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Original Research

Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma

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Pages 8445-8467 | Published online: 29 Oct 2019

References

  • Prajapati SK, Jain A, Shrivastava C, Jain AK. Hyaluronic acid conjugated multi-walled carbon nanotubes for colon cancer targeting. Int J Biol Macromol. 2019;123:691–703. doi:10.1016/j.ijbiomac.2018.11.11630445095
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi:10.3322/caac.2155130620402
  • Mendez-Blanco C, Fondevila F, Garcia-Palomo A, Gonzalez-Gallego J, Mauriz JL. Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors. Exp Mol Med. 2018;50(10):134. doi:10.1038/s12276-018-0159-130315182
  • Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30. doi:10.3322/caac.2138728055103
  • Baecker A, Liu X, La Vecchia C, Zhang ZF. Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. Eur J Cancer Prev. 2018;27(3):205–212. doi:10.1097/CEJ.000000000000042829489473
  • Baig B, Halim SA, Farrukh A, Greish Y, Amin A. Current status of nanomaterial-based treatment for hepatocellular carcinoma. Biomed Pharmacother. 2019;116:108852. doi:10.1016/j.biopha.2019.10885230999152
  • McGuire S. World cancer report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016;7(2):418–419. doi:10.3945/an.116.01221126980827
  • Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, Nakatsura T. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2015;21(37):10573–10583. doi:10.3748/wjg.v21.i37.1057326457017
  • El-Houseini ME, Mohammed MS, Elshemey WM, Hussein TD, Desouky OS, Elsayed AA. Enhanced detection of hepatocellular carcinoma. Cancer Control. 2005;12(4):248–253. doi:10.1177/10732748050120040716258497
  • Elsadek B, Mansour A, Saleem T, Warnecke A, Kratz F. The antitumor activity of a lactosaminated albumin conjugate of doxorubicin in a chemically induced hepatocellular carcinoma rat model compared to sorafenib. Dig Liver Dis. 2017;49(2):213–222. doi:10.1016/j.dld.2016.10.00327825923
  • Hu B, Sun D, Sun C, et al. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma. Biochem Biophys Res Commun. 2015;468(4):525–532. doi:10.1016/j.bbrc.2015.10.03126482853
  • Lang L. FDA approves sorafenib for patients with inoperable liver cancer. Gastroenterology. 2008;134(2):379. doi:10.1053/j.gastro.2008.01.074
  • Yurdacan B, Egeli U, Guney Eskiler G, Eryilmaz IE, Cecener G, Tunca B. Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid. J Pharm Pharmacol. 2019;71:7. doi:10.1111/jphp.13097
  • Arrondeau J, Mir O, Boudou-Rouquette P, et al. Sorafenib exposure decreases over time in patients with hepatocellular carcinoma. Invest New Drugs. 2012;30(5):2046–2049. doi:10.1007/s10637-011-9764-822038662
  • Giglio V, Viale M, Bertone V, Maric I, Vaccarone R, Vecchio G. Cyclodextrin polymers as nanocarriers for sorafenib. Invest New Drugs. 2018;36(3):370–379. doi:10.1007/s10637-017-0538-929116478
  • Truong DH, Tran TH, Ramasamy T, et al. Preparation and characterization of solid dispersion using a novel amphiphilic copolymer to enhance dissolution and oral bioavailability of sorafenib. Powder Technol. 2015;283:260–265. doi:10.1016/j.powtec.2015.04.044
  • Truong D, Tran T, Ramasamy T, et al. Preparation and characterization of solid dispersion using a novel amphiphilic copolymer to enhance dissolution and oral bioavailability of sorafenib. Powder Technol. 2015;283(3):260–265. doi:10.1016/j.powtec.2015.04.044
  • Wang XQ, Fan JM, Liu YO, Zhao B, Jia ZR, Zhang Q. Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat. Int J Pharm. 2011;419(1–2):339–346. doi:10.1016/j.ijpharm.2011.08.00321843612
  • Zhang Z, Niu B, Chen J, et al. The use of lipid-coated nanodiamond to improve bioavailability and efficacy of sorafenib in resisting metastasis of gastric cancer. Biomaterials. 2014;35(15):4565–4572. doi:10.1016/j.biomaterials.2014.02.02424602567
  • Blanco E, Hsiao A, Mann AP, Landry MG, Meric-Bernstam F, Ferrari M. Nanomedicine in cancer therapy: innovative trends and prospects. Cancer Sci. 2011;102(7):1247–1252. doi:10.1111/j.1349-7006.2011.01941.x21447010
  • Marcazzan S, Varoni EM, Blanco E, Lodi G, Ferrari M. Nanomedicine, an emerging therapeutic strategy for oral cancer therapy. Oral Oncol. 2018;76:1–7. doi:10.1016/j.oraloncology.2017.11.01429290280
  • Scheinberg DA, Villa CH, Escorcia FE, McDevitt MR. Carbon Nanotubes Vol 2. Wiley-VCH Verlag GmbH & Co. KGaA; 2012.
  • He H, Pham-Huy L, Dramou P, Xiao D, Zuo P, Pham-Huy C. Carbon nanotubes: applications in pharmacy and medicine. Biomed Res Int. 2013;2013(2–3):1–12.
  • Kumar S, Prathibha D, Shankar N, Parthibarajan R, Mastyagiri L, Shankar M. Pharmaceutical application of carbon nanotube-mediated drug delivery system. Int J Pharm Sci Nanotech. 2012;5(3):1685–1696.
  • Usui Y, Haniu H, Tsuruoka S, Saito N. Carbon nanotubes innovate on medical technology. Med Chem. 2012;2(1):1–6. doi:10.4172/2161-0444.1000105
  • Choudhury H, Pandey M, Chin PX, et al. Transferrin receptors-targeting nanocarriers for efficient targeted delivery and transcytosis of drugs into the brain tumors: a review of recent advancements and emerging trends. Drug Deliv Transl Res. 2018;8(5):1545–1563. doi:10.1007/s13346-018-0552-229916012
  • Gao X, Guo L, Li J, Thu HE, Hussain Z. Nanomedicines guided nanoimaging probes and nanotherapeutics for early detection of lung cancer and abolishing pulmonary metastasis: critical appraisal of newer developments and challenges to clinical transition. J Control Release. 2018;292:29–57. doi:10.1016/j.jconrel.2018.10.02430359665
  • Mahajan S, Patharkar A, Kuche K, et al. Functionalized carbon nanotubes as emerging delivery system for the treatment of cancer. Int J Pharm. 2018;548(1):540–558. doi:10.1016/j.ijpharm.2018.07.02729997043
  • Singh B, Baburao C, Pispati V, et al. Carbon nanotubes. A novel drug delivery system. Int J of Res Pharm Chem. 2012;2(2):523–532.
  • Wang L-D, Zhou F-Y, Li X-M, et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies a susceptibility locus at PLCE1. Nat Genet. 2010;42:759. doi:10.1038/ng.64820729853
  • Khalili S, Tamim H, Khalili A, Rashidi MM. Unsteady convective heat and mass transfer in pseudoplastic nanofluid over a stretching wall. Adv Powder Technol. 2015;26(5):1319–1326. doi:10.1016/j.apt.2015.07.006
  • Wu W, Li R, Bian X, et al. Covalently combining carbon nanotubes with anticancer agent: preparation and antitumor activity. ACS Nano. 2009;3(9):2740–2750. doi:10.1021/nn900568619702292
  • Dhar S, Liu Z, Thomale J, Dai H, Lippard SJ. Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. J Am Chem Soc. 2008;130(34):11467–11476. doi:10.1021/ja803036e18661990
  • Hussain Z, Khan S, Imran M, Sohail M, Shah SWA, de Matas M. PEGylation: a promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution. Drug Deliv Transl Res. 2019. doi:10.1007/s13346-019-00631-4
  • Hashemzadeh H, Raissi H. The functionalization of carbon nanotubes to enhance the efficacy of the anticancer drug paclitaxel: a molecular dynamics simulation study. J Mol Model. 2017;23(8):222. doi:10.1007/s00894-017-3391-z28702805
  • Koupaei Malek S, Gabris MA, Hadi Jume B, et al. Adsorption and in vitro release study of curcumin form polyethyleneglycol functionalized multi walled carbon nanotube: kinetic and isotherm study. Daru. 2018.
  • Lay CL, Liu HQ, Tan HR, Liu Y. Delivery of paclitaxel by physically loading onto poly(ethylene glycol) (PEG)-graft-carbon nanotubes for potent cancer therapeutics. Nanotechnology. 2010;21(6):065101. doi:10.1088/0957-4484/21/6/06510120057024
  • Zhang HE, Henderson JM, Gorrell MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta (BBA). 2019;1865(5):993–1002. doi:10.1016/j.bbadis.2018.08.009
  • Abel EL, DiGiovanni J. 7 - environmental carcinogenesis In: Mendelsohn J, Gray JW, Howley PM, Israel MA, Thompson CB, editors. The Molecular Basis of Cancer. Fourth ed. Philadelphia: Content Repository Only!; 2015:103–128.e102.
  • Lohan S, Raza K, Mehta SK, Bhatti GK, Saini S, Singh B. Anti-Alzheimer’s potential of berberine using surface decorated multi-walled carbon nanotubes: a preclinical evidence. Int J Pharm. 2017;530(1):263–278. doi:10.1016/j.ijpharm.2017.07.08028774853
  • Zidan DW, Elmasry MS, Hassan WS, Shalaby AA. Utility of cremophor RH 40 as a micellar improvement for spectrofluorimetric estimation of sorafenib in pure form, commercial preparation, and human plasma. Luminescence. 2018;33(2):326–335. doi:10.1002/bio.341729124884
  • Kondo N, Iwao T, Hirai K, et al. Improved oral absorption of enteric coprecipitates of a poorly soluble drug. J Pharm Sci. 1994;83(4):566–570. doi:10.1002/jps.26008304258046616
  • Sobottka SB, Berger MR. Assessment of antineoplastic agents by MTT assay: partial underestimation of antiproliferative properties. Cancer Chemother Pharmacol. 1992;30(5):385–393. doi:10.1007/bf006899671505077
  • Zhang H, Zhang FM, Yan SJ. Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles. Int J Nanomed. 2012;7:2901–2910. doi:10.2147/IJN.S32415
  • Di Stefano G, Fiume L, Baglioni M, et al. Efficacy of doxorubicin coupled to lactosaminated albumin on rat hepatocellular carcinomas evaluated by ultrasound imaging. Dig Liver Dis. 2008;40(4):278–284. doi:10.1016/j.dld.2007.10.00818054847
  • Wilhelm S, Adnane L, Newell P, Villanueva A, Llovet J, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008;7(10):3129–3140. doi:10.1158/1535-7163.MCT-08-001318852116
  • Banchroft JD, Stevens A, Turner DR. Theory and Practice of Histoloicl Techniques. Fourth ed. New york, London, San Francisco, Tokyo: Churchil Livingstone; 1996.
  • Saleh IG, Ali Z, Hammad MA, et al. Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice. Hum Exp Toxicol. 2015;34(11):1180–1194. doi:10.1177/096032711557270725701483
  • Azqhandi MHA, Farahani BV, Dehghani N. Encapsulation of methotrexate and cyclophosphamide in interpolymer complexes formed between poly acrylic acid and poly ethylene glycol on multi-walled carbon nanotubes as drug delivery systems. Mater Sci Eng C Mater Biol Appl. 2017;79:841–847. doi:10.1016/j.msec.2017.05.08928629088
  • Grøndahl L, Lawrie G, Jejurikar A. 9 - Alginate-based drug delivery devices In: Sharma CP, editor. Biointegration of Medical Implant Materials. Woodhead Publishing; 2010:236–266.
  • Lopes M, Abrahim B, Veiga F, et al. Preparation methods and applications behind alginate-based particles. Expert Opin Drug Deliv. 2017;14(6):769–782. doi:10.1080/17425247.2016.121456427492462
  • Pasparakis G, Bouropoulos N. Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate-chitosan beads. Int J Pharm. 2006;323(1–2):34–42. doi:10.1016/j.ijpharm.2006.05.05416828245
  • Zhang L, Guo J, Peng X, Jin Y. Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin. J Appl Polym Sci. 2004;92(2):878–882. doi:10.1002/(ISSN)1097-4628
  • Zhang X, Hui Z, Wan D, et al. Alginate microsphere filled with carbon nanotube as drug carrier. Int J Biol Macromol. 2010;47(3):389–395. doi:10.1016/j.ijbiomac.2010.06.00320600269
  • Farahani B, Behbahani G, Javadi N. Functionalized multi walled carbon nanotubes as a carrier for doxorubicin: drug adsorption study and statistical optimization of drug loading by factorial design methodology. J Braz Chem Soc. 2016;27(4):694–705.
  • Habibizadeh M, Rostamizadeh K, Dalali N, Ramazani A. Preparation and characterization of PEGylated multiwall carbon nanotubes as covalently conjugated and non-covalent drug carrier: a comparative study. Mater Sci Eng C Mater Biol Appl. 2017;74(3):1–9. doi:10.1016/j.msec.2016.12.02328254271
  • Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217–223.20524422
  • Chen J, Chen S, Zhao X, Kuznetsova LV, Wong SS, Ojima I. Functionalized single-walled carbon nanotubes as rationally designed vehicles for tumor-targeted drug delivery. J Am Chem Soc. 2008;130(49):16778–16785. doi:10.1021/ja805570f19554734
  • Sajid MI, Jamshaid U, Jamshaid T, Zafar N, Fessi H, Elaissari A. Carbon nanotubes from synthesis to in vivo biomedical applications. Int J Pharm. 2016;501(1):278–299. doi:10.1016/j.ijpharm.2016.01.06426827920
  • Zakaria AB, Picaud F, Rattier T, et al. Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing. Nano Lett. 2015;15(2):891–895. doi:10.1021/nl503565t25584433
  • Tang S, Li Y. Sorafenib-loaded ligand-functionalized polymer-lipid hybrid nanoparticles for enhanced therapeutic effect against liver cancer. J Nanosci Nanotechnol. 2019;19(11):6866–6871. doi:10.1166/jnn.2019.1693631039838
  • Tang X, Chen L, Li A, et al. Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma. Drug Deliv. 2018;25(1):1484–1494. doi:10.1080/10717544.2018.147785929916268
  • Zhao Z-B, Long J, Zhao -Y-Y, et al. Adaptive immune cells are necessary for the enhanced therapeutic effect of sorafenib-loaded nanoparticles. Biomater Sci. 2018;6(4):893–900. doi:10.1039/c8bm00106e29512660
  • Bansal AK, Bansal M, Soni G, Bhatnagar D. Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. Chem Biol Interact. 2005;156(2–3):101–111. doi:10.1016/j.cbi.2005.08.00116144695
  • Di Stefano G, Fiume L, Baglioni M, et al. A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade. Liver Int. 2006;26(6):726–733. doi:10.1111/j.1478-3231.2006.01289.x16842330
  • Di Stefano G, Fiume L, Baglioni M, et al. Doxorubicin coupled to lactosaminated albumin: effect of heterogeneity in drug load on conjugate disposition and hepatocellular carcinoma uptake in rats. Eur J Pharm Sci. 2008;33(2):191–198. doi:10.1016/j.ejps.2007.11.00518201877
  • Fiume L, Bolondi L, Busi C, et al. Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine. J Hepatol. 2005;43(4):645–652. doi:10.1016/j.jhep.2005.02.04516023760
  • Sayed-Ahmed MM, Aleisa AM, Al-Rejaie SS, et al. Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxid Med Cell Longev. 2010;3(4):254–261. doi:10.4161/oxim.3.4.1271420972371
  • Sivaramakrishnan V, Shilpa PN, Praveen Kumar VR, Niranjali Devaraj S. Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinogenesis by a novel flavonol-Morin. Chem Biol Interact. 2008;171(1):79–88. doi:10.1016/j.cbi.2007.09.00317950263
  • Behne T, Copur MS. Biomarkers for hepatocellular carcinoma. Int J Hepatol. 2012;2012:859076. doi:10.1155/2012/96218322655201
  • Cheng J, Wang W, Zhang Y, et al. Prognostic role of pre-treatment serum AFP-L3% in hepatocellular carcinoma: systematic review and meta-analysis. PLoS One. 2014;9(1):e87011. doi:10.1371/journal.pone.008701124498011
  • Gan Y, Liang Q, Song X. Diagnostic value of alpha-L-fucosidase for hepatocellular carcinoma: a meta-analysis. Tumour Biol. 2014;35(5):3953–3960. doi:10.1007/s13277-013-1563-824395655
  • Jain D. Tissue diagnosis of hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(Suppl 3):S67–S73. doi:10.1016/j.jceh.2014.03.047
  • Lagana SM, Salomao M, Bao F, Moreira RK, Lefkowitch JH, Remotti HE. Utility of an immunohistochemical panel consisting of glypican-3, heat-shock protein-70, and glutamine synthetase in the distinction of low-grade hepatocellular carcinoma from hepatocellular adenoma. Appl Immunohistochem Mol Morphol. 2013;21(2):170–176. doi:10.1097/PAI.0b013e31825d527f22914605
  • Shi M, Huang Z, Yang Y, Zhao B. [Diagnostic value of serum Golgi protein-73 (GP73) combined with AFP-L3% in hepatocellular carcinoma: a meta-analysis]. Zhonghua Gan Zang Bing Za Zhi. 2015;23(3):189–193. doi:10.3760/cma.j.issn.1007-3418.2015.03.00725938831
  • Vora SR, Zheng H, Stadler ZK, Fuchs CS, Zhu AX. Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist. 2009;14(7):717–725. doi:10.1634/theoncologist.2009-003819581525
  • Wang NY, Wang C, Li W, et al. Prognostic value of serum AFP, AFP-L3, and GP73 in monitoring short-term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation. Asian Pac J Cancer Prev. 2014;15(4):1539–1544. doi:10.7314/apjcp.2014.15.4.153924641364
  • Kin M, Sata M, Ueno T, et al. Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism. J Hepatol. 1997;27(4):677–687. doi:10.1016/s0168-8278(97)80085-29365044
  • Lin D, Wu J. Hypoxia inducible factor in hepatocellular carcinoma: a therapeutic target. World J Gastroenterol. 2015;21(42):12171–12178. doi:10.3748/wjg.v21.i42.1217126576101
  • Luo D, Wang Z, Wu J, Jiang C, Wu J. The role of hypoxia inducible factor-1 in hepatocellular carcinoma. BioMed Research International. 2014;2014:409272.25101278
  • Mazzocca A, Fransvea E, Dituri F, Lupo L, Antonaci S, Giannelli G. Down-regulation of connective tissue growth factor by inhibition of transforming growth factor beta blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma. Hepatology. 2010;51(2):523–534. doi:10.1002/hep.2328519821534
  • Poon RT, Ng IO, Lau C, Yu WC, Fan ST, Wong J. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma. Am J Surg. 2001;182(3):298–304. doi:10.1016/s0002-9610(01)00708-511587697
  • Sandhu DS, Baichoo E, Roberts LR. Fibroblast growth factor signaling in liver carcinogenesis. Hepatology. 2014;59(3):1166–1173. doi:10.1002/hep.2667924716202
  • Xiang ZL, Zeng ZC, Fan J, et al. The expression of HIF-1alpha in primary hepatocellular carcinoma and its correlation with radiotherapy response and clinical outcome. Mol Biol Rep. 2012;39(2):2021–2029. doi:10.1007/s11033-011-0949-121647551
  • Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66(24):11851–11858. doi:10.1158/0008-5472.CAN-06-137717178882
  • Zhang CZ, Wang XD, Wang HW, Cai Y, Chao LQ. Sorafenib inhibits liver cancer growth by decreasing mTOR, AKT, and PI3K expression. J Buon. 2015;20(1):218–222.25778319
  • Afzal M, Kazmi I, Gupta G, Rahman M, Kimothi V, Anwar F. Preventive effect of Metformin against N-nitrosodiethylamine-initiated hepatocellular carcinoma in rats. Saudi Pharm J. 2012;20(4):365–370. doi:10.1016/j.jsps.2012.05.01223960811
  • Golla K, Bhaskar C, Ahmed F, Kondapi AK. A target-specific oral formulation of Doxorubicin-protein nanoparticles: efficacy and safety in hepatocellular cancer. J Cancer. 2013;4(8):644–652. doi:10.7150/jca.709324155776
  • Cao H, Wang Y, He X, et al. Codelivery of sorafenib and curcumin by directed self-assembled nanoparticles enhances therapeutic effect on hepatocellular carcinoma. Mol Pharm. 2015;12(3):922–931. doi:10.1021/mp500755j25622075
  • Ma L, Li G, Zhu H, et al. 2-Methoxyestradiol synergizes with sorafenib to suppress hepatocellular carcinoma by simultaneously dysregulating hypoxia-inducible factor-1 and −2. Cancer Lett. 2014;355(1):96–105. doi:10.1016/j.canlet.2014.09.01125218350
  • Sui J, Cui Y, Cai H, et al. Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma. Nanoscale. 2017;9(8):2755–2767. doi:10.1039/c6nr09639e28155940
  • Zhao R, Li T, Zheng G, Jiang K, Fan L, Shao J. Simultaneous inhibition of growth and metastasis of hepatocellular carcinoma by co-delivery of ursolic acid and sorafenib using lactobionic acid modified and pH-sensitive chitosan-conjugated mesoporous silica nanocomplex. Biomaterials. 2017;143:1–16. doi:10.1016/j.biomaterials.2017.07.03028755539