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Title: AS101-Loaded PLGA–PEG Nanoparticles for Autoimmune Regulation and Chemosensitization

Abstract

The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethyleneo, o’)tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(D,L-lactic-co-glycolic acid)- block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for anti-tumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bellshaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving optimal antimetastatic effect.

Authors:
 [1]; ORCiD logo [1];  [1];  [1]; ORCiD logo [1]
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  1. Bar-Ilan Univ., Ramat-Gan (Israel)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1544701
Report Number(s):
LA-UR-19-23090
Journal ID: ISSN 2576-6422
Grant/Contract Number:  
89233218CNA000001
Resource Type:
Accepted Manuscript
Journal Name:
ACS Applied Bio Materials
Additional Journal Information:
Journal Volume: 2; Journal Issue: 5; Journal ID: ISSN 2576-6422
Publisher:
ACS Publications
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Material Science

Citation Formats

Mishra, Rahul Kumar, Kumar, Vijay Bhooshan, Monteran, Lea, Sredni, Benjamin, and Gedanken, Aharon. AS101-Loaded PLGA–PEG Nanoparticles for Autoimmune Regulation and Chemosensitization. United States: N. p., 2019. Web. doi:10.1021/acsabm.9b00200.
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Mishra, Rahul Kumar, Kumar, Vijay Bhooshan, Monteran, Lea, Sredni, Benjamin, & Gedanken, Aharon. AS101-Loaded PLGA–PEG Nanoparticles for Autoimmune Regulation and Chemosensitization. United States. https://doi.org/10.1021/acsabm.9b00200
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Mishra, Rahul Kumar, Kumar, Vijay Bhooshan, Monteran, Lea, Sredni, Benjamin, and Gedanken, Aharon. Fri . "AS101-Loaded PLGA–PEG Nanoparticles for Autoimmune Regulation and Chemosensitization". United States. https://doi.org/10.1021/acsabm.9b00200. https://www.osti.gov/servlets/purl/1544701.
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@article{osti_1544701,
title = {AS101-Loaded PLGA–PEG Nanoparticles for Autoimmune Regulation and Chemosensitization},
author = {Mishra, Rahul Kumar and Kumar, Vijay Bhooshan and Monteran, Lea and Sredni, Benjamin and Gedanken, Aharon},
abstractNote = {The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethyleneo, o’)tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(D,L-lactic-co-glycolic acid)- block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for anti-tumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bellshaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving optimal antimetastatic effect.},
doi = {10.1021/acsabm.9b00200},
journal = {ACS Applied Bio Materials},
number = 5,
volume = 2,
place = {United States},
year = {Fri Apr 12 00:00:00 EDT 2019},
month = {Fri Apr 12 00:00:00 EDT 2019}
}
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https://doi.org/10.1021/acsabm.9b00200
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