Enhanced Antitumor Efficacy and Imaging Application of Photosensitizer-Formulated Paclitaxel
journal contributionposted on 17.01.2020, 17:09 by Linlin Li, Dan Chen, Ke Zheng, Libin Jiang, Tao Dai, Ling Yang, Longguang Jiang, Zhuo Chen, Cai Yuan, Mingdong Huang
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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light illuminationcombination therapylysosome colocalization680 nm light irradiationcell cycle arresttumor regressionphotosensitizer nanoparticlesapoptotic responsetumor sitePPNTmicrotubule disassemblytumor eliminationPDTEnhanced Antitumor Efficacytumor ablation effectmouse modelPhotosensitizer-Formulated Paclitaxel Paclitaxelfluorescence tomographic imaginganticancer drugantitumor efficacyImaging Applicationphotodynamic therapyPTX safetytumor-bearing mouse modelamphipathic photosensitizerPNT