Synergizing Upconversion Nanophotosensitizers with Hyperbaric Oxygen to Remodel the Extracellular Matrix for Enhanced Photodynamic Cancer Therapy

Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosens...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2018-07, Vol.10 (27), p.22985-22996
Main Authors: Li, Jingqiu, Huang, Jinzhao, Ao, Yanxiao, Li, Shiyu, Miao, Yu, Yu, Zhongzheng, Zhu, Lingtao, Lan, Xiaoli, Zhu, Yanhong, Zhang, Yan, Yang, Xiangliang
Format: Article
Language:English
Subjects:
Animals
Extracellular Matrix - drug effects
Female
Hyperbaric Oxygenation
Mice
Mice, Inbred BALB C
Models, Biological
Nanoparticles - chemistry
Nanoparticles - toxicity
Photochemotherapy - methods
Photosensitizing Agents - pharmacology
Reactive Oxygen Species
Tumor Microenvironment - drug effects
Xenograft Model Antitumor Assays
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Summary:Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy. The UNPSs are designed to have an Nd3+-sensitized sandwiched structure, wherein the upconversion core serves as light transducers to transfer energy to the neighboring photosensitizers to produce reactive oxygen species (ROS). With HBO, photodynamic process can generate abundant ROS in the intrinsically hypoxic tumor. It is revealed for the first time that HBO-assisted PDT decomposes collagen in the extracellular matrix of tumor and thus facilitates the diffusion of oxygen and penetration of UNPSs into the deeper area of tumor. Such a synergic effect eventually results in a significantly enhanced therapeutic efficacy at a low laser power density as compared with that using UNPSs alone. In view of its good biosafety, the HBO-assisted and UNPSs-mediated PDT provides new possibilities for treatment of solid tumors.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b07090