Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy

Rutika A. Kokate; Pankaj Chaudhary; Xiangle Sun; Sanjay I. Thamake; Sayantan Maji; Rahul Chib; Jamboor K. Vishwanatha; Harlan P. Jones

doi:10.2217/nnm.15.213

Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy

Rutika A. Kokate, Pankaj Chaudhary, Xiangle Sun, Sanjay I. Thamake, Sayantan Maji, Rahul Chib, Jamboor K. Vishwanatha, Harlan P. Jones

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

28 Scopus citations

Abstract

Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy. Materials & methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy. Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses. Conclusion: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

Original language	English
Pages (from-to)	479-494
Number of pages	16
Journal	Nanomedicine
Volume	11
Issue number	5
DOIs	https://doi.org/10.2217/nnm.15.213
State	Published - Mar 2016

Keywords

DCs
NP
breast cancer
cancer vaccines
dendritic cells
immunotherapy
nanoparticle

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10.2217/nnm.15.213

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@article{5dcdc76bcc544a45a8a2e283e2e34b97,

title = "Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy",

abstract = "Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy. Materials & methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy. Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses. Conclusion: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.",

keywords = "DCs, NP, breast cancer, cancer vaccines, dendritic cells, immunotherapy, nanoparticle",

author = "Kokate, {Rutika A.} and Pankaj Chaudhary and Xiangle Sun and Thamake, {Sanjay I.} and Sayantan Maji and Rahul Chib and Vishwanatha, {Jamboor K.} and Jones, {Harlan P.}",

note = "Funding Information: The authors would like to thank Dr A Darehshouri from Electron Microscopy Core Facility, UT Southwestern Medical Center for help with the SEM imaging. This research was supported in part by National Institute on Minority Health and Health Disparities Grant 1P20 MD006882 (to JK Vishwanatha), Department of Molecular and Medical Genetics at UNTHSC and Predoctoral Bridge Funding Grant (R16138) from UNTHSC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2016 Future Medicine Ltd.",

year = "2016",

month = mar,

doi = "10.2217/nnm.15.213",

language = "English",

volume = "11",

pages = "479--494",

journal = "Nanomedicine",

issn = "1743-5889",

publisher = "Future Medicine Ltd.",

number = "5",

}

TY - JOUR

T1 - Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy

AU - Kokate, Rutika A.

AU - Chaudhary, Pankaj

AU - Sun, Xiangle

AU - Thamake, Sanjay I.

AU - Maji, Sayantan

AU - Chib, Rahul

AU - Vishwanatha, Jamboor K.

AU - Jones, Harlan P.

N1 - Funding Information: The authors would like to thank Dr A Darehshouri from Electron Microscopy Core Facility, UT Southwestern Medical Center for help with the SEM imaging. This research was supported in part by National Institute on Minority Health and Health Disparities Grant 1P20 MD006882 (to JK Vishwanatha), Department of Molecular and Medical Genetics at UNTHSC and Predoctoral Bridge Funding Grant (R16138) from UNTHSC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2016 Future Medicine Ltd.

PY - 2016/3

Y1 - 2016/3

N2 - Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy. Materials & methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy. Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses. Conclusion: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

AB - Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy. Materials & methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy. Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses. Conclusion: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

KW - DCs

KW - NP

KW - breast cancer

KW - cancer vaccines

KW - dendritic cells

KW - immunotherapy

KW - nanoparticle

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U2 - 10.2217/nnm.15.213

DO - 10.2217/nnm.15.213

M3 - Article

C2 - 26892440

AN - SCOPUS:84962578587

SN - 1743-5889

VL - 11

SP - 479

EP - 494

JO - Nanomedicine

JF - Nanomedicine

IS - 5

ER -

Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy

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