 Aug;17(8):474–502. doi: 10.1038/s41569-020-0348-1
  • Lang T, Liu Y, Zheng Z, et al. Cocktail strategy based on spatio-temporally controlled nano device improves therapy of breast cancer. Adv Mater. 2019 Feb;31(5):e1806202.
  • Wang Y, Yang P, Zhao X, et al. Multifunctional cargo-free nanomedicine for cancer therapy. Int J Mol Sci. 2018;19(10):2963. doi: 10.3390/ijms19102963
  • Siva D, Abinaya S, Rajesh D, et al. Mollification of doxorubicin (DOX)-mediated cardiotoxicity using conjugated chitosan nanoparticles with supplementation of propionic acid. Nanomaterials (Basel). 2022;12(3):502. doi: 10.3390/nano12030502
  • Odeh F, Nsairat H, Alshaer W, et al. Aptamers chemistry: chemical modifications and conjugation strategies. Molecules. 2020;25(1):3. doi: 10.3390/molecules25010003
  • Dou XQ, Wang H, Zhang J, et al. Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity. Int j nanomed. 2018;13:763–776.
  • Kuruvilla SP, Tiruchinapally G, Crouch AC, et al. Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model. PLOS ONE. 2017;12(8):e0181944. doi: 10.1371/journal.pone.0181944
  • She W, Li N, Luo K, et al. Dendronized heparin−doxorubicin conjugate based nanoparticle as pH-responsive drug delivery system for cancer therapy. Biomaterials. 2013 Mar 01;34(9):2252–2264. doi: 10.1016/j.biomaterials.2012.12.017
  • Mitra S, Gaur U, Ghosh PC, et al. Tumour targeted delivery of encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier. JControlled Release. 2001 Jul 06;74(1):317–323. doi: 10.1016/S0168-3659(01)00342-X
  • Sun C, Lu C-T, Zhao Y-Z. Characterization of the doxorubicin-pluronic F68 conjugate micelles and their effect on doxorubicin resistant human erythroleukemic cancer cells. J Nanomedic Nanotechnol. 2011 Jan 02;2(05). doi: 10.4172/2157-7439.1000114
  • Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Natural Prod. 2003 Jul;66(7):1022–1037. doi: 10.1021/np030096l
  • Ojha S, Al Taee H, Goyal S, et al. Cardioprotective potentials of plant-derived small molecules against doxorubicin associated cardiotoxicity. Oxid Med Cell Longev. 2016;2016:5724973. doi: 10.1155/2016/5724973
  • Yu J, Wang C, Kong Q, et al. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine. 2018 Feb 1;40:125–139.
  • Dong Q, Chen L, Lu Q, et al. Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression. Br J Pharmacol. 2014 Oct;171(19):4440–4454.
  • Kyaw M, Yoshizumi M, Tsuchiya K, et al. Atheroprotective effects of antioxidants through inhibition of mitogen-activated protein kinases. Acta Pharmacol Sin. 2004 Aug;25(8):977–985.
  • Hashish F, Abdel-Wahed M, El-Odemi M, et al. Possible protective effects of quercetin on doxorubicin-induced cardiotoxicity in rats. Menoufia Med J. 2021 Jan 01;34(1):333. doi: 10.4103/mmj.mmj_5_20
  • Moutabian H, Ghahramani-Asl R, Mortezazadeh T, et al. The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: a systematic review. BioFactors. 2022 May 01;48(3): 597–610. doi: 10.1002/biof.1823
  • Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol. 1998 Jun;124(3):425–427. doi: 10.1038/sj.bjp.0701877
  • Benzer F, Kandemir FM, Ozkaraca M, et al. Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. J Biochem Mol Toxicol. 2018 Feb 01;32(2): e22030. doi: 10.1002/jbt.22030
  • Swamy AV, Gulliaya S, Thippeswamy A, et al. Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol. 2012 Jan;44(1):73–77.
  • Hosseinzadeh L, Behravan J, Mosaffa F, et al. Curcumin potentiates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells through generation of reactive oxygen species. Food Chem Toxicol: An Int J Published Br Ind Biol Res Assoc. 2011 May;49(5):1102–1109.
  • Zhou Z-P, Liu L-N, Chen X-L, et al. Factors that effect antioxidant activity of c-phycocyanins from spirulina platensis. J Food Biochemistry. 2005 Jun 01;29(3): 313–322. doi: 10.1111/j.1745-4514.2005.00035.x
  • Lee H, Kim MA, Lee J-S, et al. C-Phycoycanin-doxorubicin nanoparticles for chemo-photodynamic cancer therapy. Macromol Res. 2022 Jul 01;30(7):486–494. doi: 10.1007/s13233-022-0057-1
  • Liu C, Ma X, Zhuang J, et al. Cardiotoxicity of doxorubicin-based cancer treatment: what is the protective cognition that phytochemicals provide us? Pharmacol Res. 2020 Oct 01;160:105062.
  • Pratesi G, Savi G, Pezzoni G, et al. Poly-L-aspartic acid as a carrier for doxorubicin: a comparative in vivo study of free and polymer-bound drug. Br J Cancer. 1985 Dec 01;52(6):841–848. doi: 10.1038/bjc.1985.267
  • Duncan R, Hume IC, Kopečková P, et al. Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. 3. Evaluation of adriamycin conjugates against mouse leukaemia L1210 in vivo. JControlled Release. 1989 Oct 01;10(1):51–63. doi: 10.1016/0168-3659(89)90017-5
  • Yeung TK, Hopewell JW, Simmonds RH, et al. Reduced cardiotoxicity of doxorubicin given in the form ofN-(2-hydroxypropyl) methacrylamide conjugates: an experimental study in the rat. Cancer Chemother Pharmacol. 1991 Mar 01;29(2):105–111. doi: 10.1007/BF00687318
  • Mosure KW, Henderson AJ, Klunk LJ, et al. Disposition of conjugate-bound and free doxorubicin in tumor-bearing mice following administration of a BR96-doxorubicin immunoconjugate (BMS 182248). Cancer Chemother Pharmacol. 1997;40(3):251–258. doi: 10.1007/s002800050655
  • Comereski CR, Peden WM, Davidson TJ, et al. BR96-doxorubicin conjugate (BMS-182248) versus doxorubicin: a comparative toxicity assessment in rats. Toxicol Pathol. 1994 Sep;22(5):473–488.
  • Venkatesan R, Pichaimani A, Hari K, et al. Doxorubicin conjugated gold nanorods: a sustained drug delivery carrier for improved anticancer therapy. J Mat Chem B. 2013 Feb 21;1(7):1010–1018. doi: 10.1039/C2TB00078D
  • Arunkumar P, Raju B, Vasantharaja R, et al. Near infra-red laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods with reduced cardiotoxicity in swiss albino mice. Nanomedicine. 2015 Aug;11(6):1435–1444.
  • Lu D, Liang J, Fan Y, et al. In Vivo Evaluation of a pH-Sensitive Pullulan–Doxorubicin Conjugate. Adv Eng Mater. 2010 Sep 01;12(9): B496–B503. doi: 10.1002/adem.200980085
  • Zoghebi K, Aliabadi HM, Tiwari RK, et al. [(WR)8WKβA]-Doxorubicin Conjugate: A Delivery System to Overcome Multi-Drug Resistance against Doxorubicin. Cells. 2022 Jan 16;11(2):301. doi: 10.3390/cells11020301
  • Huan ML, Zhou SY, Teng ZH, et al. Conjugation with alpha-linolenic acid improves cancer cell uptake and cytotoxicity of doxorubicin. Bioorganic Med Chem Lett. 2009 May 1;19(9):2579–2584. doi: 10.1016/j.bmcl.2009.03.016
  • Huan M, Cui H, Teng Z, et al. In vivo anti-tumor activity of a new doxorubicin conjugate via α-linolenic acid. Biosci Biotechnol Biochem. 2012;76(8):1577–1579. doi: 10.1271/bbb.120256
  • Swarnakar NK, Thanki K, Jain S. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using doxorubicin- and coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous adriamycin. Nanomedicine. 2014 Aug;10(6):1231–1241. doi: 10.1016/j.nano.2014.03.003
  • Zeng Q, Wen H, Wen Q, et al. Cucumber mosaic virus as drug delivery vehicle for doxorubicin. Biomaterials. 2013 Jun;34(19):4632–4642.
  • Kaminskas LM, Kelly BD, McLeod VM, et al. Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker. J Control Release. 2011 Jun 10;152(2):241–248. doi: 10.1016/j.jconrel.2011.02.005
  • Kaminskas LM, McLeod VM, Kelly BD, et al. Doxorubicin-conjugated PEGylated dendrimers show similar tumoricidal activity but lower systemic toxicity when compared to PEGylated liposome and solution formulations in mouse and rat tumor models. Mol Pharmaceut. 2012 Mar 5;9(3):422–432. doi: 10.1021/mp200522d
  • Liu P, Chen N, Yan L, et al. Preparation, characterisation and in vitro and in vivo evaluation of CD44-targeted chondroitin sulphate-conjugated doxorubicin PLGA nanoparticles. Carbohydr Polym. 2019 Jun 01;213:17–26.
  • Wang H, Liu X, Wang Y, et al. Doxorubicin conjugated phospholipid prodrugs as smart nanomedicine platforms for cancer therapy. J Mat Chem B. 2015;3(16):3297–3305. doi: 10.1039/C4TB01984A
  • Saha P, Fortin S, Leblanc V, et al. Design, synthesis, cytocidal activity and estrogen receptor α affinity of doxorubicin conjugates at 16α-position of estrogen for site-specific treatment of estrogen receptor positive breast cancer. Steroids. 2012 Sep;77(11):1113–1122.
  • Du C, Deng D, Shan L, et al. A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery. Biomaterials. 2013 Apr;34(12):3087–3097.
  • Mizuno Y, Hara T, Tachibana S, et al. Doxorubicin-heparin complex: reduction of cardiotoxicity of doxorubicin. J Cancer Res Clin Oncol. 1995;121(8):469–473.
  • Lale SV, Kumar A, Naz F, et al. Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge effect/endo-lysosomal escape. Polym Chem. 2015;6(11):2115–2132. doi: 10.1039/C4PY01698J
  • Feng C, Rui M, Shen H, et al. Tumor-specific delivery of doxorubicin through conjugation of pH-responsive peptide for overcoming drug resistance in cancer. Int J Pharmaceut. 2017 Aug 7;528(1–2):322–333. doi: 10.1016/j.ijpharm.2017.06.022
  • Chegaev K, Rolando B, Cortese D, et al. H2S-donating doxorubicins may overcome cardiotoxicity and multidrug resistance. J Med Chem. 2016 May 26;59(10):4881–4889. doi: 10.1021/acs.jmedchem.6b00184
  • Darwish S, Sadeghiani N, Fong S, et al. Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide. Eur J Med Chem. 2019;161:594–606. doi: 10.1016/j.ejmech.2018.10.042
  • Vasey PA, Kaye SB, Morrison R, et al. Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl) methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents—drug-polymer conjugates. Clin Cancer Res. 1999;5(1):83–94.
  • Matsumura Y, Hamaguchi T, Ura T, et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 2004;91(10):1775–1781. doi: 10.1038/sj.bjc.6602204
  • Julyan PJ, Seymour LW, Ferry DR, et al. Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine. JControlled Release. 1999;57(3):281–290.
  • Seymour LW, Ferry DR, Anderson D, et al. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002;20(6):1668–1676. doi: 10.1200/JCO.2002.20.6.1668
  • Phase I/II study of hLL1-DOX in relapsed NHL and CLL. Available from: https://classic.clinicaltrials.gov/show/NCT01585688

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.