Theranostics 2019; 9(4):961-973. doi:10.7150/thno.30765 This issue Cite

Research Paper

Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy

Mixiao Tan1, Weiwei Liu1, Fengqiu Liu1, Wei Zhang1, Hui Gao1, Juan Cheng1, Yu Chen2, Zhigang Wang1, Yang Cao1✉, Haitao Ran1✉

1. The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, China.
2. State Key Lab of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

Citation:
Tan M, Liu W, Liu F, Zhang W, Gao H, Cheng J, Chen Y, Wang Z, Cao Y, Ran H. Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy. Theranostics 2019; 9(4):961-973. doi:10.7150/thno.30765. https://www.thno.org/v09p0961.htm
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Abstract

Graphic abstract

Background: 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.

Keywords: silk fibroin coating, amorphous calcium carbonate, acid-responsive, premature drug release, cancer chemotherapy


Citation styles

APA
Tan, M., Liu, W., Liu, F., Zhang, W., Gao, H., Cheng, J., Chen, Y., Wang, Z., Cao, Y., Ran, H. (2019). Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy. Theranostics, 9(4), 961-973. https://doi.org/10.7150/thno.30765.

ACS
Tan, M.; Liu, W.; Liu, F.; Zhang, W.; Gao, H.; Cheng, J.; Chen, Y.; Wang, Z.; Cao, Y.; Ran, H. Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy. Theranostics 2019, 9 (4), 961-973. DOI: 10.7150/thno.30765.

NLM
Tan M, Liu W, Liu F, Zhang W, Gao H, Cheng J, Chen Y, Wang Z, Cao Y, Ran H. Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy. Theranostics 2019; 9(4):961-973. doi:10.7150/thno.30765. https://www.thno.org/v09p0961.htm

CSE
Tan M, Liu W, Liu F, Zhang W, Gao H, Cheng J, Chen Y, Wang Z, Cao Y, Ran H. 2019. Silk Fibroin-Coated Nanoagents for Acidic Lysosome Targeting by a Functional Preservation Strategy in Cancer Chemotherapy. Theranostics. 9(4):961-973.

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