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  3. Biodegradable silica nanocapsules enable efficient nuclear-targeted delivery of native proteins for cancer therapy

Biodegradable silica nanocapsules enable efficient nuclear-targeted delivery of native proteins for cancer therapy

  • Biomaterials. 2023 Mar:294:122000. doi: 10.1016/j.biomaterials.2023.122000.
Wei Du 1,  Shubo Du 2,  Xiao Dong 3,  Hua Bai 4,  Jiamin Jiang 4,  Shiping Hao 4,  Fen Yang 5,  Qicai Xiao 5,  Bei Zhang 6,  Jingyan Ge 6,  Liqian Gao 5,  Lin Li 7,  Shao Q Yao 8,  Wei Huang 9
Affiliations

Affiliations

  • 1 Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China.
  • 2 Department of Chemistry, National University of Singapore, 4 Science Drive 2, Block S9, Singapore 117544, Singapore; School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
  • 3 Department of Chemistry, National University of Singapore, 4 Science Drive 2, Block S9, Singapore 117544, Singapore.
  • 4 Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an 710072, China.
  • 5 School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.
  • 6 College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
  • 7 Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China; Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an 710072, China; The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen 361005, Fujian, China. Electronic address: iamlli@njtech.edu.cn.
  • 8 Department of Chemistry, National University of Singapore, 4 Science Drive 2, Block S9, Singapore 117544, Singapore. Electronic address: chmyaosq@nus.edu.sg.
  • 9 Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China; Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an 710072, China; The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen 361005, Fujian, China. Electronic address: vc@nwpu.edu.cn.
PMID: 36640541 DOI: 10.1016/j.biomaterials.2023.122000
Abstract

Cell nucleus is the desired subcellular organelle of many therapeutic drugs. Although numerous nanomaterial-based methods have been developed which could facilitate nuclear-targeted delivery of small-molecule drugs, few are known to be capable of delivering exogenous native proteins. Herein, we report a convenient and highly robust approach for effective nuclear-targeted delivery of native proteins/antibodies by using biodegradable silica nanocapsules (BSNPs) that were surface-modified with different nuclear localization signals (NLS) peptides. We found that, upon gaining entry to mammalian cells via endocytosis, such nanocapsules (protein@BSNP-NLS) could effectively escape from endolysosomal vesicles with the assistance of an endosomolytic peptide (i.e., L17E), accumulate in cell nuclei and release the encapsulated protein cargo with biological activities. Cloaked with HeLa cell membrane, DNase@BSNP-NLS/L17E-M (with L17E encapsulated) homologously delivered functional proteins to Cancer cell nuclei in tumor-xenografted mice. In vitro and in vivo anti-tumor properties, such as long blood circulation time and effective tumor growth inhibition, indicate that the nuclear-targeted cell-membrane-cloaked BSNPs (DNase@BSNP-NLS/L17E-M) platform is a promising therapeutic approach to nuclear related diseases.

Keywords

Biodegradable silica nanocapsules; Cancer therapy; Endosome escape; Native protein drugs; Nuclear-targeted delivery.

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