Affiliation:
1. School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences 1 Sub‐lane Xiangshan Hangzhou 310024 China
2. State Key Laboratory of High‐Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics Chinese Academy of Sciences 1295 Ding‐Xi Road Shanghai 200050 China
3. Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Beijing 100049 China
4. Nanotechnology and Intestinal Microecology Research Center Shanghai Tenth People's Hospital School of Medicine Tongji University 301 Yanchang Road Shanghai 200072 China
Abstract
AbstractThe characteristics of malignant solid tumors with dense extracellular matrix (ECM) and immunosuppressive microenvironment (IME) seriously restrict the high efficacy and precise treatment of tumors, leading to increased susceptibility to malignant recurrence and metastasis. Herein, an ultrasound‐mediated hydrogel delivery platform HA‐F127@Ti‐MOF‐Au/PEG‐TK‐DOX/PFD (abbr. HFTiDP) based on a “sonogenetic‐like technology” is developed, which encapsulates sonosensitizer (Ti‐MOF‐Au), chemotherapeutic prodrug (PEG‐TK‐DOX), and ECM‐solubilizing drug pirfenidone (PFD), to achieve high tissue penetration and endogenous intracellular regulation of IME. More importantly, exogenous ultrasound stimulation combined with a hydrogel delivery platform can affect drug resistance‐related gene/protein expressions and influence signal transduction pathways in the immune microenvironment, leading to promoting TAAs release to activate immunity, achieving high efficacy in either pancreatic or triple‐negative breast cancer (TNBC), and remarkably inhibiting lung metastasis and splenomegaly. Overall, this work provides a novel strategy for an ultrasound‐mediated niche‐like delivery platform that offers high efficacy and biosafety in localized cancer therapy.
Funder
National Natural Science Foundation of China
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials