Coassembled Nanoparticles Constructed from Trisulfide Bond-Modified Docetaxel and Hematoporphyrin for Treating 4T1 Breast Tumors

Abstract

Docetaxel (DTX) injection, a first-line chemotherapy treatment for breast cancer, encounters clinical constraints owing to its systemic side effects. To address these issues, we innovatively prepared nanoparticles (NPs) by coassembling a trisulfide bond-modified DTX (DSSSD) with hematoporphyrin (HP), a photosensitizer. This resulted in DSSSD/HP NPs exhibiting a spherical morphology and a uniform size distribution. For comparison, a control group of DSSD/HP NPs was also formulated, using a disulfide bond-modified DTX (DSSD) instead of DSSSD. The results of the in vitro drug release study revealed that DSSSD/HP NPs exhibited a higher redox-responsive release capability compared with DSSD/HP NPs. Furthermore, when exposed to near-infrared irradiation, DSSSD/HP NPs exhibited increased cytotoxicity by generating abundant reactive oxygen species, inducing greater glutathione depletion, and upregulating the apoptotic Bax protein expression, all of which surpassed the effects observed with DSSD/HP NPs. DSSSD/HP NPs improved the pharmacokinetic behaviors of DTX in rats, enhancing its distribution and accumulation within tumor tissues, while mitigating adverse effects in 4T1 breast tumor-bearing mice. This integration of DTX-mediated chemotherapy with HP-triggered photodynamic therapy resulted in a notable improvement in antitumor efficacy. Therefore, the ideas and findings of DSSSD/HP NPs presented in this study provide a strategy for combining of trisulfide bond-modified drugs with photodynamic therapy.