光敏剂
光动力疗法
紫杉醇
体内
生物物理学
材料科学
癌症研究
化学
生物
化疗
光化学
有机化学
遗传学
生物技术
作者
Linlin Li,Dan Chen,Ke Zheng,Ling Jiang,Tao Dai,Ling Yang,Longguang Jiang,Zhuo Chen,Cai Yuan,Mingdong Huang
标识
DOI:10.1021/acsami.9b18396
摘要
Paclitaxel (PTX) is a widely used anticancer drug that works by inhibiting microtubule disassembly. PTX safety was greatly enhanced by embedding it with human albumin. Here, we study the synergistic effects of PTX with photodynamic therapy (PDT) both in vitro and in vivo by constructing photosensitizer–PTX nanotheranostics (PPNTs). PPNTs were fabricated via noncovalent hydrophobic interactions and π–π stacking between an amphipathic photosensitizer and PTX with an average diameter of ∼80 nm, and these showed high stability in biological conditions. In a tumor-bearing mouse model, PPNTs were shown to accumulate at the tumor site based on three-dimensional fluorescence tomographic imaging. Under 680 nm light irradiation, PPNTs exhibited a superior solid tumor ablation effect in a mouse model, with a dose of PTX (0.2 mg/kg) that is 10-fold lower than that typically used. Mechanistically, PPNTs induced a strong apoptotic response in cells under light illumination and showed an increased antitumor efficacy that is 47.2-fold and 57.6-fold higher than that of the photosensitizer nanoparticles (PNTs) and free PTX, respectively. In addition, PPNTs showed enhanced cellular uptake with focused mitochondria and lysosome colocalization compared to that of PNTs and the amount of PTX delivered in PPNTs was sufficient to induce cell cycle arrest in the G2/M phase. These findings indicated that the current combination therapy has advantages over monotherapy in promoting tumor regression and ultimately achieving tumor elimination.
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