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Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy
Tan, Mixiao; Liu, Weiwei; Liu, Fengqiu; Zhang, Wei; Gao, Hui; Cheng, Juan; Chen, Yu; Wang, Zhigang; Cao, Yang; Ran, Haitao
2019
Source PublicationTHERANOSTICS
ISSN1838-7640
Volume9Issue:4Pages:961
SubtypeArticle
AbstractBackground: Premature drug leakage and inefficient cellular uptake are stand out as considerable hurdles for low drug delivery efficiency in tumor chemotherapy. Thus, we established a novel drug delivery and transportation strategy mediated by biocompatible silk fibroin (SF)-coated nanoparticles to overcome these therapeutic hurdles. Methods: we first synthesised a TME-responsive biocompatible nanoplatform constructed of amorphous calcium carbonate (ACC) cores and SF shells for enhanced chemotherapy by concurrently inhibiting premature drug release, achieving lysosome-targeted explosion and locally sprayed DOX, and monitoring via PAI, which was verified both in vitro and in vivo. Results: The natural SF polymer first served as a "gatekeeper" to inhibit a drug from prematurely leaking into the circulation was demonstrated both in vitro and in vivo. Upon encountering TMEs and targeting to the acidic pH environments of lysosomes, the sensitive ACC nanoparticles were gradually degraded, eventually generating a large amount of Ca2+ and CO2, resulting in lysosomal collapse, thus preventing both the efflux of DOX from cancer cells and the protonation of DOX within the lysosome, releasing multiple hydrolytic enzyme to cytoplasm, exhibiting the optimal therapeutic dose and remarkable synergetic therapeutic performance. In particular, CO2 gas generated by the pH response of ACC nanocarriers demonstrated their imaging capability for PAI, providing the potential for quantifying and guiding drug release in targets. Conclusion: In this work, we constructed TME-responsive biocompatible NPs by coating DOX-preloaded ACC-DOX clusters with SF via a bioinspired mineralization method for efficient therapeutics. This functional lysosome-targeted preservation-strategy-based therapeutic system could provid novel insights into cancer chemotherapy.
Keywordsilk fibroin coating amorphous calcium carbonate acid-responsive premature drug release cancer chemotherapy
DOI10.7150/thno.30765
Language英语
WOS Research AreaResearch & Experimental Medicine
PublisherIVYSPRING INT PUBL
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sic.ac.cn/handle/331005/27428
Collection中国科学院上海硅酸盐研究所
Recommended Citation
GB/T 7714
Tan, Mixiao,Liu, Weiwei,Liu, Fengqiu,et al. Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy[J]. THERANOSTICS,2019,9(4):961.
APA Tan, Mixiao.,Liu, Weiwei.,Liu, Fengqiu.,Zhang, Wei.,Gao, Hui.,...&Ran, Haitao.(2019).Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy.THERANOSTICS,9(4),961.
MLA Tan, Mixiao,et al."Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy".THERANOSTICS 9.4(2019):961.
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