Water-soluble, Zwitterionic Poly-photosensitizers as Carrier-free, Photosensitizer-Self-Delivery System for in Vivo Photodynamic Therapy
ACS applied materials & interfaces | 8 Nov 2019
N Zheng, D Xie, C Wang, Z Zhang, Y Zheng, Q Lu, Y Bai, Y Li, A Wang and W Song
Polymeric nanoparticles (NPs) have been widely established to deliver most of the hydrophobic chemo-drugs or photosensitizers (PSs) for cancer therapy. However, this strategy is usually hindered by the relatively low drug loading capacity and the undesired toxicity as well as the immunogenicity caused by the non-therapeutic, polymeric carriers. The carrier-free, drug self-delivery systems, in which the chemo-drugs or their prodrugs themselves formed the NPs without the addition of non-therapeutic carriers, have been extensively developed to achieve high drug loading capacity and low systemic toxicity. However, most of the driving forces to form the NPs were based on the strong hydrophobic interactions, which were the undesired forces for the porphyrin-based hydrophobic PSs due to the parasitic aggregation caused quenching (ACQ) effect. Herein, the zwitterionic, water-soluble and ROS cleavable poly-photosensitizers (pPS) were prepared by the polymerization method, which spontaneous introduced different charges associated with the “desired electrostatic effect” and reduced the “undesired aggregation” by separating the PS monomers using flexible and ROS cleavable linkers. The obtained pPS could self-assembled into the nano-complexes based on the electrostatic effect with high PS loading capacity, improved singlet oxygen generation ability and efficient photo-toxicity. Upon PEG or HA coating on the surface, both pPS/PEG and pPS/HA complexes exhibited enhanced stability under physiological environments and excellent in vivo anti-tumor efficacy. Moreover, HA coated complexes also exhibited active tumor targeting. Such polymerization strategy comprehensively addressed the parasitic issues for the hydrophobic PSs self-delivery system in PDT area.
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