808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd³⁺-sensitized upconversion emission with enhanced anti-tumor efficacy

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• 作者：Zhiyao Hou^a ; Kerong Deng^a ; ^c ; Chunxia Li^a ; ^{cxli@ciac.ac.cn" class="auth_mail" title="E-mail the corresponding author} ; Xiaoran Deng^a ; ^c ; Hongzhou Lian^a ; Ziyong Cheng^a ; Dayong Jin^b ; Jun Lin^a ; ^{jlin@ciac.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Photodynamic therapy ; 808 nm light ; Hyaluronic acid target ; Nd3+-sensitized upconversion nanoparticles ; Dual-photosensitizers nanoplatform
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：32-46
• 全文大小：4741 K

文摘

The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYFb>4b>:Yb/Tm@NaYFb>4b>:Yb@NaNdFb>4b>:Yb@NaYFb>4b> (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiOb>2b>, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiOb>2b> shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd³⁺-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.