Cell Membrane-Inspired Polymeric Vesicles for Combined Photothermal and Photodynamic Prostate Cancer Therapy

Abstract

Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as highly prospective therapeutic modalities in cancer therapy. Notwithstanding, a critical challenge still remains in the exploration of an effective strategy to maximize the synergistic efficacy of PTT and PDT due to low photoconversion efficiency. Herein, inspired by the phospholipid bimolecular structure of the cell membrane, bionic cell membrane polymeric vesicles with photothermal/photodynamic synergy for prostate cancer therapy at one wavelength's excitation are constructed in one step by the coordination of hexadecyl trimethyl ammonium bromide (CTAB) from the surface of hydrophobic gold nanorods (AuNRs) with indocyanine green (ICG) and polycaprolactone (PCL), achieving their self-assembly in aqueous solutions. Importantly, the aggregation of the assembly improves the stability of the vesicles, realizing the synergistic effect of PTT and PDT for prostate cancer therapy. After being assembled within polymeric vesicles, bifunctional photosensitizer ICG can generate reactive oxygen species (ROS) and photothermal effect under light treatment. Their ROS not only induce PDT efficacy but also destroy the integrity of the lysosomal membrane, promoting the translocation of ICG and another photosensitizer called gold nanorods (AuNRs) into the cytosol. Moreover, their photothermal effects produced by both photosensitizers are able to engender greater damage to the tumor cells because of the close distance with organelles. This structure manifests good cellular uptake, highly effective tumor accumulation, high photothermal conversion efficiency, and excellent properties of enhanced photobleaching resistance, which are beneficial to ICG-based fluorescence tumor imaging. Using the same near-infrared (NIR) wavelength for excitation, the AuNR/ICG vesicles can reduce the side effect rate of photodamage on the skin. In addition, by generating reactive oxygen species (ROS) and double photothermal effect, the vesicles under NIR excitation can promote the apoptosis of PC3 tumor cells. Taken together, the spontaneous self-assembled AuNR/ICG vesicles exhibit huge potential in advanced-stage prostate cancer therapy, especially for the prostate-specific membrane antigen (PSMA)-negative castration-resistant subtype.

Keywords: cell membrane inspired; photodynamic therapy; photothermal therapy; prostate cancer; vesicles.