Coassembled Nanoparticles Constructed from Trisulfide\nBond-Modified Docetaxel and Hematoporphyrin for Treating 4T1 Breast\nTumors

Docetaxel (DTX) injection, a first-line\nchemotherapy treatment\nfor breast cancer, encounters clinical constraints owing to its systemic\nside effects. To address these issues, we innovatively prepared nanoparticles\n(NPs) by coassembling a trisulfide bond-modified DTX (DSSSD) with\nhematoporphyrin (HP), a photosensitizer. This resulted in DSSSD/HP\nNPs exhibiting a spherical morphology and a uniform size distribution.\nFor comparison, a control group of DSSD/HP NPs was also formulated,\nusing a disulfide bond-modified DTX (DSSD) instead of DSSSD. The results\nof the <i>in vitro</i> drug release study revealed that\nDSSSD/HP NPs exhibited a higher redox-responsive release capability\ncompared with DSSD/HP NPs. Furthermore, when exposed to near-infrared\nirradiation, DSSSD/HP NPs exhibited increased cytotoxicity by generating\nabundant reactive oxygen species, inducing greater glutathione depletion,\nand upregulating the apoptotic Bax protein expression, all of which\nsurpassed the effects observed with DSSD/HP NPs. DSSSD/HP NPs improved\nthe pharmacokinetic behaviors of DTX in rats, enhancing its distribution\nand accumulation within tumor tissues, while mitigating adverse effects\nin 4T1 breast tumor-bearing mice. This integration of DTX-mediated\nchemotherapy with HP-triggered photodynamic therapy resulted in a\nnotable improvement in antitumor efficacy. Therefore, the ideas and\nfindings of DSSSD/HP NPs presented in this study provide a strategy\nfor combining of trisulfide bond-modified drugs with photodynamic\ntherapy.