4 years ago

Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near-Infrared Photosensitized Nanoparticles

Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near-Infrared Photosensitized Nanoparticles
Zhanjun Li, Gang Han, Yuanwei Zhang, Yucheng Yang, Jinyi Yang, Aarushi Iris Pendharkar, Ling Huang, Jianzhang Zhao, Sharon Kelmar, Liyong Chen, Yang Zhao, Wenting Wu
Photodynamic therapy (PDT) is an important cancer treatment modality due to its minimally invasive nature. However, the efficiency of existing PDT drug molecules in the deep-tissue-penetrable near-infrared (NIR) region has been the major hurdle that has hindered further development and clinical usage of PDT. Thus, herein a strategy is presented to utilize a resonance energy transfer (RET) mechanism to construct a novel dyad photosensitizer which is able to dramatically boost NIR photon utility and enhance singlet oxygen generation. In this work, the energy donor moiety (distyryl-BODIPY) is connected to a photosensitizer (i.e., diiodo-distyryl-BODIPY) to form a dyad molecule (RET-BDP). The resulting RET-BDP shows significantly enhanced absorption and singlet oxygen efficiency relative to that of the acceptor moiety of the photosensitizer alone in the NIR range. After being encapsulated with biodegradable copolymer pluronic F-127-folic acid (F-127-FA), RET-BDP molecules can form uniform and small organic nanoparticles that are water soluble and tumor targetable. Used in conjunction with an exceptionally low-power NIR LED light irradiation (10 mW cm−2), these nanoparticles show superior tumor-targeted therapeutic PDT effects against cancer cells both in vitro and in vivo relative to unmodified photosensitizers. This study offers a new method to expand the options for designing NIR-absorbing photosensitizers for future clinical cancer treatments. Resonance energy transfer constructed NIR-absorbing BODIPY-based photosensitized dyad nanoparticles are developed. These nanoparticles enable targeted photodynamic therapy upon application of low-power NIR LED light irradiation. This work provides a new concept for the design of biocompatible nanoparticles with significantly improved NIR sensitivity, which is key to photodynamic therapy development.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adma.201604789

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