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Nano Research 2023, 16(12): 13267-13282 https://doi.org/10.1007/s12274-023-5912-7
Research Article | Issue | Published: 13 October 2023

Charge-reversible crosslinked nanoparticle for pro-apoptotic peptide delivery and synergistic photodynamic cancer therapy

Show Author's Information Haijing Qu1,2,§,  Han Chen1,2,§,  Wei Cheng1,2,  Yuqing Pan1,2,  Zhiran Duan1,2,  Yanjun Wang1,3,  Xing-Jie Liang4( ),  Xiangdong Xue1,2( )
Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China

§ Haijing Qu and Han Chen contributed equally to this work.

Keywords:
photodynamic therapy, peptide delivery, charge-reversible nanoparticle, crosslinked nanoparticle, synergistic cancer treatment
Topics:
Nano biology
Cite this article:
Qu H, Chen H, Cheng W, et al. Charge-reversible crosslinked nanoparticle for pro-apoptotic peptide delivery and synergistic photodynamic cancer therapy. Nano Research, 2023, 16(12): 13267-13282. https://doi.org/10.1007/s12274-023-5912-7
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Abstract Full text Electronic supplementary material About this article

Although anti-cancer nanotherapeutics have made breakthroughs, many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers. Here, we prepared charge-reversible crosslinked nanoparticles (PDC NPs) by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers, followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility. The resultant PDC NPs have a high drug loading of 68.3%, substantially exceeding that of 10%–15% in conventional drug delivery systems. PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy. Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption, which extensively augments oxygen-dependent photodynamic therapy (PDT). The photosensitizers around mitochondria increased along with the peptides, allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways. Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.


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Abstract
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Electronic supplementary material
About this article

Charge-reversible crosslinked nanoparticle for pro-apoptotic peptide delivery and synergistic photodynamic cancer therapy

Show Author's information Haijing Qu1,2,§, Han Chen1,2,§, Wei Cheng1,2, Yuqing Pan1,2, Zhiran Duan1,2, Yanjun Wang1,3, Xing-Jie Liang4( ), Xiangdong Xue1,2( )
Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China

§ Haijing Qu and Han Chen contributed equally to this work.

Abstract

Although anti-cancer nanotherapeutics have made breakthroughs, many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers. Here, we prepared charge-reversible crosslinked nanoparticles (PDC NPs) by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers, followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility. The resultant PDC NPs have a high drug loading of 68.3%, substantially exceeding that of 10%–15% in conventional drug delivery systems. PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy. Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption, which extensively augments oxygen-dependent photodynamic therapy (PDT). The photosensitizers around mitochondria increased along with the peptides, allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways. Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.

Keywords: photodynamic therapy, peptide delivery, charge-reversible nanoparticle, crosslinked nanoparticle, synergistic cancer treatment

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Publication history
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Acknowledgements

Publication history

Received: 11 May 2023
Revised: 08 June 2023
Accepted: 09 June 2023
Published: 13 October 2023
Issue date: December 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

The authors gratefully acknowledge the support from the National Natural Science Foundation of China (Nos. 82172084 and 81803002) and STI2030-Major Projects (No. 2022ZD0212500). Scheme is created with BioRender.com.

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