Open Access Journal Article

Drug Transport via Nanocarrier for Liver Cancer Treatment

by Shafirah Hussein a  and  Jaffri Ruben b,*
Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia
Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience University, Putra 43400, Malaysia
Author to whom correspondence should be addressed.
Received: 15 May 2022 / Accepted: 5 June 2022 / Published: 13 June 2022


The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.

Copyright: © 2022 by Hussein and Ruben. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Show Figures

Share and Cite

ACS Style
Hussein, S.; Ruben, J. Drug Transport via Nanocarrier for Liver Cancer Treatment. Cancer Insight, 2022, 1, 5.
AMA Style
Hussein S, Ruben J. Drug Transport via Nanocarrier for Liver Cancer Treatment. Cancer Insight; 2022, 1(1):5.
Chicago/Turabian Style
Hussein, Shafirah; Ruben, Jaffri 2022. "Drug Transport via Nanocarrier for Liver Cancer Treatment" Cancer Insight 1, no.1: 5.
APA style
Hussein, S., & Ruben, J. (2022). Drug Transport via Nanocarrier for Liver Cancer Treatment. Cancer Insight, 1(1), 5.

Article Metrics

Article Access Statistics


  1. Jemal A, Bray F, Center M. Global cancer statistics. CA Cancer J. Clin. 2011; 61(2): 69–90. doi:10.3322/caac.20107
  2. Sia D, Villanueva A, Friedman SL, et al. Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 2017; 152: 745–761. doi:10.1053/j.gastro.2016.11.048
  3. Azzariti A, Iacobazzi RM, Fanizza E, et al. Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma. Nano. Res. 2017; 10(7): 2431–2448. doi:10.1007/s12274-017-1444-3
  4. Chabner BA, Roberts TG. Chemotherapy and the war on cancer. Nat. Rev . Cancer. 2005; 5(1): 65. doi:10.1038/nrc1529
  5. Kiparissides C, Kammona O. Nanoscale carriers for targeted delivery of drugs and therapeutic biomolecules. Can . J. Chem . Eng. 2013; 91(4): 638–651. doi:10.1002/cjce.v91.4
  6. Zhang N, Yu R, Cheng XY, et al. Visual targeted therapy of hepatic cancer using homing peptide modified calcium phosphate nanoparticles loading doxorubicin guided by T1 weighted MRI. Nanomedicine 2018. doi:10.1016/j.nano.2018.06.014
  7. Mishra N, Yadav NP, Rai VK, et al. Efficient hepatic delivery of drugs: Novel strategies and their significance. Biomed . Res . Int. 2013; 2013. doi:10.1155/2013/382184
  8. Lata S, Sharma G, Joshi M, et al. Role of nanotechnology in drug delivery. Int. J. Nanotechnol . Nanosci. 2017; 5: 1–29.
  9. Yang T, Lan Y, Cao M, et al. Glycyrrhetinic acid -conjugated polymeric prodrug micelles co -delivered with doxorubicin as combination therapy treatment for liver cancer. Colloids Surf . B. 2019. doi:10.1016/j.colsurfb.2018.11.082
  10. Barenholz YC. Doxil®—the firs t FDA-approved nano -drug: Lessons learned. J . Control. Release 2012; 160(2): 117 –134. doi:10.1016/j.jconrel.2012.03.020
  11. Wang B, Qiao W, Wang Y, et al. Cancer therapy based on nanomaterials and nanocarrier systems. J. Nanomater. 2010; 2010. doi:10.1155/2010/796303
  12. Masood F. Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Mater. Sci . Eng . C. 2016; 60: 569 –578. doi:10.1016/j.msec.2015.11.067
  13. Ye B, Zheng R, Ruan X, et al. Chitosan -coated doxorubicin nano -particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway. Biochem . Biophys . Res. Commun. 2018; 495(1): 414 –420. doi:10.1016/j.bbrc.2017.10.156
  14. Loutfy SA, El -Din HMA, Elberry MH, et al. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: In vitro liver cancer model. Adv . Nat . Sci. 2016; 7(3): 035008.
  15. Huang W, Wang W, Wang P, et al. Glycyrrhetinic acid -modified poly(ethylene glycol) -b -poly(γ -benzyl l -glutamate) micelles for liver targeting therapy. Acta Biomater. 2 010. doi:10.1016/j.actbio.2010.04.021
  16. Hanafy NAN, Quarta A, Ferraro MM, et al. Polymeric nano-micelles as novel cargo -carriers for LY2157299 liver cancer cells delivery. Int. J. Mol . Sci. 2018. doi:10.3390/ijms19030748
  17. Immordino ML, Dosio F, Cattel L. Stealth liposomes: R eview of the basic science, rationale, and clinical applications, existing and potential. Int. J. Nanomed. 2006; 1(3): 297–315.
  18. Wang J, Wu Z, Pan G, et al. Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody -conjugated immunoliposomes. Nanomed. 2018; 14(6): 1949–1961. doi:10.1016/j.nano.2017.09.012
  19. Persico M, Barbarisi M, Armenia E, et al. Chitosan- coated liposomes loaded with butyric acid demonstrate anticancer and anti- inflammatory activity in human hepatoma HepG2 cells. Oncol . Rep. 2018. doi:10.3892/or.2018.6932
  20. Noriega- Luna B, Godínez LA, Rodríguez FJ, et al. Applications of dendrimers in drug delivery agents, diagnosis, therapy, and detection. J . Nanomater. 2014; 2014: 1–19. doi:10.1155/2014/507273
  21. Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007; 2(12): 751 –760. doi:10.1038/nnano.2007.387
  22. Wojnarowicz J, Jesionowski T, Grześkowiak BF, et al. Dendrimer based theranostic nanostructures for combined chemo- and photothermal therapy of liver cancer cells in vitro . Colloids Surf. B. 2018; 173: 698 –708. doi:10.1016/j.colsurfb.2018.10.045
  23. Fu F, Wu Y, Zhu J, et al. Multifunctional lactobionic acid -modified dendrimers for targeted drug delivery to liver cancer cells: Investigating the role played by PEG spacer. ACS Appl . Mater . Interfaces. 2014; 6(18): 16416 –16425. doi:10.1021/am504849x
  24. Jain NK, Mody N, Tekade RK, et al. Glycyrrhizin conjugated dendrimer and multi -walled carbon nanotubes for liver specific delivery of doxorubicin. J . Nanosci . Nanotechnol. 2014; 15(2): 1088–1100. doi:10.1166/jnn.2015.9039
  25. Bondì ML, Botto C, Amore E, et al. Lipid nanocarriers containing sorafenib inhibit colonies formation in hu man hepatocarcinoma cells. Int. J. Pharm. 2015; 493(1–2): 75–85. doi:10.1016/j.ijpharm.2015.07.055
  26. Zhao X, Chen Q, Li Y, et al. Doxorubicin and curcumin co -delivery by lipid nanoparticles for enhanced treatment of diethylnitrosamine -induced hepatocellular carcinoma in mice. Eur. J. Pharm . Biopharm. 2015; 93: 27 –36. doi:10.1016/j.ejpb.2015.03.003
  27. Ebara M, Lee HJ, Aoyagi T, et al. Simultaneous drug and gene delivery from the biodegradable Poly( -caprolactone) nanofibers for the treatment of liver cancer. J . Nanosci . Nanotechnol. 2015. doi:10.1166/jnn.2015.11233
  28. Ji Y, Xiao Y, Xu L, et al. Drug -bearing supramolecular MMP inhibitor nanofibers for inhibition of metastasis and growth of liver cancer. Adv . Sci. 2018; 5: 1700867. doi:10.1002/advs.201700867
  29. Yang C, Yang C, Xu H, et al. Novel tumour-targeting, self- assembling peptide nanofiber as a carrier for effective curcumin delivery. Int. J. Nanomed . 2013; 197. doi:10.2147/IJN.S55875
  30. Zhang X, Deng F, Tian J, et al. Improving the drug delivery characteri stics of graphene oxide based polymer nanocomposites through the “one -pot” synthetic approach of single -electron transfer living radical polymerization. Appl. Surf. Sci. 2016; 378: 22–29. doi:10.1016/j.apsusc.2016.03.207
  31. Shim G, Kim MG, Park JY, et al. Graphene -based nanosheets for delivery of chemotherapeutics and biological drugs. Adv . Drug Deliv . Rev. 2016; 105: 205–227. doi:10.1016/j.addr.2016.04.004
  32. Yang H, Li H, Zhu L, et al. Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems. Carbohydr. Polym. 2016; 151: 812–820. doi:10.1016/j.carbpol.2016.06.024
  33. Yuan Y, Zhang Y, Liu B, et al. The effects of multifunctiona l MiR -122 -loaded graphene- gold composites on drug- resistant liver cancer. J . Nanobiotechnol . 2015; 13(1). doi:10.1186/s12951-015-0070-z
  34. Danhier F, Ansorena E, Silva JM, et al. PLGA -based nanoparticles: A n overview of biomedical applications. J . Control. Release 2012; 161(2): 505–522. doi:10.1016/j.jconrel.2012.01.043
  35. Gao DY, Lin TT, Sung YC, et al. CXCR4 -targeted lipid -coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer. Biomater . 2015; 67: 194 –203. doi:10.1016/j.biomaterials.2015.07.035
  36. Dangi R, Hurkat P, Jain A, et al. Targeting liver cancer via ASGP receptor using 5-FU-loaded surface- modified PLGA nanoparticles. J . Microencapsul. 2014; 31(5): 479–487. doi:10.3109/02652048.2013.879929
  37. Elhissi A, Ahm ed W, Hassan IU , et al. Carbon nanotubes in cancer therapy and drug delivery. J . Drug Deliv. 2012; 2012: 1 –10. doi:10.1155/2012/837327
  38. He H, Xiao D, Pham -Huy LA , et al. Carbon nanotubes used as nanocarriers in drug and biomolecule delivery. Drug Delivery Approaches Nanosyst. 2017; 163–212. doi:10.1201/9781315225371
  39. Qi X, Rui Y, Fan Y, et al. Galactosylated chitosan-grafted multiwall carbon nanotubes for pH -dependent sustained release and hepatic tumor -targeted delivery of doxorubicin in vivo. Colloids Surf . B. 2015; 133: 314 –322. doi:10.1016/j.colsurfb.2015.06.003
  40. Ji Z, Lin G, Lu Q, et al. Targeted therapy of SMMC -7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system. J . Colloid Interface Sci. 2012; 365(1): 143–149. doi:10.1016/j.jcis.2011.09.013
  41. Wang Y -XJ, Leung KC -F, Zhu X- M, et al. In vivo chemoembolization and magnetic resonance imaging of liver tumours by using iron oxide nanoshell/doxorubicin/poly(vinyl alcohol) hyb rid composites. Angew. Chem . Int. Ed. 2014; 53(19): 4812 –4815. doi:10.1002/anie.201402144
  42. Ye Y. Integrin t argeting for tumour optical i maging. Theragnostic . 2011; 1: 102. doi:10.7150/thno/v01p0102
  43. Zhang D, Wu M, Zeng Y, et al. Lipid micelles packaged with semiconducting polymer dots as simultaneous MRI/photoacoustic imaging and photodynamic/photothermal dual- modal therapeutic agents for liver cancer. J . Mater . Chem . B. 2016. doi:10.1039/c5tb01827g
  44. Liu Y, Yu D, Zhang N, et al. G adolinium -loaded polymeric nanoparticles modified with Anti- VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. Biomater. 2011; 32(22): 5167 –5176. doi:10.1016/j.biomaterials.2011.03.077
  45. Luo K, Liu G, He B, et al. Multifunctional gadolinium-based dendritic macromolecules as liver targeting imaging probes. Biomater . 2011; 32(10): 2575–2585. doi:10.1016/j.biomaterials.2010.12.049
  46. Park S, Kim JW, Jeong YY, et al. Drug -loaded superparamagnetic iron oxide nanoparticles for combined canc er imaging and therapy in vivo. Angew. Chem. Int. Ed. 2008; 47(29): 5362–5365. doi:10.1002/anie.200800857
  47. Wang YXJ. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging. World J. Gastroenterol. 2015; 21(47): 13400–13402. doi:10.3748/wjg.v21.i47.13400
  48. Arias JL, Reddy LH, Othman M, et al. Squalene based nanocomposites: a new platform for the design of multifunctional pharmaceutical theragnostic . ACS Nano. 2011; 5(2): 1513 –1521. doi:10.1021/nn1034197
  49. Olerile LD, Liu Y, Zhang B, et al. Near- infrared mediated quantum dots and paclitaxel co- loaded nanostructured lipid carriers for cancer theragnostic. Colloids Surf . B. 2017. doi:10.1016/j.colsurfb.2016.11.032
  50. Das RK, Mohapatra S. Highly luminescent, heteroatom -doped carbon quantum dots for ultrasensitive sensing of glucosamine and targeted imaging of liver cancer cells. J . Mater . Chem . B. 2017. doi:10.1039/c6tb03141b.
  51. Shao D, Li J, Pan Y, et al. Noninvasive theranostic imaging of HSV -TK/ GCV suicide gene therapy in liver cancer by folate -targeted quantum dot -based liposomes. Biomater . Sci. 2015; 3(6): 833–841. doi:10.1039/C5BM00077G
  52. Al-Jamal WT, Al -Jamal KT, Cakebread A, et al. Blood circulation and tissue biodistribution of lipid -quantum dot (L -QD) hybrid vesicles intravenously administered in mice. Bioconjug . Chem. 2009; 20: 1696 –1702. doi:10.1021/bc900047n
  53. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumours : improvement of tumor upt ake, lowering of systemic toxicity, and distinct tumour imaging in vivo. Adv Drug Deliv . Rev. 2013; 65(1): 71 –79. doi:10.1016/j.addr.2012.10.002
  54. Mohamed NK, Hamad MA, Hafez MZE, et al. Nanomedicine in management of hepatocellular carcinoma: challenges and opportunities. Int. J. Cancer. 2017; 140(7): 1475–1484. doi:10.1002/ijc.30517.
  55. Bae YH, Park K. Targeted drug delivery to tumours: M yths, reality and possibility. J . Control. Release 2011;153(3):198 –205. doi:10.1016/j.jconrel.2011.06.001
  56. Xiao K, Li Y, Luo J, et al. The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles. Biomater . 2011; 32(13): 3435–3446. doi:10.1016/j.biomaterials.2011.01.021
  57. Prabhu RH, Patravale VB, Joshi MD. Polymeric nanoparticles for targeted treatment in oncology: current insights. Int. J . Nanomedicine. 2015; 10: 1001 –1018. doi:10.2147/IJN.S56932
  58. Ferreira DDS, Lopes SCDA, Franco MS, et al. PH sensitive liposomes for drug delivery in cancer treatment. Ther . Deliv. 2013; 4(9): 1099 –1123. doi:10.4155/tde.13.80
  59. Xia Q, Li L, Zhao L. Silica nanoparticle -based dual -responsive nanoprodrug system for liver cancer therapy. Exp . Ther. Med. 2017; 14: 2071 –2077. doi:10.3892/etm.2017.4768
  60. Narayan R. Encyclopedia of Biomed ical Engineering. Elsevier; 2018.
  61. Walkey CD, Chan WCW. Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem . Soc . Rev. 2012; 41(7): 2780–2799. doi:10.1039/c1cs15233e
  62. Nkansah P, Antipas A, Lu Y, e t al. Development and evaluation of novel solid nanodispersion system for oral delivery of poorly water- soluble drugs. J . Control. Release 2013; 169(1–2): 150 –161. doi:10.1016/j.jconrel.2013.03.032
  63. Zhou F, Shang W, Yu X, et al. Glypican- 3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med. Res. Rev. 2018; 38(2): 741–767. doi:10.1002/med.21455
  64. Voutila J, Reebye V, Roberts TC, et al. Development and mechanism of small activating RNA targeting CEBPA, a novel therapeutic in clinical trials for liver cancer. Mol. Ther. 2017; 25(12): 2705–2714. doi:10.1016/j.ymthe.2017.07.018
  65. Kim Y, Jo M, Schmidt J, et al. Enhanced potency of GalNAc -conju gated antisense oligonucleotides in hepatocellular cancer models. Mol . Ther. 2019; 27(9): 1547–1557. doi:10.1016/j.ymthe.2019.06.009
  66. Harada T, Matsumoto S, Hirota S, et al. Chemically modified antisense oligonucleotide against ARL4C inhibits primary and me tastatic liver tumour growth. Mol. Cancer Ther. 2019; 18(3):602–612. doi:10.1158/1535 -7163.MCT- 18-0824