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A tumor microenvironment-activatable nanoplatform with phycocyanin-assisted in-situ nanoagent generation for synergistic treatment of colorectal cancer.
Sun, Xiaoxiao; Liang, Xiaoye; Wang, YuKai; Ma, Pengcheng; Xiong, Weiwei; Qian, Shiyu; Cui, Yu; Zhang, Haiyang; Chen, Xiang; Tian, Fang; Shi, Yang; Zheng, Fenfen; Li, Lingling.
Afiliación
  • Sun X; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Liang X; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Wang Y; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Ma P; School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, China.
  • Xiong W; School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, China.
  • Qian S; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Cui Y; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Zhang H; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Chen X; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Tian F; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Shi Y; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
  • Zheng F; School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, China. Electronic address: zhengfenfen@just.edu.cn.
  • Li L; Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. Electronic address: lill@njmu.edu.cn.
Biomaterials ; 301: 122263, 2023 10.
Article en En | MEDLINE | ID: mdl-37549506
The in-situ generation of therapeutic agents in targeted lesions is promising for revolutionizing oncotherapy but is limited by the low production efficiency. Given the specific tumor microenvironment (TME) of colorectal cancer (CRC), i.e., mild acidity, overexpressed H2O2, glutathione (GSH) and H2S, we develop phycocyanin (PC) encapsulated PZTC/SS/HA nanocapsules (NCs) for TME-responsive, protein-assisted "turn-on'' therapy of CRC. The NCs are prepared by sequentially assembling Cu2+-tannic acid (TA) coordination shell, disulfide bond-bearing cross-linker, and hyaluronic acid (HA) on the sacrificial template ZIF-8, thus achieving pH-, GSH-responsiveness, and tumor targeting capability, respectively. Once reaching the CRC sites, the NCs can quickly disintegrate and release Cu2+ and PC, accompanied by subsequent endogenous H2S-triggered generation of copper sulfide (CuS). Significantly, the intracellular sulfidation process can be accelerated by PC, thereby enabling efficient photothermal therapy (PTT) under NIR-Ⅱ laser. Besides, Cu2+-associated chemodynamic therapy (CDT) can be simultaneously activated and enhanced by PTT-induced local hyperthermia and disulfide bond-induced GSH consumption. This CRC-targeted and TME-activated synergistic PTT/CDT strategy displays high therapeutic efficacy both in vitro and in vivo, which can open up a new avenue for biomolecule-assisted in-situ nanoagent generation and effective TME-responsive synergistic treatment of CRC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Nanocápsulas / Nanopartículas / Neoplasias Límite: Humans Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Nanocápsulas / Nanopartículas / Neoplasias Límite: Humans Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos