Transferrin-modified multicomponent liposomes encapsulating paclitaxel-loaded -elemene microemulsion enhance therapeutic efficacy in non-small-cell lung cancer.

To achieve efficient accumulation and facilitate profound penetration of anti-tumor agents within neoplastic tissues stands as one of the most critical determinants influencing the efficacy of anticancer therapies. Herein, a multicomponent-based liposomes (Tf-PEM/L) by transferrin-modified encapsulating paclitaxel (PTX)-loaded -elemene microemulsion (PEM) was fabricated, demonstrating significantly enhanced therapeutic efficacy against non-small cell lung cancer (NSCLC). Leveraging the synergistic mechanism of transferrin-mediated active targeting coupled with the enhanced permeability and retention (EPR) effect, Tf-PEM/L demonstrates a pronounced propensity for efficient and substantial accumulation at the tumor site. Following accumulation, the subsequently released PEM enables highly efficient deep penetration within tumor tissue, thereby achieving favorable anti-tumor therapeutic efficacy. Characterization of Tf-PEM/L revealed a mean particle size approximately (144.76 ± 9.34) nm, while the zeta potential exhibited a measurement of (-12.52 ± 0.28) mV. Notably, the transmission electron microscopy (TEM) images revealed the small-sized PEM were encapsulated within large-sized liposomes. In vitro cytotoxicity assays demonstrated that Tf-PEM/L elicited synergistic antitumor effects against A549 cells, underscoring its combinatorial therapeutic potential. In vivo studies, Tf-PEM/L demonstrated exceptional tumor-targeting capabilities as evidenced by quantitative biodistribution analyses. Moreover, Tf-PEM/L exhibited superior antitumor efficacy with tumor inhibition rate of (81.36 ± 3.87)% while markedly attenuating systemic toxicity, positioning it as a promising therapeutic strategy for NSCLC. Collectively, the Tf-PEM/L represents a promising targeted therapeutic strategy for NSCLC, with enhanced efficacy and safety profiles.