Journal
BIOMATERIALS
Volume 276, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121024
Keywords
Membrane-anchoring agents; Transformable nanoassembly; Membrane targeting cancer therapy; Tumor acidity-driven nanomedicine; Deep tumor penetration
Funding
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [51773067, 51822302]
- Program for Guangdong Introducing innovative and Entrepreneurial Teams [2017ZT07S054]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2017B030306002]
- Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
- Fundamental Research Funds for the Central Universities
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This study presents a tumor acidity-driven transformable polymeric nanoassembly for membrane-targeted photodynamic therapy, which disassembles at acidic pH to enhance penetration into tumor tissue and direct anchoring to cancer cell membrane, achieving superior tumor growth inhibition under light irradiation.
In recent years, directly damaging cell membrane therapeutic modalities have attracted great attention in the field of cancer therapy due to their critical role in guaranteeing essential cellular function. In this study, the transformable nanoassembly PEG-Ce6@PAEMA, consisting of the photosensitizer polyethylene glycol-chlorin-e6 (PEG-Ce6) and tumor pH-sensitive polymer poly(2-azepane ethyl methacrylate) (PAEMA), was developed for highly efficient membrane-targeted photodynamic therapy. The PAEMA core is rapidly protonated at the acidic tumor pH, resulting in the disassembly of PEG-Ce6@PAEMA and regeneration of PEG-Ce6. Subsequently, the resultant PEG-Ce6 with a very small size (similar to 2.6 kDa) ensures deep penetration into tumor tissue and direct and rapid anchoring to the cancer cell membrane, eventually achieving superior tumor growth inhibition under light irradiation. Thus, this tumor acidity-driven transformable polymeric nanoassembly provides a simple but efficient strategy for membrane targeting cancer therapy.
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