Photodynamic therapy mediated by a selective nanoemulsion for breast cancer treatment: in vitro and in vivo evaluation

Abstract

In this study, we investigated the tumor-accumulating efficacy of photodynamic therapy (PDT) mediated by an aluminum chloride phthalocyanine-loaded nanoemulsion (AlClPc-NE) against breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-10A) cell lines. The optimized AlClPc-NE formulation exhibited a mean hydrodynamic diameter of 168 nm, zeta potential of − 29 mV, low polydispersity (0.25), encapsulation efficiency of 81.10%, and estimated stability of 12 months. The system effectively preserved the drug photoactivity, achieving a robust singlet oxygen quantum yield (ΦΔ = 0.52). In vitro assays confirmed excellent dark biocompatibility of the nanocomposites. Upon irradiation, AlClPc-PDT exhibited potent phototoxicity. Crucially, a selective therapeutic window was observed 24 h post-treatment at a light density of 1000 mJ/cm2, significantly reducing tumor cell viability by over 50% while preserving non-tumorigenic MCF-10A cells. This enhanced efficacy is attributed to the optimized cellular internalization and specific subcellular localization promoted by nanoemulsions. Translating these findings to an in vivo orthotopic breast cancer model, AlClPc-PDT significantly suppressed tumor progression, reducing the tumor mass by approximately 50%. Ultimately, the AlClPc-NE platform emerged as a highly localized therapeutic strategy, prioritizing tumor eradication while limiting the potential side effects in healthy tissues. A stable AlClPc-loaded nanoemulsion with high encapsulation efficiency and preserved photoactivity was successfully developed for photodynamic therapy applications. AlClPc-NE promoted enhanced cellular internalization and selective phototoxicity against breast cancer cells while preserving non-tumorigenic cells 24 h post-treatment. The nanoemulsion maintained the photosensitizer in an active monomeric state, achieving a high singlet oxygen quantum yield (ΦΔ = 0.52). In vivo photodynamic therapy mediated by AlClPc-NE significantly suppressed orthotopic breast tumor progression, reducing the tumor burden by approximately 50% under these conditions. A stable AlClPc-loaded nanoemulsion with high encapsulation efficiency and preserved photoactivity was successfully developed for photodynamic therapy applications. AlClPc-NE promoted enhanced cellular internalization and selective phototoxicity against breast cancer cells while preserving non-tumorigenic cells 24 h post-treatment. The nanoemulsion maintained the photosensitizer in an active monomeric state, achieving a high singlet oxygen quantum yield (ΦΔ = 0.52). In vivo photodynamic therapy mediated by AlClPc-NE significantly suppressed orthotopic breast tumor progression, reducing the tumor burden by approximately 50% under these conditions.