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Review

Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy

, , , & ORCID Icon
Pages 1385-1398 | Received 18 Jun 2021, Accepted 04 Oct 2021, Published online: 01 Nov 2021

References

  • Christidi E, Brunham LR. Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death Dis. 2021 Apr 1;12(4):339.
  • Mohajeri M, Sahebkar A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance: a review. Crit Rev Oncol Hematol. 2018 Feb;122:30–51.
  • Ma W, Chen Q, Xu W, et al. Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer. Nano Res. 2021 Mar 01;14(3):846–857.
  • Kanwal U, Irfan Bukhari N, Ovais M, et al. Advances in nano-delivery systems for doxorubicin: an updated insight. J Drug Target. 2018 Apr;26(4):296–310.
  • Tan C, Tasaka H, Yu KP, et al. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333–353.
  • Arcamone F, Cassinelli G, Fantini G, et al. Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101–1110.
  • Niraula NP, Kim SH, Sohng JK, et al. Biotechnological doxorubicin production: pathway and regulation engineering of strains for enhanced production. Appl Microbiol Biotechnol. 2010 Jul;87(4):1187–1194.
  • Gorini S, De Angelis A, Berrino L, et al. Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxid Med Cell Longev. 2018;2018:7582730.
  • Tuzovic M, Wu PT, Kianmahd S, et al. Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: systematic review and meta-analysis. Echocardiography. 2018 Jul;35(7):922–934.
  • Fiallo MM, Tayeb H, Suarato A, et al. Circular dichroism studies on anthracycline antitumor compounds. Relationship between the molecular structure and the spectroscopic data. J Pharm Sci. 1998 Aug;87(8):967–975.
  • 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.
  • Contino M, Guglielmo S, Riganti C, et al. One molecule two goals: a selective P-glycoprotein modulator increases drug transport across gastro-intestinal barrier and recovers doxorubicin toxicity in multidrug resistant cancer cells. Eur J Med Chem. 2020 Dec 15;208:112843.
  • Prathumsap N, Shinlapawittayatorn K, Chattipakorn SC, et al. Effects of doxorubicin on the heart: from molecular mechanisms to intervention strategies. Eur J Pharmacol. 2020 Jan 5;866:172818.
  • Smith T, Wolff KA, Nguyen L. Molecular biology of drug resistance in Mycobacterium tuberculosis. Curr Top Microbiol Immunol. 2013;374:53–80.
  • Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003 Jun 1;97(11):2869–2879.
  • Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710–717.
  • Sun D, Zhou S, and Gao W. What went wrong with anticancer nanomedicine design and how to make it right. ACS Nano. 2020 Oct 27;14(10):12281–12290. .
  • Amoh Y, Li L, Katsuoka K, et al. Chemotherapy targets the hair-follicle vascular network but not the stem cells. J Invest Dermatol. 2007 Jan;127(1):11–15.
  • Selleri S, Seltmann H, Gariboldi S, et al. Doxorubicin-induced alopecia is associated with sebaceous gland degeneration. J Invest Dermatol. 2006 Apr;126(4):711–720.
  • Osataphan N, Phrommintikul A, and Chattipakorn SC, et al. Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: insights for future interventions. J Cell Mol Med. 2020 Jun;24(12):6534–6557.
  • Nguyen TT, Lim JS, Tang RM, et al. Fitness profiling links topoisomerase II regulation of centromeric integrity to doxorubicin resistance in fission yeast. Sci Rep. 2015 Feb 11;5:8400.
  • Borišev I, Mrđanovic J, Petrovic D, et al. **Nanoformulations of doxorubicin: how far have we come and where do we go from here? Nanotechnology. 2018 Aug 17;29(33):332002. .
  • Buzun K, Bielawska A, and Bielawski K, et al. DNA topoisomerases as molecular targets for anticancer drugs. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1781–1799. .
  • Robles AI, Wang XW, Harris CC. Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death. Oncogene. 1999 Aug 19;18(33):4681–4688.
  • Coldwell K, Cutts SM, Ognibene TJ, et al. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry. Methods Mol Biol. 2010;613:103–118.
  • Pang B, Qiao X, Janssen L, et al. Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun. 2013;4:1908.
  • Hajipour Verdom B, Abdolmaleki P, Behmanesh M. The static magnetic field remotely boosts the efficiency of doxorubicin through modulating ROS behaviors. Sci Rep. 2018 Jan 17;8(1):990.
  • Myers C. The role of iron in doxorubicin-induced cardiomyopathy. Semin Oncol. 1998 Aug;25(4 Suppl 10):10–14.
  • Wang S, Kotamraju S, Konorev E, et al. Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide. Biochem J. 2002 Nov 1;367(Pt 3):729–740.
  • Wang S, Song P, Zou MH. Inhibition of AMP-activated protein kinase α (AMPKα) by doxorubicin accentuates genotoxic stress and cell death in mouse embryonic fibroblasts and cardiomyocytes: role of p53 and SIRT1. J Biol Chem. 2012 Mar 9;287(11):8001–8012.
  • de Luca A, Moroni N, Serafino A, et al. Treatment of doxorubicin-resistant MCF7/Dx cells with nitric oxide causes histone glutathionylation and reversal of drug resistance. Biochem J. 2011 Dec 1;440(2):175–183.
  • Gonçalves M, Mignani S, and Rodrigues J, et al. A glance over doxorubicin based-nanotherapeutics: from proof-of-concept studies to solutions in the market. J Control Release. 2020 Jan 10;317:347–374.
  • Jiang L, Gao Z-M, Ye L, et al. A tumor-targeting nano doxorubicin delivery system built from amphiphilic polyrotaxane-based block copolymers. Polymer. 2013 Aug 23;54(19):5188–5198.
  • Chen F, Chen H, Duan X, et al. Molecularly imprinted polymers synthesized using reduction-cleavable hyperbranched polymers for doxorubicin hydrochloride with enhanced loading properties and controlled release. J Mater Sci. 2016 Oct 01;51(20):9367–9383.
  • Rusetskaya NV, Lukyanova NY, Chekhun VF. Molecular profile and cell cycle in MCF-7 and MCF-7/Dox cells exposed to conventional and liposomal forms of doxorubicin. Exp Oncol. 2009 Sep;31(3):140–143.
  • Ma P, Mumper RJ. Anthracycline nano-delivery systems to overcome multiple drug resistance: a comprehensive review. Nano Today. 2013 Jun 1;8(3):313–331.
  • Yu P, Yu H, Guo C, et al. Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles. Acta Biomater. 2015 Mar;14:115–124.
  • Dai X, Yue Z, Eccleston ME, et al. Fluorescence intensity and lifetime imaging of free and micellar-encapsulated doxorubicin in living cells. Nanomed. 2008 Mar;4(1):49–56.
  • Hovorka O, St’astný M, Etrych T, et al. Differences in the intracellular fate of free and polymer-bound doxorubicin. J Control Release. 2002 Apr 23;80(1–3):101–117.
  • Minko T, Kopecková P, Kopecek J. Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells. J Control Release. 2001 Apr 28;71(3):227–237.
  • Malugin A, Kopecková P, Kopecek J. Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells. J Control Release. 2007 Dec 4;124(1–2):6–10.
  • Yousefpour P, Atyabi F, Vasheghani-Farahani E, et al. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab. Int J Nanomedicine. 2011;6:1977–1990.
  • Min Y, Caster JM, Eblan MJ, et al. Clinical Translation of Nanomedicine. Chem Rev. 2015 Oct 14;115(19):11147–11190.
  • Caster JM, Patel AN, Zhang T, et al. Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017 Jan;9(1).
  • Havel H, Finch G, Strode P, et al. Nanomedicines: from bench to bedside and beyond. AAPS J. 2016 Nov;18(6):1373–1378.
  • Hassan S, Prakash G, Ozturk A, et al. Evolution and clinical translation of drug delivery nanomaterials. Nano Today. 2017 Aug;15:91–106.
  • Lancaster JM Micro-RNA profiles associated with endometrial cancer development and response to cisplatin and doxorubicin chemotherapy. Google Patents. 2012.
  • Salamone SJ, Courtney JB, He S Doxorubicin immunoassay. Google Patents. 2011.
  • Filippini S, Lomovskaya N, Fonstein L, et al. Process for preparing doxorubicin. Google Patents. 2001.
  • Stewart S, Jablonowski H, Goebel FD, et al. Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma. International Pegylated Liposomal Doxorubicin Study Group. J Clin Oncol. 1998 Feb;16(2):683–691.
  • Gordon AN, Tonda M, Sun S, et al. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1–8.
  • Lyon PC, Griffiths LF, Lee J, et al. Clinical trial protocol for TARDOX: a phase I study to investigate the feasibility of targeted release of lyso-thermosensitive liposomal doxorubicin (ThermoDox®) using focused ultrasound in patients with liver tumours. J Ther Ultrasound. 2017;5:28.
  • Celsion. Phase 3 Study of ThermoDox With Radiofrequency Ablation (RFA) i n Treatment of Hepatocellular Carcinoma (HCC). 2014. [cited 2019 July 17] Available from: https://clinicaltrials.gov/ct2/show/NCT00617981
  • Celsion. Study of ThermoDox With Standardized Radiofrequency Ablation (RFA) for Treatment of Hepatocellular Carcinoma (HCC) (OPTIMA). [cited 2019 June 17]. Available from: https://Clinicaltrials.Gov/Ct2/Show/Study/NCT021126562014
  • Gaspani S, Milani B. Access to liposomal generic formulations: beyond AmBisome and Doxil/Caelyx. GaBi J. 2013;2(2):60–62.
  • Rifkin RM, Gregory SA, Mohrbacher A, et al. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial. Cancer. 2006;106(4):848–858.
  • Miller K, Cortes J, Hurvitz SA, et al. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer. 2016;16(1):1–11.
  • MM-302 Misses Endpoint in Phase II Hermione Trial [Internet]. 2016. Available from: https://adcreview.com/news/mm-302-misses-endpoint-phase-ii-hermione-trial/
  • Lopez-Pousa A, Bui Nguyen B, Garcia del Muro X, et al. A phase II study of a new formulation of nonpegylated liposomal doxorubicin (doxorubicin GP-pharm) as first-line treatment in patients with advanced soft-tissue sarcomas (STS) who are age 65 or older: a GEIS trial. J clin oncol. 2011;29(15_suppl):10072.
  • Mamot C, Ritschard R, Wicki A, et al. Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study. Lancet Oncol. 2012;13(12):1234–1241.
  • Kerklaan BM, Jager A, Aftimos P, et al. NT-23 phase 1/2a study of glutathione pegylated liposomal doxorubicin (2B3-101) in breast cancer patients with brain metastases (BCBM) or recurrent high grade gliomas (HGG). Neuro Oncol. 2014;16(suppl_5):v163–v163.
  • 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;34(6):1629–1636.
  • Onxeo to host a Conference Call today to comment on the main findings from ReLive Phase III Study of Livatag® [Internet]. 2017. [cited July 17]. Available from: https://www.onxeo.com/onxeo-host-conference-call-today-comment-main-findings-relive-phase-iii-study-livatag/
  • Valle J, Lawrance J, Brewer J, et al. A phase II, window study of SP1049C as first-line therapy in inoperable metastatic adenocarcinoma of the oesophagus. J clin oncol. 2004;22(14_suppl):4195.
  • 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.
  • Whittle JR, Lickliter JD, Gan HK, et al. First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma. J Clin Neurosci. 2015;22(12):1889–1894.
  • Muggia FM, Hainsworth JD, Jeffers S, et al. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987–993.
  • Symon Z, Peyser A, Tzemach D, et al. Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes. Cancer. 1999 Jul 1;86(1):72–78.
  • Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892–3901.
  • Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet. 2003;42(5):419–436.
  • Barenholz Y. Doxil®–the first FDA-approved nano-drug: lessons learned. J Control Release. 2012 Jun 10;160(2):117–134.
  • Krown SE, Northfelt DW, Osoba D, et al. Use of liposomal anthracyclines in Kaposi’s sarcoma. Semin Oncol. 2004 Dec;31(6 Suppl 13):36–52.
  • O’Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440–449.
  • Poon RT, Borys N. Lyso-thermosensitive liposomal doxorubicin: an adjuvant to increase the cure rate of radiofrequency ablation in liver cancer. Future Oncol. 2011 Aug;7(8):937–945.
  • Chen J, He CQ, Lin AH, et al. Thermosensitive liposomes with higher phase transition temperature for targeted drug delivery to tumor. Int J Pharm. 2014 Nov 20;475(1–2):408–415.
  • Poon RT, Borys N. Lyso-thermosensitive liposomal doxorubicin: a novel approach to enhance efficacy of thermal ablation of liver cancer. Expert Opin Pharmacother. 2009 Feb;10(2):333–343.
  • Batist G, Barton J, Chaikin P, et al. Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy. Expert Opin Pharmacother. 2002 Dec;3(12):1739–1751.
  • Leonard RC, Williams S, Tulpule A, et al. Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet). Breast. 2009 Aug;18(4):218–224.
  • Chan S, Davidson N, Juozaityte E, et al. Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol. 2004 Oct;15(10):1527–1534.
  • Safra T. Cardiac safety of liposomal anthracyclines. Oncologist. 2003;8(Suppl 2):17–24.
  • Gaillard PJ, Appeldoorn CC, Dorland R, et al. Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101). PloS One. 2014;9(1):e82331.
  • Gaillard PJ, Visser CC, Appeldoorn CCM, et al. Enhanced brain drug delivery: safely crossing the blood–brain barrier. Drug Discovery Today. 2012 Jun 01;9(2):e155–e160.
  • Dalesio O. Clinical and pharmacological study with 2B3-101 in patients with breast cancer and leptomeningeal metastases. Clinicaltrials.Gov., editor. [cited July 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT018187132013.
  • Kattan J, Droz JP, Couvreur P, et al. Phase I clinical trial and pharmacokinetic evaluation of doxorubicin carried by polyisohexylcyanoacrylate nanoparticles. Invest New Drugs. 1992 Aug;10(3):191–199.
  • Onxeo. Orphan oncology products: produits orphelins en oncologie. [cited July 17]. Available from: http://www.onxeo.com/en/nos-produits/orphelins-oncologie/#tabs-1-32019
  • Onxeo. Livatag® (Doxorubicin TransdrugTM) follow up demonstrates significant survival increase in advanced hepatocellular carcinoma patients. [cited July 17]. Available from: http://www.onxeo.com/wpcontent/2011
  • Onxeo. Onxeo announces top-line results from relive phase iii study of livatag® in advanced hepatocellular carcinoma. [cited July 17]. Available from: https://www.onxeo.com/onxeo-announces-top-line-results-relive-phase-iii-study-livatag-advanced-hepatocellular-carcinoma/2017.
  • Reynolds JG, Olivier KJ, Hendriks BS, et al. Dosage and administration for preventing cardiotoxicity in treatment with ERBB2-targeted immunoliposomes comprising anthracycline chemotherapeutic agents. Google Patents. 2016.
  • Park JW, Hong K, Kirpotin DB, et al. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin Cancer Res off J Am Assoc Cancer Res. 2002 Apr;8(4):1172–1181.
  • Park JW, Kirpotin DB, Hong K, et al. Tumor targeting using anti-her2 immunoliposomes. J Control Release. 2001 Jul 6;74(1–3):95–113.
  • Schütz CA, Juillerat-Jeanneret L, Mueller H, et al. Therapeutic nanoparticles in clinics and under clinical evaluation. Nanomedicine (Lond). 2013 Mar;8(3):449–467.
  • Seymour LW, Ferry DR, Anderson D, et al. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002 Mar 15;20(6):1668–1676.
  • 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.
  • Sohail M, Guo W, Li Z, et al. Nanocarrier-based drug delivery system for cancer therapeutics: a review of the last decade. Curr Med Chem. 2021:28(19):3735-3772
  • Ofner III CM, Cammarata C, Rhodes B, et al. High molecular weight biodegradable gelatin-doxorubicin conjugate. Google Patents. 2019.
  • Zhao Y, Cai Z, Tang X, et al. Preoperative denosumab may increase the risk of local recurrence of giant-cell tumor of bone treated with curettage: a systematic review and meta-analysis. J Cancer. 2021;12(2):508.
  • Egorov M, Goujon J-Y, Le Bot R, et al. Hydrosoluble hydroxybisphosphonic derivatives of doxorubicin. Google Patents. 2019.
  • Nieciecka D, Celej J, Żuk M, et al. Hybrid system for local drug delivery and magnetic hyperthermia based on SPIONs loaded with doxorubicin and epirubicin. Pharmaceutics. 2021;13(4):480.
  • Qiao X, van der Zanden SY, Wander DP, et al. Uncoupling DNA damage from chromatin damage to detoxify doxorubicin. Proc Nat Acad Sci. 2020;117(26):15182–15192.
  • Liu C, Liu Y Legumain activated doxorubicin derivative as well as preparation method and application thereof. Google Patents. 2018.
  • Borbély J, Csikós Z, Koncz G, et al. Stable nanocomposition comprising doxorubicin, process for the preparation thereof, its use and pharmaceutical compositions containing it. Google Patents. 2015.
  • Floyd RA, Kopke RD, Choi C-H, et al. Nitrones as therapeutics. Free Radic Biol Med. 2008;45(10):1361–1374.
  • Oliveira C, Benfeito S, Fernandes C, et al. NO and HNO donors, nitrones, and nitroxides: past, present, and future. Med Res Rev. 2018;38(4):1159–1187.
  • Garland WA, Frenzel BD Doxorubicin adjuvants to reduce toxicity and methods for using the same. Google Patents. 2015.
  • Garland WA, Frenzel BD Doxorubicin adjuvants to reduce toxicity and methods for using the same. Google Patents. 2012.
  • Demeule M, Che C, Gabathuler R, et al. Etoposide and doxorubicin conjugates for drug delivery. Google Patents. 2014.
  • Demeule M, Che C, Gabathuler R, et al. Etoposide and doxorubicin conjugates for drug delivery. Google Patents. 2016.
  • Fiume L, Di Stefano G, Lanza M Process for the preparation of doxorubicin conjugates with lactosaminated human albumin. Google Patents. 2009.
  • Ruangwattanasuk O Doxorubicin derivatives and uses thereof. Google Patents. 2020.
  • Tomas Etrych K, Petr CPKU, Prague TM, Holesov, Blanka Rihova, Prague. Grafted macromolecular conugates of doxorubcn with anticanceractivity and method of ther preparation. Google Patents. 2013.
  • Xi J, Li M, Jing B, et al. Long-circulating amphiphilic doxorubicin for tumor mitochondria-specific targeting. ACS Appl Mater Interfaces. 2018 Dec 19;10(50):43482–43492.
  • Jose J, Kumar R, Harilal S, et al. Magnetic nanoparticles for hyperthermia in cancer treatment: an emerging tool. Environ Sci Pollut Res. 2020;27(16):19214–19225.
  • Raucher D, Bidwell III G, Priebe W, et al. Thermally-targeted delivery of medicaments including doxorubicin. Google Patents. 2012.
  • Tian B, Liu S, Wu S, et al. pH-responsive poly (acrylic acid)-gated mesoporous silica and its application in oral colon targeted drug delivery for doxorubicin. Colloids Surf B Biointerfaces. 2017;154:287–296.
  • Klinski E, Patel K, Pietrzynski G, et al. Doxorubicin formulations for anti-cancer use. Google Patents. 2012.
  • Johdo O, Nakao T, Yoshioka T Crystallization of doxorubicin hydrochloride. Google Patents. 2003.
  • Tasca E, Del Giudice A, Galantini L, et al. A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles. J Colloid Interface Sci. 2019;540:593–601.
  • Rashida A, Karmali B Method of reducing cardiaclevels of doxorubcn when given as orotate salt. Google Patents. 2012.
  • Martins JMA, Rabelo-Santos SH, do Amaral Westin MC, et al. Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis. BMC Cancer. 2020;20(1):1–11.
  • Kratz F Protein-binding doxorubicin peptide derivatives. Google Patents. 2010.
  • Mokhtari RB, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022.
  • Bissery M-C. Method of treating cancer with docetaxel and doxorubicin. Google Patents. 2011.
  • Rozencweig M, Goldfarb RH, Forenza S Non-pegylated liposomal doxorubicin triple combination therapy. Google Patents. 2011.
  • Gabizon A, Ohana P, Shmeeda H Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C. Google Patents. 2020.
  • Weissig V, Pettinger TK, Murdock N. Nanopharmaceuticals (part 1): products on the market. Int J Nanomedicine. 2014;9:4357–4373.
  • Hare JI, Lammers T, Ashford MB, et al. Challenges and strategies in anti-cancer nanomedicine development: an industry perspective. Adv Drug Deliv Rev. 2017 Jan 1;108:25–38.

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