A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy

Chuangnian Zhang; Ju Zhang; Gaona Shi; Huijuan Song; Shengbin Shi; Xiuyuan Zhang; Pingsheng Huang; Zhihong Wang; Weiwei Wang; Chun Wang; Deling Kong; Chen Li

doi:10.1021/acs.molpharmaceut.7b00015

A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy

Chuangnian Zhang, Ju Zhang, Gaona Shi, Huijuan Song, Shengbin Shi, Xiuyuan Zhang, Pingsheng Huang, Zhihong Wang, Weiwei Wang, Chun Wang, Deling Kong, Chen Li

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8⁺ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3⁺CD8⁺T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8⁺ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.

Original language	English (US)
Pages (from-to)	1760-1770
Number of pages	11
Journal	Molecular pharmaceutics
Volume	14
Issue number	5
DOIs	https://doi.org/10.1021/acs.molpharmaceut.7b00015
State	Published - May 1 2017

Bibliographical note

Funding Information:
This work was financially supported by the National Natural Science Foundation of China (21604095, 31300732, 51373199 31400833, 1670977), China Postdoctoral Science Foundation (2015M580066), Program for Innovative Research Team in Peking Union Medical College, CAMS Initiative for Innovative Medicine (2016-I2M-3-022), and the Open Fund of Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University (201606).

Publisher Copyright:
© 2017 American Chemical Society.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

antigen delivery
cross-presentation
endosome escape
immunotherapy
photochemical internalization

Access

10.1021/acs.molpharmaceut.7b00015

Fingerprint Dive into the research topics of 'A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy'. Together they form a unique fingerprint.

Cite this

A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy. / Zhang, Chuangnian; Zhang, Ju; Shi, Gaona; Song, Huijuan; Shi, Shengbin; Zhang, Xiuyuan; Huang, Pingsheng; Wang, Zhihong; Wang, Weiwei; Wang, Chun; Kong, Deling; Li, Chen.

In: Molecular pharmaceutics, Vol. 14, No. 5, 01.05.2017, p. 1760-1770.

Research output: Contribution to journal › Article › peer-review

Zhang, Chuangnian ; Zhang, Ju ; Shi, Gaona ; Song, Huijuan ; Shi, Shengbin ; Zhang, Xiuyuan ; Huang, Pingsheng ; Wang, Zhihong ; Wang, Weiwei ; Wang, Chun ; Kong, Deling ; Li, Chen. / A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy. In: Molecular pharmaceutics. 2017 ; Vol. 14, No. 5. pp. 1760-1770.

@article{299b4bad9b114d9ca0e8df4f676cd01f,

title = "A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy",

abstract = "In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.",

keywords = "antigen delivery, cross-presentation, endosome escape, immunotherapy, photochemical internalization",

author = "Chuangnian Zhang and Ju Zhang and Gaona Shi and Huijuan Song and Shengbin Shi and Xiuyuan Zhang and Pingsheng Huang and Zhihong Wang and Weiwei Wang and Chun Wang and Deling Kong and Chen Li",

note = "Funding Information: This work was financially supported by the National Natural Science Foundation of China (21604095, 31300732, 51373199 31400833, 1670977), China Postdoctoral Science Foundation (2015M580066), Program for Innovative Research Team in Peking Union Medical College, CAMS Initiative for Innovative Medicine (2016-I2M-3-022), and the Open Fund of Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University (201606). Publisher Copyright: {\textcopyright} 2017 American Chemical Society. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

year = "2017",

month = may,

day = "1",

doi = "10.1021/acs.molpharmaceut.7b00015",

language = "English (US)",

volume = "14",

pages = "1760--1770",

journal = "Molecular Pharmaceutics",

issn = "1543-8384",

number = "5",

}

TY - JOUR

T1 - A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy

AU - Zhang, Chuangnian

AU - Zhang, Ju

AU - Shi, Gaona

AU - Song, Huijuan

AU - Shi, Shengbin

AU - Zhang, Xiuyuan

AU - Huang, Pingsheng

AU - Wang, Zhihong

AU - Wang, Weiwei

AU - Wang, Chun

AU - Kong, Deling

AU - Li, Chen

N1 - Funding Information: This work was financially supported by the National Natural Science Foundation of China (21604095, 31300732, 51373199 31400833, 1670977), China Postdoctoral Science Foundation (2015M580066), Program for Innovative Research Team in Peking Union Medical College, CAMS Initiative for Innovative Medicine (2016-I2M-3-022), and the Open Fund of Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University (201606). Publisher Copyright: © 2017 American Chemical Society. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.

AB - In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.

KW - antigen delivery

KW - cross-presentation

KW - endosome escape

KW - immunotherapy

KW - photochemical internalization

UR - http://www.scopus.com/inward/record.url?scp=85018406770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018406770&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.7b00015

DO - 10.1021/acs.molpharmaceut.7b00015

M3 - Article

C2 - 28296410

AN - SCOPUS:85018406770

VL - 14

SP - 1760

EP - 1770

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 5

ER -

A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy

Abstract

Bibliographical note

Keywords

Access

Other files and links

Cite this