The Role of Liposomal Delivery Systems in the Treatment of Triple Negative Breast Cancer

Abstract

This study aims to highlight the potential of liposomal nanocarrier systems in addressing the challenges associated with the treatment of triple-negative breast cancer (TNBC) and to provide a literature-based foundation for their use in targeted therapeutic approaches. This study evaluating the efficacy of liposomal drug delivery systems in TNBC treatment, along with current developments reported in the literature. Particular emphasis is placed on surface modifications involving PEGylation, antibodies, aptamers, and small molecules, and their impact on therapeutic success. TNBC accounts for approximately 20% of all breast cancer cases and represents a highly aggressive subtype characterized by treatment resistance and high metastatic potential. Conventional treatment methods often fall short, with recurrence observed in about 40% of cases and mortality reaching 80–90% due to therapy-resistant tumors. Liposomes have garnered attention due to their ability to enhance drug bioavailability, reduce systemic toxicity, and provide tumor site-specific targeting. Numerous formulations have been developed, ranging from PEGylated liposomes to antibody- and aptamer-conjugated systems, demonstrating therapeutic efficacy in various TNBC cell lines and animal models. Given the aggressive nature of TNBC and the limited treatment options, liposomal nanocarrier systems offer a promising alternative. The integration of these systems with specific targeting modifications may lay the groundwork for future personalized and more effective TNBC therapies. To facilitate clinical translation, it is essential to establish standardized production protocols, streamline regulatory processes, and strengthen interdisciplinary collaborations.

Keywords

• Triple-Negative Breast Cancer
• Liposome
• Targeted Therapy
• Drug Delivery Systems
• Nanotechnology

References

1. Kim J, Harper A, McCormack V, et al. Global patterns and trends in breast cancer incidence and mortality across 185 countries. Nat Med. 2025. doi:10.1038/s41591-025-03502-3
2. Tarantino P, Corti C, Schmid P, et al. Immunotherapy for early triple negative breast cancer: research agenda for the next decade. NPJ Breast Cancer. 2022;8(23). doi:10.1038/s41523-022-00386-1
3. Kumar H, Gupta NV, Jain R, et al. A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer. J Adv Res. 2023;54:271–292. doi:10.1016/j.jare.2023.02.005
4. Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer: expanded options, evolving needs. Nat Rev Clin Oncol. 2022;19:91–113. doi:10.1038/s41571-021-00565-2
5. Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer. 2022;8(95). doi:10.1038/s41523-022-00468-0
6. Liu J, Xiao Q, Xiao J, et al. Wnt/β-catenin signalling: Function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther. 2022;7(3). doi:10.1038/s41392-021-00762-6
7. Liao M, Zhang J, Wang G, et al. Small-molecule drug discovery in triple negative breast cancer: Current situation and future directions. J Med Chem. 2021;64:2382–2418. doi:10.1021/acs.jmedchem.0c01180
8. Fidan Y, Stela M, Selin Seda T, Gürsoy RN. Recent advances in liposome-based targeted cancer therapy. J Liposome Res. 2024;34:316–334. doi:10.1080/08982104.2023.2268710

9. Morales-Cruz M, Delgado Y, Castillo B, et al. Smart targeting to improve cancer therapeutics. Drug Des Devel Ther. 2019;13:3753–3772. doi:10.2147/DDDT.S219489
10. da Silva JL, Cardoso Nunes NC, Izetti P, et al. Triple negative breast cancer: A thorough review of biomarkers. Crit Rev Oncol Hematol. 2020;145:102855. doi:10.1016/j.critrevonc.2019.102855
11. Coussy F, Lavigne M, de Koning L, et al. Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts. Theranostics. 2020;10:1531–1543. doi:10.7150/thno.36182
12. Linares RL, Benítez JGS, Reynoso MO, et al. Modulation of the leptin receptors expression in breast cancer cell lines exposed to leptin and tamoxifen. Sci Rep. 2019;9:19189. doi:10.1038/s41598-019-55674-x
13. Chen X, Feng L, Huang Y, et al. Mechanisms and strategies to overcome PD-1/PD-L1 blockade resistance in triple-negative breast cancer. Cancers (Basel). 2022;15. doi:10.3390/cancers15010104
14. Zhai B, Chen P, Wang W, et al. An ATF(24) peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment. Cancer Biol Med. 2020;17:676–692. doi:10.20892/j.issn.2095-3941.2020.0454
15. Guo RC, Zhang XH, Ji L, et al. Recent progress of therapeutic peptide-based nanomaterials: From synthesis and self-assembly to cancer treatment. Biomater Sci. 2020;8:6175–6189. doi:10.1039/D0BM01358G
16. Zhu Y, Meng Y, Zhao Y, et al. Toxicological exploration of peptide-based cationic liposomes in siRNA delivery. Colloids Surf B Biointerfaces. 2019;179:66–76. doi:10.1016/j.colsurfb.2019.03.052
17. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer. 2002;2:750–763. doi:10.1038/nrc903
18. Buyuk B, Jin S, Ye K. Epithelial-to-mesenchymal transition signaling pathways responsible for breast cancer metastasis. Cell Mol Bioeng. 2022;15:1–13. doi:10.1007/s12195-021-00694-9
19. Liu D, Guo P, McCarthy C, et al. Peptide density targets and impedes triple-negative breast cancer metastasis. Nat Commun. 2018;9:2612. doi:10.1038/s41467-018-05035-5
20. Large DE, Abdelmessih RG, Fink EA, Auguste DT. Liposome composition in drug delivery design, synthesis, characterization, and clinical application. Adv Drug DelivRev. 2021;176:113851. doi:10.1016/j.addr.2021.113851
21. Medina MA, Oza G, Sharma A, et al. Triple-negative breast cancer: A review of conventional and advanced therapeutic strategies. Int J Environ Res Public Health. 2020;17. doi:10.3390/ijerph17062078
22. Danaei M, Dehghankhold M, Ataei S, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10. doi:10.3390/pharmaceutics10020057
23. Izadiyan Z, Misran M, Kalantari K, et al. Advancements in liposomal nanomedicines: Innovative formulations, therapeutic applications, and future directions in precision medicine. Int J Nanomedicine. 2025;20:1213–1262. doi:10.2147/IJN.S488961
24. Guimarães D, Cavaco-Paulo A, Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm. 2021;601:120571. doi:10.1016/j.ijpharm.2021.120571
25. Sercombe L, Veerati T, Moheimani F, et al. Advances and challenges of liposome-assisted drug delivery. Front Pharmacol. 2015;6:286. doi:10.3389/fphar.2015.00286
26. Liu Y, Castro Bravo KM, Liu J. Targeted liposomal drug delivery: A nanoscience and biophysical perspective. Nanoscale Horizons. 2021;6:78–94. doi:10.1039/D0NH00605J
27. Yan W, Leung SS, To KK. Updates on the use of liposomes for active tumor targeting in cancer therapy. Nanomedicine (Lond). 2020;15:303–318. doi:10.2217/nnm-2019-0308
28. Eroğlu İ, İbrahim M. Liposome-ligand conjugates: A review on the current state of art. J Drug Target. 2020;28:225–244. doi:10.1080/1061186X.2019.1648479
29. Ren H, He Y, Liang J, et al. Role of liposome size, surface charge, and PEGylation on rheumatoid arthritis targeting therapy. ACS Appl Mater Interfaces. 2019;11:20304–20315. doi:10.1021/acsami.8b22693
30. Zamani P, Teymouri M, Nikpoor AR, et al. Nanoliposomal vaccine containing long multi-epitope peptide E75-AE36 pulsed PADRE-induced effective immune response in mice TUBO model of breast cancer. Eur J Cancer. 2020;129:80–96. doi:10.1016/j.ejca.2020.01.010
31. Fatima M, Abourehab MAS, Aggarwal G, et al. Advancement of cell-penetrating peptides in combating triple-negative breast cancer. Drug Discov Today. 2022;27:103353. doi:10.1016/j.drudis.2022.103353
32. Lai WF, Wong WT, Rogach AL. Molecular design of layer-by-layer functionalized liposomes for oral drug delivery. ACS Appl Mater Interfaces. 2020;12:43341–43351. doi:10.1021/acsami.0c13504
33. Juan A, Cimas FJ, Bravo I, et al. An overview of antibody-conjugated polymeric nanoparticles for breast cancer therapy. Pharmaceutics. 2020;12. doi:10.3390/pharmaceutics12090802
34. Liao WS, Ho Y, Lin YW, et al. Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite. Acta Biomater. 2019;86:395–405. doi:10.1016/j.actbio.2019.01.025
35. Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22:61. doi:10.1186/s13058-020-01296-5
36. Brouckaert O, Wildiers H, Floris G, Neven P. Update on triple-negative breast cancer: Prognosis and management strategies. Int J Womens Health. 2012;4:511–520. doi:10.2147/IJWH.S18541
37. Guo P, Yang J, Liu D, et al. Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis. Sci Adv. 2019;5:eaav5010. doi:10.1126/sciadv.aav5010
38. Naik H, Sonju JJ, Singh S, et al. Lipidated peptidomimetic ligand-functionalized HER2 targeted liposome as nano-carrier designed for doxorubicin delivery in cancer therapy. Pharmaceuticals (Basel). 2021;14. doi:10.3390/ph14030221
39. Ghosh B, Biswas S. Polymeric micelles in cancer therapy: State of the art. J Control Release. 2021;332:127–147. doi:10.1016/j.jconrel.2021.02.016
40. Dong S, Bi Y, Sun X, et al. Dual-loaded liposomes tagged with hyaluronic acid have synergistic effects in triple-negative breast cancer. Small. 2022;18:e2107690.
41. Cadinoiu AN, Rata DM, Atanase LI, et al. Aptamer-functionalized liposomes as a potential treatment for basal cell carcinoma. Polymers (Basel). 2019;11.
42. Kim M, Lee JS, Kim W, et al. Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression. J Control Release. 2022;348:893–910. doi:10.1016/j.jconrel.2022.06.039
43. Zeng Y, Zhao L, Li K, et al. Aptamer-functionalized nanoplatforms overcoming temozolomide resistance in synergistic chemo/photothermal therapy through alleviating tumor hypoxia. Nano Res. 2023;16:9859–9872. doi:10.1007/s12274-023-5742-7
44. Sheikh A, Md S, Kesharwani P. Aptamer grafted nanoparticle as targeted therapeutic tool for the treatment of breast cancer. Biomed Pharmacother. 2022;146:112530.
45. Alshaer W, Hillaireau H, Vergnaud J, et al. Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model. J Control Release. 2018;271:98–106. doi:10.1016/j.jconrel.2017.12.022
46. Tang B, Peng Y, Yue Q, et al. Design, preparation and evaluation of different branched biotin modified liposomes for targeting breast cancer. Eur J Med Chem. 2020;193:112204. doi:10.1016/j.ejmech.2020.112204
47. Belfiore L, Saunders DN, Ranson M, Vine KL. N-Alkylisatin-loaded liposomes target the urokinase plasminogen activator system in breast cancer. Pharmaceutics. 2020;12. doi:10.3390/pharmaceutics12070641
48. Barbosa MV, Monteiro LOF, Carneiro G, et al. Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment. Colloids Surf B Biointerfaces. 2015;136:553–561. doi:10.1016/j.colsurfb.2015.09.055
49. Lin M, Teng L, Wang Y, et al. Curcumin-guided nanotherapy: A lipid-based nanomedicine for targeted drug delivery in breast cancer therapy. Drug Deliv. 2016;23:1420–1425.
50. Guo P, Yang J, Jia D, et al. ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent anti-angiogenic agents for triple negative breast cancer. Theranostics. 2016;6:1–13.