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5 years ago

Photosensitive Nanoparticles Combining Vascular-Independent Intratumor Distribution and On-Demand Oxygen-Depot Delivery for Enhanced Cancer Photodynamic Therapy

Photosensitive Nanoparticles Combining Vascular-Independent Intratumor Distribution and On-Demand Oxygen-Depot Delivery for Enhanced Cancer Photodynamic Therapy
Leihou Shao, Xuan Wang, Yujia Tong, Caiyan Zhao, Xiongwei Deng, Long Chen, Yan Wu, Xianlei Li, Jianqing Lu
In drug delivery, the poor tumor perfusion results in disappointing therapeutic efficacy. Nanomedicines for photodynamic therapy (PDT) greatly need deep tumor penetration due to short lifespan and weak diffusion of the cytotoxic reactive oxygen species (ROS). The damage of only shallow cells can easily cause invasiveness and metastasis. Moreover, even if the nanomedicines enter into deeper lesion, the effectiveness of PDT is limited due to the hypoxic microenvironment. Here, a deep penetrating and oxygen self-sufficient PDT nanoparticle is developed for balanced ROS distribution within tumor and efficient cancer therapy. The designed nanoparticles (CNPs/IP) are doubly emulsified (W/O/W) from poly(ethylene glycol)-poly(ε-caprolactone) copolymers doped with photosensitizer IR780 in the O layer and oxygen depot perfluorooctyl bromide (PFOB) inside the core, and functionalized with the tumor penetrating peptide Cys-Arg-Gly-Asp-Lys (CRGDK). The CRGDK modification significantly improves penetration depth of CNPs/IP and makes the CNPs/IP arrive at both the periphery and hypoxic interior of tumors where the PFOB releases oxygen, effectively alleviating hypoxia and guaranteeing efficient PDT performance. The improved intratumoral distribution of photosensitizer and adequate oxygen supply augment the sensitivity of tumor cells to PDT and significantly improve PDT efficiency. Such a nanosystem provides a potential platform for improved therapeutic index in anticancer therapy. A deep tumor-penetrating nanoparticle is developed for O2 self-sufficient photodynamic therapy (PDT) agent delivery to achieve optimal PDT therapeutic effect, which could deeply penetrate into the hypoxic interior of tumor and homogeneously distribute among all relevant tumor compartments after systemic administration. In hypoxic microenvironment, the perfluorooctyl bromide in nanoparticles releases O2, effectively alleviating the hypoxia and guaranteeing the efficient PDT performance.

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

DOI: 10.1002/smll.201703045

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