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Water-Soluble, Zwitterionic Poly-photosensitizers as Carrier-Free, Photosensitizer-Self-Delivery System for in Vivo Photodynamic Therapy

Author:
Zheng, Nan, Xie, Dan, Wang, Chunsen, Zhang, Zhiyi, Zheng, Yubin, Lu, Qing, Bai, Yugang, Li, Yang, Wang, Aiguo, Song, Wangze
Source:
ACS applied materials & interfaces 2019 v.11 no.47 pp. 44007-44017
ISSN:
1944-8252
Subject:
cancer therapy, coatings, hyaluronic acid, hydrophobic bonding, hydrophobicity, immunogenicity, nanoparticles, neoplasms, photochemotherapy, photosensitizing agents, phototoxicity, polyethylene glycol, polymerization, singlet oxygen, water solubility, zwitterions
Abstract:
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 nontherapeutic, 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 nontherapeutic carriers, have been extensively developed to achieve a 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 effect. Herein, the zwitterionic, water-soluble, and reactive oxygen species (ROS)-cleavable poly-photosensitizers (pPSs) were prepared by the polymerization method, which spontaneously 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 be self-assembled into the nanocomplexes based on the electrostatic effect with a high PS loading capacity, improved singlet oxygen generation ability, and efficient phototoxicity. Upon poly(ethylene glycol) (PEG) or hyaluronic acid (HA) coating on the surface, both pPS/PEG and pPS/HA complexes exhibited enhanced stability under physiological environments and excellent in vivo antitumor efficacy. Moreover, HA-coated complexes also exhibited active tumor targeting. Such a polymerization strategy comprehensively addressed the parasitic issues for the hydrophobic PS self-delivery system in the photodynamic therapy area.
Agid:
6774241