2. Academic Validation
  3. Dual-responsive bioconjugates bearing a bifunctional adaptor for robust cytosolic peptide delivery

Dual-responsive bioconjugates bearing a bifunctional adaptor for robust cytosolic peptide delivery

  • J Control Release. 2023 Feb 17;355:675-684. doi: 10.1016/j.jconrel.2023.02.014.
Xin Gao 1,  Chunyang Yuan 2,  Echuan Tan 3,  Zhan Li 4,  Yiyun Cheng 5,  Jianru Xiao 6,  Guangyu Rong 7
Affiliations

Affiliations

  • 1 Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, PR China.
  • 2 Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China.
  • 3 South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, PR China.
  • 4 College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, PR China.
  • 5 Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China. Electronic address: yycheng@mail.ustc.edu.cn.
  • 6 Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, PR China. Electronic address: jianruxiao83@163.com.
  • 7 Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, PR China; South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, PR China. Electronic address: rgy5435@163.com.
PMID: 36791993 DOI: 10.1016/j.jconrel.2023.02.014
Abstract

Peptide drugs have been successfully used for the treatment of various diseases. However, it is still challenging to develop therapeutic Peptides working on intracellular targets due to their poor membrane permeability. Here, we proposed a type of dual-responsive bioconjugates bearing a heterobifunctional adaptor containing both aldehyde and catechol moieties for efficient cytosolic peptide delivery. Hydrazine-terminated cargo Peptides were tagged to a boronated dendrimer with the help of the adaptor via dynamic acylhydrazone and catechol‑boronate linkages. The bioconjugates efficiently delivered Peptides with distinct physicochemical properties into various cells, and could release the cargo Peptides triggered by intracellular Reactive Oxygen Species and endolysosomal acidity, restoring the biofunctions of delivered Peptides. In addition, the designed complexes efficiently delivered a pro-apoptotic peptide into osteosarcoma Cancer cells and successfully inhibited the tumor growth both in vitro and in vivo. This study provides a universal and efficient platform for cytosolic therapeutic peptide delivery to intracellular targets for treating various diseases.

Keywords

Dendrimer; Dynamic covalent chemistry; Intracellular peptide delivery; Responsive polymer; Therapeutic peptides.

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