Enhanced antitumor efficacy and imaging application of photosensitizer-formulated Paclitaxel.

Paclitaxel (PTX) is widely used anti-cancer drug by inhibiting microtubule disassembly. PTX safety was greatly enhanced by embedding with human albumin. Here, we study the synergistic effects of PTX with photodynamic therapy (PDT) both in vitro and in vivo by forming photosensitizer-PTX nanotheranostics (PPNT). 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 high stability in biological conditions. In a tumor-bearing mouse model, PPNTs were shown to accumulate at the tumor based on the three-dimensional fluorescent tomographic imaging. Under 680 nm light irradiation, PPNTs achieved superior solid tumor ablation effect in a mouse model, with a dose of PTX (0.2 mg/kg) that is ten-fold lower than typically used. Mechanistically, PPNTs induced strong apoptotic response in cells upon light illumination, and showed increased antitumor efficacy at 47.2-fold and 57.6-fold higher than the photosensitizer nanoparticles (PNT) and free PTX respectively. In addition, PPNTs showed enhanced cellular uptake with focused mitochondria and lysosome co-localization compared to PNT, and the amount of PTX delivered in PPNTs was sufficient to induce cell cycle arrest in G2/M phase. These findings indicated that the current combination therapy have advantage over monotherapy in promoting tumor regression and ultimately achieving tumor elimination.