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Nano Research 2023, 16(7): 9804-9814 https://doi.org/10.1007/s12274-023-5665-3
Research Article | Issue | Published: 11 April 2023

Light-activated arginine-rich peptide-modified nanoparticles for deep-penetrating chemo-photo-immunotherapy of solid tumor

Show Author's Information Yonghua Gong1,§,  Jinyang Zhang1,§,  Yan Lu1,  Dong Wan2,  Jie Pan2( ),  Guilei Ma1( )
Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China
School of Environmental and Chemical Engineering, Tiangong University, Tianjin 300387, China

§ Yonghua Gong and Jinyang Zhang contributed equally to this work.

Keywords:
transcytosis, deep penetration, light-activated nanoparticles, chemo-photo-immunotherapy, solid tumor
Topics:
ImmunologyMedical nanotechnology
Cite this article:
Gong Y, Zhang J, Lu Y, et al. Light-activated arginine-rich peptide-modified nanoparticles for deep-penetrating chemo-photo-immunotherapy of solid tumor. Nano Research, 2023, 16(7): 9804-9814. https://doi.org/10.1007/s12274-023-5665-3
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Abstract Full text Electronic supplementary material About this article

Poor permeation of drugs and “immune-cold” tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment. Here, light-activated penetrable nanoparticles (PEG-VAL&DOX&ICG@RNPs) for co-delivery of the chemotherapeutic drug doxorubicin (DOX), the photosensitizer agent indocyanine green (ICG), and the angiotensin II receptor blockers valsartan (VAL) were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor. Studies showed that under the first-wave of laser irradiation, the polyethylene glycol (PEG) hydrophilic layer as an “inert” surface could detach from the nanoparticles, release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway. When exposed to the second-wave of laser irradiation, the synergistic chemo-photo-immunotherapy can be achieved. As expected, in 4T1 tumor-bearing mice, PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors, down-regulate α-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors, induce dendritic cells (DCs) maturation, and promote intratumoral infiltration of cytotoxic T lymphocytes. Moreover, combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo. This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of “immune-cold” solid tumor treatment.


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Electronic supplementary material
About this article

Light-activated arginine-rich peptide-modified nanoparticles for deep-penetrating chemo-photo-immunotherapy of solid tumor

Show Author's information Yonghua Gong1,§, Jinyang Zhang1,§, Yan Lu1, Dong Wan2, Jie Pan2( ), Guilei Ma1( )
Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China
School of Environmental and Chemical Engineering, Tiangong University, Tianjin 300387, China

§ Yonghua Gong and Jinyang Zhang contributed equally to this work.

Abstract

Poor permeation of drugs and “immune-cold” tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment. Here, light-activated penetrable nanoparticles (PEG-VAL&DOX&ICG@RNPs) for co-delivery of the chemotherapeutic drug doxorubicin (DOX), the photosensitizer agent indocyanine green (ICG), and the angiotensin II receptor blockers valsartan (VAL) were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor. Studies showed that under the first-wave of laser irradiation, the polyethylene glycol (PEG) hydrophilic layer as an “inert” surface could detach from the nanoparticles, release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway. When exposed to the second-wave of laser irradiation, the synergistic chemo-photo-immunotherapy can be achieved. As expected, in 4T1 tumor-bearing mice, PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors, down-regulate α-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors, induce dendritic cells (DCs) maturation, and promote intratumoral infiltration of cytotoxic T lymphocytes. Moreover, combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo. This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of “immune-cold” solid tumor treatment.

Keywords: transcytosis, deep penetration, light-activated nanoparticles, chemo-photo-immunotherapy, solid tumor

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Publication history
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Acknowledgements

Publication history

Received: 29 January 2023
Revised: 02 March 2023
Accepted: 12 March 2023
Published: 11 April 2023
Issue date: July 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

We acknowledge financial support from National Natural Science Foundation of China (Nos. 82172089, 22178270 and 22078246), the Fundamental Research Funds for the Central Universities (No. 2019PT320028), and CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-058).

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