Srilakshmi Muthyala

Background: Breast cancer is the second-highest cause of female deaths, and triple-negative breast cancer (TNBC) lacks many drug target receptors, such as estrogen, increasing treatment difficulty.^1,2 Recent studies show the potential for nanosomal lipid carrier structures in enhancing treatment. Two main types of these carriers, solid lipid nanocarriers (SLNs) and nanostructured lipid carriers (NLCs), have been used to deliver treatments. SLNs are a part of the first generation of nanosomal lipid carriers and consist of a core of solid lipids, whereas NLCs are in the second generation, containing both solid and liquid lipids. Combining these carriers with short chains of amino acid, cell-penetrating peptides (CPPs), has shown potential for specific cell targeting in drug delivery.³ There have, however, been discrepancies in whether NLCs or SLNs are superior in drug delivery.

Objectives: This review focused on understanding the role of both types of nanosomal lipid carriers, NLCs and SLNs, ligated with different types of CPPs in cell-specific targeting in triple-negative breast cancer models.

Search Methods: A literature search was conducted using PubMed, Google Scholar, and Perplexity AI using keywords such as “cell penetrating peptides and drug delivery”, “triple negative breast cancer”, and “nanosomal lipid carriers in breast cancer treatment.” The timeframe was limited to 2019-2026.

Results: The data from the literature search showed significant benefits from combining CPPs with nanosomal carriers in targeting tumors. A study conducted on a triple-negative breast cancer mouse model demonstrated a significant decrease in tumor size and enhanced tumor site-specific targeting using NLCs ligated with polyarginine-based CPPs to deliver two chemotherapeutics, paclitaxel and gambogic acid.³ A follow-up study underscored the benefit of using organelle-specific CPPs in inhibiting pulmonary metastasis.⁴ SLNs ligated with another CPP, c-peptides stemming from the endostatin protein, were also found to reduce the number of pulmonary metastatic nodules in a breast cancer mouse model.⁵ Utilizing CPP-attached NLCs to deliver chemotherapeutics also demonstrated hepatoprotective benefits with a reduction in levels of AST and ALT when compared to administering the drugs as a solution.³ To determine whether SLNs or NLCs were more effective as carriers, a study characterized their physical properties. It found that SLNs had a more stable structure and constant zeta potential, indicating more colloidal stability. SLNs also had a higher entrapment efficiency, the amount of drug taken up by the particle over the amount given.⁶ A human trial in breast cancer patients found that using nanosomal lipid suspensions to deliver paclitaxel improved response rates compared with delivering the drug traditionally, with ethanol and polyethoxylated castor oil.⁷

Conclusion: Utilizing CPPs attached to nanosomal lipid carrier structures to deliver chemotherapeutics has an inhibitory effect on tumor growth and metastasis while also reducing off-target effects. Although preliminary studies using these carriers have shown promising results in human patients, CPPs ligated with carriers have not yet been studied in humans. Future research on this topic with human trials can open up new ways of delivering chemotherapeutics and targeting aggressive tumors.

Works Cited:

1. Wen X, Guo X, Wang S, Lu Z, Zhang Y. Breast cancer diagnosis: A systematic review. Biocybernetics and Biomedical Engineering. 2024/01/01/ 2024;44(1):119-148. doi:https://doi.org/10.1016/j.bbe.2024.01.002
2. Rahdari T, Mahdavimehr M, Ghafouri H, Ramezanpour S, Ehtesham S, Asghari SM. Advancing triple-negative breast cancer treatment through peptide decorated solid lipid nanoparticles for paclitaxel delivery. Sci Rep. 2025;15(1):6043. Published 2025 Feb 19. doi:10.1038/s41598-025-90107-y
3. Ma Z, Li N, Zhang B, et al. Dual drug-loaded nano-platform for targeted cancer therapy: toward clinical therapeutic efficacy of multifunctionality. J Nanobiotechnology. 2020;18(1):123. Published 2020 Sep 4. doi:10.1186/s12951-020-00681-8
4. Dang W, Xing B, Jia X, et al. Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer. Int J Nanomedicine. 2023;18:3047-3068. Published 2023 Jun 8. doi:10.2147/IJN.S413680
5. Rahdari T, Mahdavimehr M, Ghafouri H, Ramezanpour S, Ehtesham S, Asghari SM. Advancing triple-negative breast cancer treatment through peptide decorated solid lipid nanoparticles for paclitaxel delivery. Sci Rep. 2025;15(1):6043. Published 2025 Feb 19. doi:10.1038/s41598-025-90107-y
6. Peira E, Sapino S, Chirio D, et al. Formulation and Comparative Characterization of SLNs and NLCs for Targeted Co-Delivery of Paclitaxel and Hydroxytyrosol Carboxylic Acid Esters Against Triple-Negative Breast Cancer. Pharmaceutics. 2025;17(9):1208. Published 2025 Sep 16. doi:10.3390/pharmaceutics17091208
7. Satheesh CT, Taran R, Singh JK, et al. Treatment with nanosomal paclitaxel lipid suspension versus conventional paclitaxel in metastatic breast cancer patients – a multicenter, randomized, comparative, phase II/III clinical study. Ther Adv Med Oncol. 2024;16:17588359241236442. Published 2024 Apr 25. doi:10.1177/17588359241236442