Skip to main content

Advertisement

SpringerLink
Log in

Strategies for Liposome Drug Delivery Systems to Improve Tumor Treatment Efficacy

  • Review Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

In the advancement of tumor therapy, in addition to the search for new antitumor compounds, the development of nano-drug delivery systems has opened up new pathways for tumor treatment by addressing some of the limitations of traditional drugs. Liposomes have received much attention for their high biocompatibility, low toxicity, high inclusivity, and improved drug bioavailability. They are one of the most studied nanocarriers, changing the size and surface characteristics of liposomes to better fit the tumor environment by taking advantage of the unique pathophysiology of tumors. They can also be designed as tumor targeting drug delivery vehicles for the precise delivery of active drugs into tumor cells. This paper reviews the current development of liposome formulations, summarizes the characterization methods of liposomes, and proposes strategies to improve the effectiveness of tumor treatment. Finally, it provides an outlook on the challenges and future directions of the field.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.

    Article  PubMed  Google Scholar 

  3. Arranja AG, Pathak V, Lammers T, Shi Y. Tumor-targeted nanomedicines for cancer theranostics. Pharmacol Res. 2017;115:87–95. https://doi.org/10.1016/j.phrs.2016.11.014.

    Article  CAS  PubMed  Google Scholar 

  4. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238–52.

    Article  CAS  PubMed  Google Scholar 

  5. Monteiro N, Martins A, Reis RL, Neves NM. Liposomes in tissue engineering and regenerative medicine. J R Soc Interface. 2014;11(101). https://doi.org/10.1098/rsif.2014.0459.

  6. Briuglia ML, Rotella C, McFarlane A, Lamprou DA. Influence of cholesterol on liposome stability and on in vitro drug release. Drug Deliv Transl Res. 2015;5(3):231–42. https://doi.org/10.1007/s13346-015-0220-8.

    Article  CAS  PubMed  Google Scholar 

  7. Liu WL, Hou YY, Jin YY, Wang YP, Xu XK, Han JZ. Research progress on liposomes: Application in food, digestion behavior and absorption mechanism. Trends Food Sci Technol. 2020;104:177–89. https://doi.org/10.1016/j.tifs.2020.08.012.

    Article  CAS  Google Scholar 

  8. Mathiyazhakan M, Wiraja C, Xu C. A concise review of gold nanoparticles-based photo-responsive liposomes for controlled drug delivery. Nano Lett. 2018;10(1). https://doi.org/10.1007/s40820-017-0166-0.

  9. He H, Yi L, Qi J, Zhu Q, Chen Z, Wei W. Adapting liposomes for oral drug delivery. Acta Pharm Sin B. 2019;9(01):46–58. https://doi.org/10.1016/j.apsb.2018.06.005.

    Article  Google Scholar 

  10. Yan W, Leung SSY, To KKW. Updates on the use of liposomes for active tumor targeting in cancer therapy. Nanomedicine. 2020;15(3):303–18. https://doi.org/10.2217/nnm-2019-0308.

    Article  CAS  PubMed  Google Scholar 

  11. Lee W, Im H-J. Theranostics based on liposome: Looking back and forward. Nucl Med Mol Imaging. 2019;53(4):242–6. https://doi.org/10.1007/s13139-019-00603-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. La-Beck NM, Liu X, Wood LM. Harnessing liposome interactions with the immune system for the next breakthrough in cancer drug delivery. Front Pharmacol. 2019;10. https://doi.org/10.3389/fphar.2019.00220.

  13. Crommelin DJA, Storm G. Liposomes: From the bench to the bed. J Liposome Res. 2003;13(1):33–6. https://doi.org/10.1081/LPR-120017488.

    Article  PubMed  Google Scholar 

  14. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2). https://doi.org/10.3390/pharmaceutics10020057.

  15. Peretz Damari S, Shamrakov D, Varenik M, Koren E, Nativ-Roth E, Barenholz Y, Regev O. Practical aspects in size and morphology characterization of drug-loaded nano-liposomes. Int J Pharm. 2018;547(1):648–55. https://doi.org/10.1016/j.ijpharm.2018.06.037.

    Article  CAS  PubMed  Google Scholar 

  16. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99. https://doi.org/10.2147/IJN.S68861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang X, Li Y, Shen S, Lee S, Dou H. Field-flow fractionation: a gentle separation and characterization technique in biomedicine. TrAC Trends Anal Chem. 2018;108:231–8. https://doi.org/10.1016/j.trac.2018.09.005.

    Article  CAS  Google Scholar 

  18. Guimaraes D, Cavaco-Paulo A, Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm. 2021;601:120571. https://doi.org/10.1016/j.ijpharm.2021.120571.

    Article  CAS  PubMed  Google Scholar 

  19. Maulucci G, De Spirito M, Arcovito G, Boffi F, Castellano AC, Briganti G. Particle size distribution in DMPC vesicles solutions undergoing different sonication times. Biophys J. 2005;88(5):3545–50. https://doi.org/10.1529/biophysj.104.048876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wagner A, Voraueruhl K. Liposome technology for industrial purposes. J Drug Del. 2011;2011:591325. https://doi.org/10.1155/2011/591325.

    Article  CAS  Google Scholar 

  21. Ong SGM, Chitneni M, Lee KS, Ming LC, Yuen KH. Evaluation of extrusion technique for nanosizing liposomes. Pharmaceutics. 2016;8(4). https://doi.org/10.3390/pharmaceutics8040036.

  22. Kuang Y, Liu J, Liu Z, Zhuo R. Cholesterol-based anionic long-circulating cisplatin liposomes with reduced renal toxicity. Biomaterials. 2012;33(5):1596–606. https://doi.org/10.1016/j.biomaterials.2011.10.081.

    Article  CAS  PubMed  Google Scholar 

  23. Inoh Y, Hirose T, Yokoi A, Yokawa S, Furuno T. Effects of lipid composition in cationic liposomes on suppression of mast cell activation. Chem Phys Lipids. 2020;231:104948. https://doi.org/10.1016/j.chemphyslip.2020.104948.

    Article  CAS  PubMed  Google Scholar 

  24. Dadashzadeh S, Mirahmadi N, Babaei MH, Vali AM. Peritoneal retention of liposomes: effects of lipid composition, PEG coating and liposome charge. J Control Release. 2010;148(2):177–86. https://doi.org/10.1016/j.jconrel.2010.08.026.

    Article  CAS  PubMed  Google Scholar 

  25. Beg S, Almalki WH, Khatoon F, Alharbi KS, Alghamdi S, Akhter MH, Khalilullah H, Baothman AA, Hafeez A, Rahman M, Akhter S, Choudhry H. Lipid/polymer-based nanocomplexes in nucleic acid delivery as cancer vaccines. Drug Discov Today. 2021;26(8):1891–903. https://doi.org/10.1016/j.drudis.2021.02.013.

    Article  CAS  PubMed  Google Scholar 

  26. Ong SGM, Ming LC, Lee KS, Yuen KH. Influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Pharmaceutics. 2016;8(3). https://doi.org/10.3390/pharmaceutics8030025.

  27. Pattni BS, Chupin VV, Torchilin VP. New developments in liposomal drug delivery. Chem Rev. 2015;115:10938–66. https://doi.org/10.1021/acs.chemrev.5b00046.

    Article  CAS  PubMed  Google Scholar 

  28. Laouini A, Jaafar-Maalej C, Limayem-Blouza I, Sfar S, Charcosset C, Fessi H. Preparation, characterization and applications of liposomes: state of the art. J Colloid Sci Biotechnol. 2012;1(2):147–68. https://doi.org/10.1166/jcsb.2012.1020.

    Article  CAS  Google Scholar 

  29. Xu D, Xie J, Feng X, Zhang X, Ren Z, Zheng Y, Yang J. Preparation and evaluation of a Rubropunctatin-loaded liposome anticancer drug carrier. RSC Adv. 2020;10(17):10352–60. https://doi.org/10.1039/c9ra10390b.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang M, Zhao T, Liu T, et al. Ursolic acid liposomes with chitosan modification: promising antitumor drug delivery and efficacy. Mater Sci Eng C. 2017;71:1231–40. https://doi.org/10.1016/j.msec.2016.11.014.

    Article  CAS  Google Scholar 

  31. SanjaPetrović AT, SašaSavić VN, LjubišaNikolić SS. Sulfanilamide in solution and liposome vesicles; in vitro release and UV-stability studies. Saudi Pharm J. 2017;25(8):1194–200. https://doi.org/10.1016/j.jsps.2017.09.003.

    Article  Google Scholar 

  32. Tang J, Srinivasan S, Yuan W, Ming R, Liu Y, Dai Z, Noble CO, Hayes ME, Zheng N, Jiang W, Szoka FC, Schwendeman A. Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome. Eur J Pharm Biopharm. 2019;134:107–16. https://doi.org/10.1016/j.ejpb.2018.11.010.

    Article  CAS  PubMed  Google Scholar 

  33. Dan N. Drug release through liposome pores. Colloids Surf B: Biointerfaces. 2015;126:80–6. https://doi.org/10.1016/j.colsurfb.2014.11.042.

    Article  CAS  PubMed  Google Scholar 

  34. Xie Y, Shao N, Jin Y, Zhang L, Jiang H, Xiong N, Su F, Xu H. Determination of non-liposomal and liposomal doxorubicin in plasma by LC–MS/MS coupled with an effective solid phase extraction: In comparison with ultrafiltration technique and application to a pharmacokinetic study. J Chromatogr B. 2018;1072:149–60. https://doi.org/10.1016/j.jchromb.2017.11.020.

    Article  CAS  Google Scholar 

  35. Su C, Yang H, Sun H, Fawcett JP, Sun D, Gu J. Bioanalysis of free and liposomal Amphotericin B in rat plasma using solid phase extraction and protein precipitation followed by LC-MS/MS. J Pharm Biomed Anal. 2018;158:288–93. https://doi.org/10.1016/j.jpba.2018.06.014.

    Article  CAS  PubMed  Google Scholar 

  36. Luo M, Zhang R, Liu L, Chi J, Zhang M. Preparation, stability and antioxidant capacity of nano liposomes loaded with procyandins from lychee pericarp. J Food Eng. 2020;284:110065. https://doi.org/10.1016/j.jfoodeng.2020.110065.

    Article  CAS  Google Scholar 

  37. Liu Y, Liu D, Zhu L, Gan Q, Le X. Temperature-dependent structure stability and in vitro release of chitosan-coated curcumin liposome. Food Res Int. 2015;74:97–105. https://doi.org/10.1016/j.foodres.2015.04.024.

    Article  CAS  PubMed  Google Scholar 

  38. Rahnfeld L, Thamm J, Steiniger F, Hoogevest PV, Luciani P. Study on the in situ aggregation of liposomes with negatively charged phospholipids for use as injectable depot formulation. Colloids Surf B: Biointerfaces. 2018;168:10–7. https://doi.org/10.1016/j.colsurfb.2018.02.023.

    Article  CAS  PubMed  Google Scholar 

  39. Maeda H. Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J Control Release. 2012;164(2):138–44. https://doi.org/10.1016/j.jconrel.2012.04.038.

    Article  CAS  PubMed  Google Scholar 

  40. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71–9. https://doi.org/10.1016/j.addr.2012.10.002.

    Article  CAS  PubMed  Google Scholar 

  41. Egusquiaguirre SP, Igartua M, Hernández RM, Pedraz JL. Nanoparticle delivery systems for cancer therapy: Advances in clinical and preclinical research. Clin Transl Oncol. 2012;14(2):83–93. https://doi.org/10.1007/s12094-012-0766-6.

    Article  CAS  PubMed  Google Scholar 

  42. Noble GT, Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. Ligand-targeted liposome design: challenges and fundamental considerations. Trends Biotechnol. 2014;32(1):32–45. https://doi.org/10.1016/j.tibtech.2013.09.007.

    Article  CAS  PubMed  Google Scholar 

  43. Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats. Nanomedicine. 2008;3(5):703–17. https://doi.org/10.2217/17435889.3.5.703.

    Article  CAS  PubMed  Google Scholar 

  44. Moghimi SM, Farhangrazi ZS. Nanomedicine and the complement paradigm. Nanomedicine. 2013;9(4):458–60. https://doi.org/10.1016/j.nano.2013.02.011.

    Article  CAS  PubMed  Google Scholar 

  45. Saraf S, Jain A, Tiwari A, Verma A, Panda PK, Jain SK. Advances in liposomal drug delivery to cancer: an overview. J Drug Delivci Technol. 2020;56:101549. https://doi.org/10.1016/j.jddst.2020.101549.

    Article  CAS  Google Scholar 

  46. Maruyama K. Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev. 2011;63(3):161–9. https://doi.org/10.1016/j.addr.2010.09.003.

    Article  CAS  PubMed  Google Scholar 

  47. Ding N, Wang YX, Wang XL, Chu W, Yin T, Gou JX, He H, Zhang Y, Wang Y, Tang X. Improving plasma stability and antitumor effect of gemcitabine via PEGylated liposome prepared by active drug loading. J Drug Delivci Technol. 2020;57:101538. https://doi.org/10.1016/j.jddst.2020.101538.

    Article  CAS  Google Scholar 

  48. Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. A systematic analysis of peptide linker length and liposomal polyethylene glycol coating on cellular uptake of peptide-targeted liposomes. ACS Nano. 2013;7(4):2935–47. https://doi.org/10.1021/nn305663e.

    Article  CAS  PubMed  Google Scholar 

  49. Stefanick JF, Ashley JD, Bilgicer B. Enhanced cellular uptake of peptide-targeted nanoparticles through increased peptide hydrophilicity and optimized ethylene glycol peptide-linker length. ACS Nano. 2013;7(9):8115–27. https://doi.org/10.1021/nn4033954.

    Article  CAS  PubMed  Google Scholar 

  50. Środa K, Rydlewski J, Langner M, Kozubek A, Grzybek M, Sikorski AF. Repeated injections of PEG-PE liposomes generate anti-PEG antibodies. Cell Mol Biol Lett. 2005;10:37–47. https://doi.org/10.1109/ICASSP.2011.5946843.

    Article  PubMed  Google Scholar 

  51. Caliceti P, Veronese FM. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)–protein conjugates. Adv Drug Deliv Rev. 2003;55(10):1261–77. https://doi.org/10.1016/S0169-409X(03)00108-X.

    Article  CAS  PubMed  Google Scholar 

  52. Li Y, Liu R, Yang J, Shi Y, Ma G, Zhang Z, Zhang X. Enhanced retention and anti-tumor efficacy of liposomes by changing their cellular uptake and pharmacokinetics behavior. Biomaterials. 2015;41:1–14. https://doi.org/10.1016/j.biomaterials.2014.11.010.

    Article  CAS  PubMed  Google Scholar 

  53. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60(15):1615–26. https://doi.org/10.1016/j.addr.2008.08.005.

    Article  CAS  PubMed  Google Scholar 

  54. Wang W, Shao A, Zhang N, Fang J, Ruan JJ, Ruan BH. Cationic polymethacrylate-modified liposomes significantly enhanced doxorubicin delivery and antitumor activity. Sci Rep. 2017;7. https://doi.org/10.1038/srep43036.

  55. Muhammad R, Muhammad R, Xue Z, Lin C, Ka W, Chen X, et al. Surface functionalization and targeting strategies of liposomes in solid tumor therapy: A review. Int J Mol Sci. 2018;19(1). https://doi.org/10.3390/ijms19010195.

  56. Jhaveri A, Deshpande P, Pattni B, Torchilin V. Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. J Control Release Offi J Control Release Soc. 2018;227:89–101. https://doi.org/10.1016/j.jconrel.2018.03.006.

    Article  CAS  Google Scholar 

  57. Jang JH, Kim YJ, Kim H, Kim SC, Cho JH. Buforin IIb induces endoplasmic reticulum stress-mediated apoptosis in HeLa cells. Peptides. 2015;69:144–9. https://doi.org/10.1016/j.peptides.2015.04.024.

    Article  CAS  PubMed  Google Scholar 

  58. Zhang X, Lin C, Lu A, Lin G, Chen H, Liu Q, Yang Z, Zhang H. Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma. Drug Deliv. 2017;24(1):986–98. https://doi.org/10.1080/10717544.2017.1340361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dosio F, Arpicco S, Stella B, Fattal E. Hyaluronic acid for anticancer drug and nucleic acid delivery. Adv Drug Deliv Rev. 2016;97:204–36. https://doi.org/10.1016/j.addr.2015.11.011.

    Article  CAS  PubMed  Google Scholar 

  60. Wang J, Liu D, Guan S, Zhu WQ, Fan L, Zhang Q, Cai D. Hyaluronic acid-modified liposomal honokiol nanocarrier: enhance anti-metastasis and antitumor efficacy against breast cancer. Carbohydr Polym. 2020;235:115981. https://doi.org/10.1016/j.carbpol.2020.115981.

    Article  CAS  PubMed  Google Scholar 

  61. Catuogno S, Esposito CL, de Franciscis V. Aptamer-mediated targeted delivery of therapeutics: an update. Pharmaceuticals (Basel). 2016;9(4). https://doi.org/10.3390/ph9040069.

  62. Li X, Wu X, Yang H, Li L, Ye Z, Rao Y. A nuclear targeted Dox-aptamer loaded liposome delivery platform for the circumvention of drug resistance in breast cancer. Biomed Pharmacother. 2019;117:109072. https://doi.org/10.1016/j.biopha.2019.109072.

    Article  CAS  PubMed  Google Scholar 

  63. Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, Dorkoosh FA, Handali S. Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil. Eur J Pharm Sci. 2018;114:166–74. https://doi.org/10.1016/j.ejps.2017.12.011.

    Article  CAS  PubMed  Google Scholar 

  64. Li LL, An XQ, Yan XJ. Folate-polydiacetylene-liposome for tumor targeted drug delivery and fluorescent tracing. Colloids Surf B-Biointerfaces. 2015;134:235–9. https://doi.org/10.1016/j.colsurfb.2015.07.008.

    Article  CAS  PubMed  Google Scholar 

  65. Huang MY, Pu YC, Peng Y, Fu QY, Guo L, Wu Y, et al. Biotin and glucose dual-targeting, ligand-modified liposomes promote breast tumor-specific drug delivery. Bioorg Med Chem Lett. 2020;30(12). https://doi.org/10.1016/j.bmcl.2020.127151.

  66. Yamada Y, Furukawa R, Harashima H. A dual-ligand liposomal system composed of a cell-penetrating peptide and a mitochondrial RNA aptamer synergistically facilitates cellular uptake and mitochondrial targeting. J Pharm Sci. 2016;105(5):1705–13. https://doi.org/10.1016/j.xphs.2016.03.002.

    Article  CAS  PubMed  Google Scholar 

  67. Han W, Yin G, Pu X, Chen X, Liao X, Huang Z. Glioma targeted delivery strategy of doxorubicin-loaded liposomes by dual-ligand modification. J Biomater Sci Polym Ed. 2017;28(15):1695–712. https://doi.org/10.1080/09205063.2017.1348739.

    Article  CAS  PubMed  Google Scholar 

  68. Deshpande P, Jhaveri A, Pattni B, Biswas S, Torchilin V. Transferrin and octaarginine modified dual-functional liposomes with improved cancer cell targeting and enhanced intracellular delivery for the treatment of ovarian cancer. Drug Del. 2018;25(1):517–32. https://doi.org/10.1080/10717544.2018.1435747.

    Article  CAS  Google Scholar 

  69. Li M, Shi K, Tang X, Wei J, Cun X, Long Y, Zhang Z, He Q. Synergistic tumor microenvironment targeting and blood-brain barrier penetration via a pH-responsive dual-ligand strategy for enhanced breast cancer and brain metastasis therapy. Nanomedicine. 2018;14(6):1833–43. https://doi.org/10.1016/j.nano.2018.05.008.

    Article  CAS  PubMed  Google Scholar 

  70. Lin C, Zhang X, Chen H, Bian Z, Zhang G, Riaz MK, Tyagi D, Lin G, Zhang Y, Wang J, Lu A, Yang Z. Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide. Drug Deliv. 2018;25(1):256–66. https://doi.org/10.1080/10717544.2018.1425777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhang J, Xiao X, Zhu J, Gao Z, Lai X, Zhu X, Mao G. Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy. Int J Nanomedicine. 2018;13:3039–51. https://doi.org/10.2147/IJN.S161163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Stefanick JF, Omstead DT, Kiziltepe T, Bilgicer B. Dual-receptor targeted strategy in nanoparticle design achieves tumor cell selectivity through cooperativity. Nanoscale. 2019;11(10):4414–27. https://doi.org/10.1039/c8nr09431d.

    Article  CAS  PubMed  Google Scholar 

  73. Yoon HY, Yang HM, Kim CH, Goo YT, Hwang GY, Chang IH, et al. Enhanced intracellular delivery of BCG cell wall skeleton into bladder cancer cells using liposomes functionalized with folic acid and Pep-1 peptide. Pharmaceutics. 2019;11(12). https://doi.org/10.3390/pharmaceutics11120652.

  74. Li X, Diao W, Xue H, Wu F, Wang W, Jiang B, Bai J, Lian B, Feng W, Sun T, Yu W, Wu J, Qu M, Wang Y, Gao Z. Improved efficacy of doxorubicin delivery by a novel dual-ligand-modified liposome in hepatocellular carcinoma. Cancer Lett. 2020;489:163–73. https://doi.org/10.1016/j.canlet.2020.06.017.

    Article  CAS  PubMed  Google Scholar 

  75. Dos Santos RB, Lakkadwala S, Kanekiyo T, Singh J. Dual-modified liposome for targeted and enhanced gene delivery into mice brain. J Pharmacol Exp Ther. 2020;374(3):354–65. https://doi.org/10.1124/jpet.119.264127.

    Article  CAS  Google Scholar 

  76. Belfiore L, Saunders DN, Ranson M, Thurecht KJ, Storm G, Vine KL. Towards clinical translation of ligand-functionalized liposomes in targeted cancer therapy: challenges and opportunities. J Control Release. 2018;277:1–13. https://doi.org/10.1016/j.jconrel.2018.02.040.

    Article  CAS  PubMed  Google Scholar 

  77. Belfiore L, Spenkelink LM, Ranson M, van Oijen AM, Vine KL. Quantification of ligand density and stoichiometry on the surface of liposomes using single-molecule fluorescence imaging. J Control Release. 2018;278:80–6. https://doi.org/10.1016/j.jconrel.2018.03.022.

    Article  CAS  PubMed  Google Scholar 

  78. Qiu L, Xu Y. Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes. Int J Nanomedicine. 2015;10:4225–37. https://doi.org/10.2147/IJN.S84555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hu C-MJ, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol. 2012;83(8):1104–11. https://doi.org/10.1016/j.bcp.2012.01.008.

    Article  CAS  PubMed  Google Scholar 

  80. Sen K, Banerjee S, Mandal M. Dual drug loaded liposome bearing apigenin and 5-Fluorouracil for synergistic therapeutic efficacy in colorectal cancer. Colloids Surf B: Biointerfaces. 2019;180:9–22. https://doi.org/10.1016/j.colsurfb.2019.04.035.

    Article  CAS  PubMed  Google Scholar 

  81. Zeinali M, Abbaspour-Ravasjani S, Ghorbani M, Babazadeh A, Soltanfam T, Santos AC, Hamishehkar H, Hamblin MR. Nanovehicles for co-delivery of anticancer agents. Drug Discov Today. 2020;25(8):1416–30. https://doi.org/10.1016/j.drudis.2020.06.027.

    Article  CAS  PubMed  Google Scholar 

  82. Soliman MS, Moin A, Hussain T, Gowda DV, Dixit SR, Abu Lila AS. Development and optimization of dual drug-loaded nanoparticles for the potent anticancer effect on renal carcinoma. J Drug Delivci Technol. 2020;59:101846. https://doi.org/10.1016/j.jddst.2020.101846.

    Article  CAS  Google Scholar 

  83. Rolle F, Bincoletto V, Gazzano E, Rolando B, Lollo G, Stella B, Riganti C, Arpicco S. Coencapsulation of disulfiram and doxorubicin in liposomes strongly reverses multidrug resistance in breast cancer cells. Int J Pharm. 2020;580:119191. https://doi.org/10.1016/j.ijpharm.2020.119191.

    Article  CAS  PubMed  Google Scholar 

  84. Guo P, Pi C, Zhao S, Fu S, Yang H, Zheng X, Zhang X, Zhao L, Wei Y. Oral co-delivery nanoemulsion of 5-fluorouracil and curcumin for synergistic effects against liver cancer. Expert Opin Drug Del. 2020;17(10):1473–84. https://doi.org/10.1080/17425247.2020.1796629.

    Article  CAS  Google Scholar 

  85. Patel G, Thakur NS, Kushwah V, Patil MD, Nile SH, Jain S, Banerjee UC, Kai G. Liposomal delivery of mycophenolic acid with quercetin for improved breast cancer therapy in SD rats. Front Bioeng Biotechnol. 2020;8. https://doi.org/10.3389/fbioe.2020.00631.

  86. Shim G, Lee S, Choi J, Lee S, Kim CW, Oh YK. Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for synergistic potentiation of antitumor activity. Pharm Res. 2014;31(8):2178–85. https://doi.org/10.1007/s11095-014-1317-3.

    Article  CAS  PubMed  Google Scholar 

  87. Ravar F, Saadat E, Kelishadi PD, Dorkoosh FA. Liposomal formulation for co-delivery of paclitaxel and lapatinib, preparation, characterization and optimization. J Liposome Res. 2015;26(3):175–87. https://doi.org/10.3109/08982104.2015.1070174.

    Article  CAS  PubMed  Google Scholar 

  88. Ruttala HB, Ko YT. Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy. Colloids Surf B: Biointerfaces. 2015;128:419–26. https://doi.org/10.1016/j.colsurfb.2015.02.040.

    Article  CAS  PubMed  Google Scholar 

  89. Zhang Y, Zhai MF, Chen ZJ, Han XY, Yu FL, Li ZP, Xie X, Han C, Yu L, Yang Y, Mei X. Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma. Drug Del. 2017;24(1):1045–55. https://doi.org/10.1080/10717544.2017.1344334.

    Article  CAS  Google Scholar 

  90. Xue-Jia K, Hui-Yuan W, Hui-Ge P, et al. Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy. Acta Pharmacol Sin. 2017:885–96. https://doi.org/10.1038/aps.2017.10.

  91. Cheng Y, Zhao P, Wu S, Yang T, Chen Y, Zhang X, He C, Zheng C, Li K, Ma X, Xiang G. Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma. Int J Pharm. 2018;545(1-2):261–73. https://doi.org/10.1016/j.ijpharm.2018.05.007.

    Article  CAS  PubMed  Google Scholar 

  92. Zhang R, Zhang Y, Zhang Y, Wang X, Gao X, Liu Y, Zhang X, He Z, Wang D, Wang Y. Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than DoxilⓇ. Asian J Pharm Sci. 2020;15(3):385–96. https://doi.org/10.1016/j.ajps.2019.04.007.

    Article  PubMed  Google Scholar 

  93. Song M, Liang Y, Li K, Zhang J, Zhang N, Tian B, Han J. Hyaluronic acid modified liposomes for targeted delivery of doxorubicin and paclitaxel to CD44 overexpressing tumor cells with improved dual-drugs synergistic effect. J Drug Delivci Technol. 2019;53:101179. https://doi.org/10.1016/j.jddst.2019.101179.

    Article  CAS  Google Scholar 

  94. Mishra H, Mishra PK, Iqbal Z, Jaggi M, Madaan A, Bhuyan K, et al. Co-delivery of eugenol and dacarbazine by hyaluronic acid-coated liposomes for targeted inhibition of survivin in treatment of resistant metastatic melanoma. Pharmaceutics. 2019;11(4). https://doi.org/10.3390/pharmaceutics11040163.

  95. Anup J, Manoj NK, Sriravali K, Krishna V. Temperature-sensitive liposomes for codelivery of tamoxifen and imatinib for synergistic breast cancer treatment. J Liposome Res. 2018;29:1–32. https://doi.org/10.1080/08982104.2018.1502315.

    Article  CAS  Google Scholar 

  96. Vu MT, Nguyen DTD, Nguyen NH, Le VT, Dao TN, Nguyen TH, et al. Development, characterization and in vitro evaluation of paclitaxel and anastrozole co-loaded liposome. Processes. 2020;8(9). https://doi.org/10.3390/pr8091110.

  97. Yuba E. Development of functional liposomes by modification of stimuli-responsive materials and their biomedical applications. J Mater Chem B. 2020;8(6):1093–107. https://doi.org/10.1039/C9TB02470K.

    Article  CAS  PubMed  Google Scholar 

  98. Lee Y, Thompson DH. Stimuli-responsive liposomes for drug delivery. Wiley Interdisc Rev: Nanomedicine Nanobiotechnol. 2017;9(5). https://doi.org/10.1002/wnan.1450.

  99. Zhao Y, Ren W, Zhong T, Zhang S, Huang D, Guo Y, Yao X, Wang C, Zhang WQ, Zhang X, Zhang Q. Tumor-specific pH-responsive peptide-modified pH-sensitive liposomes containing doxorubicin for enhancing glioma targeting and anti-tumor activity. J Control Release. 2016;222:56–66. https://doi.org/10.1016/j.jconrel.2015.12.006.

    Article  CAS  PubMed  Google Scholar 

  100. Burks SR, Legenzov EA, Martin EW, Li C, Lu W, Kao JP. Co-encapsulating the fusogenic peptide INF7 and molecular imaging probes in liposomes increases intracellular signal and probe retention. PLoS One. 2015;10(3). https://doi.org/10.1371/journal.pone.0120982.

  101. Reja RM, Khan M, Singh SK, Misra R, Shiras A, Gopi HN. pH sensitive coiled coils: a strategy for enhanced liposomal drug delivery. Nanoscale. 2016;8(9):5139–45. https://doi.org/10.1039/c5nr07734f.

    Article  CAS  PubMed  Google Scholar 

  102. van Elk M, van den Dikkenberg JB, Storm G, Hennink WE, Vermonden T, Heger M. Preclinical evaluation of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-grafted liposomes for cancer thermochemotherapy. Int J Pharm. 2018;550(1-2):190–9. https://doi.org/10.1016/j.ijpharm.2018.08.027.

    Article  CAS  PubMed  Google Scholar 

  103. Han HD, Jeon YW, Kwon HJ, Jeon HN, Byeon Y, Lee CO, Cho SH, Shin BC. Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma. Acta Biomater. 2015;24:279–85. https://doi.org/10.1016/j.actbio.2015.06.019.

    Article  CAS  PubMed  Google Scholar 

  104. Wang CJ, Li W, Hu BC. The anti-tumor effect of folate-targeted liposome microbubbles loaded with oridonin as ultrasound-triggered tumor-targeted therapeutic carrier system. J Drug Target. 2017;25(1):83–91. https://doi.org/10.1080/1061186x.2016.1200588.

    Article  CAS  PubMed  Google Scholar 

  105. Li H, Yang X, Zhou Z, Wang K, Li C, Qiao H, Oupicky D, Sun M. Near-infrared light-triggered drug release from a multiple lipid carrier complex using an all-in-one strategy. J Control Release. 2017;261:126–37. https://doi.org/10.1016/j.jconrel.2017.06.029.

    Article  CAS  PubMed  Google Scholar 

  106. Chi YY, Yin XL, Sun KX, Feng SS, Liu JH, Chen DQ, Guo C, Wu Z. Redox-sensitive and hyaluronic acid functionalized liposomes for cytoplasmic drug delivery to osteosarcoma in animal models. J Control Release. 2017;261:113–25. https://doi.org/10.1016/j.jconrel.2017.06.027.

    Article  CAS  PubMed  Google Scholar 

  107. Dwivedi P, Kiran S, Han SY, Dwivedi M, Khatik R, Fan R, Mangrio FA, du K, Zhu Z, Yang C, Huang F, Ejaz A, Han R, Si T, Xu RX. Magnetic targeting and ultrasound activation of liposome-microbubble conjugate for enhanced delivery of anticancer therapies. ACS Appl Mater Interfaces. 2020;12(21):23737–51. https://doi.org/10.1021/acsami.0c05308.

    Article  CAS  PubMed  Google Scholar 

  108. Li H, Li XM, Shi XL, Li Z, Sun YJ. Effects of magnetic dihydroartemisinin nano-liposome in inhibiting the proliferation of head and neck squamous cell carcinomas. Phytomedicine. 2019;56:215–28. https://doi.org/10.1016/j.phymed.2018.11.007.

    Article  CAS  PubMed  Google Scholar 

  109. Bernard AL, Guedeau-Boudeville MA, Marchi-Artzner V, Gulik-Krzywicki T, Jullien L. Shear-induced permeation and fusion of lipid vesicles. J Colloid Interface Ence. 2005;287(1):298–306. https://doi.org/10.1016/j.jcis.2004.12.019.

    Article  CAS  Google Scholar 

  110. Nel AE, Mdler L, Velegol D, Xia T, Thompson M. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009;8(7):543–57. https://doi.org/10.1038/nmat2442.

    Article  CAS  PubMed  Google Scholar 

  111. Chen ZJ, Yang SC, Liu XL, Gao YH, Dong X, Lai X, Zhu MH, Feng HY, Zhu XD, Lu Q, Zhao M, Chen HZ, Lovell JF, Fang C. Nanobowl-supported liposomes improve drug loading and delivery. Nano Lett. 2020;20(6):4177–87. https://doi.org/10.1021/acs.nanolett.0c00495.

    Article  CAS  PubMed  Google Scholar 

  112. Jensen GM, Hodgson DF. Opportunities and challenges in commercial pharmaceutical liposome applications. Adv Drug Deliv Rev. 2020;154:2–12. https://doi.org/10.1016/j.addr.2020.07.016.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No.22078234).

Author information

Authors and Affiliations

  1. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Jia Wang, Junbo Gong & Zhenping Wei

Authors
  1. Jia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junbo Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenping Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception: Jia Wang and Zhenping Wei. Design of the work: Jia Wang. Writing—review and editing: Jia Wang. Supervision: Zhenping Wei and Junbo Gong. Project administration: Zhenping Wei. Funding acquisition: Junbo Gong. All authors contributed to the final version of the manuscript.

Corresponding author

Correspondence to Zhenping Wei.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Gong, J. & Wei, Z. Strategies for Liposome Drug Delivery Systems to Improve Tumor Treatment Efficacy. AAPS PharmSciTech 23, 27 (2022). https://doi.org/10.1208/s12249-021-02179-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-021-02179-4

KEY WORDS

Search

Navigation