A pH-Sensitive Self-Assembled and Carrier-Free Nanoparticle Based on Charge Reversal for Enhanced Synergetic Chemo-Phototherapy.

To overcome biological barriers for nanoparticles (NPs) efficaciously accumulated at tumor sites, as well as enhancing the performance of drug delivery systems, a carrier-free nanoparticle based on charge reversal is designed for improved synergetic chemo-phototherapy for cancer treatment. In this system, doxorubicin (Dox) and zinc phthalocyanine (ZnPc) are self-assembled through noncovalent interactions (π-π stacking, hydrophobic forces) to avoid the possible toxicity of excipient, complex chemical conjugations and batch-to-batch variation. A trace amount of poly(2-(di-methylamino) ethylmethacrylate)- poly[(R)-3-hydroxybutyrate]- poly(2-(dimethylamino) ethylmethacrylate (PDMAEMA-PHB-PDMAEMA) is modified on the surface of Dox-ZnPc to construct the novel nanoparticles, namely DZP, with long-term stability, and with a dual-drug load content of up to ≈90％. The drug delivery system (DDS) can effectively decrease its toxicity among physical circulation and increase the accumulation at the tumor site. Moreover, the developed DZP nanoparticles show excellent photo-chemotherapy, photoacoustic (PA) and fluorescence (FL) imaging characteristics for multimodal imaging-guided synergetic therapy.