间充质干细胞膜包被的负载 TPCS(2a) 纳米颗粒用于乳腺癌光动力治疗

Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects.

However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues.

Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS 2a ). TPCS 2a @NPs of 98. 89 18. 56 nm with an encapsulation efficiency percentage (EE%) of 81. 9 7. 92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS 2a @NPs, size of 139. 31 12. 94 nm).

The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS 2a @NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS 2a @NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells.

Moreover, encapsulation of TPCS 2a in mMSC-TPCS 2a @NPs effectively prevents its aggregation, ensuring efficient singlet oxygen ( 1 O 2 ) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC 50 < 0. 15 M) and three-dimensional spheroids.