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Synthesis of Carboxy-Dimethylmaleic Amide Linked Polymer Conjugate Based Ultra-pH-sensitive Nanoparticles for Enhanced Antitumor Immunotherapy. | LitMetric

Synthesis of Carboxy-Dimethylmaleic Amide Linked Polymer Conjugate Based Ultra-pH-sensitive Nanoparticles for Enhanced Antitumor Immunotherapy.

ACS Macro Lett

Department of Chemistry, Institute for Quantitative Health Science and Engineering, and Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan 48824, United States.

Published: November 2020

AI Article Synopsis

Article Abstract

Cytotoxic T lymphocytes (CTLs) are an important tool for anticancer immunotherapy. To elicit powerful CTL activities, ultra-pH-sensitive nanoparticles (NPs) based on methoxy poly(ethylene glycol)--[poly(diisopropylamino)ethyl methacrylate] have been synthesized as a vaccine delivery platform. A representative CTL epitope, ovalbumin (OVA) peptide antigen, was covalently conjugated to the polymer backbone through an acid responsive carboxy-dimethylmaleic amide linker (CDM) resulting in polymer P-CDM-OVA. Interestingly, while the P-CDM-OVA released OVA peptide slowly in a pH 6.4 buffer, the addition of bovine serum albumin (BSA) mimicking proteins encountered in a cellular and/or environment significantly accelerated the release process. Successful cell surface presentation of OVA was observed when P-CDM-OVA based ultra-pH-sensitive particles were incubated with antigen presenting cells. These P-CDM-OVA NPs greatly enhanced CTL responses compared to the free peptide or the previously reported acetalated dextran particles encapsulating OVA. The P-CDM was also investigated for adjuvant conjugation, and the coadministration of P-CDM-OVA and the P-CDM-adjuvant conjugate NPs further improved CTL responses and effectively reduced tumor growth in mice. Thus, the CDM linked polymer presents a promising platform for anticancer immunotherapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676757PMC
http://dx.doi.org/10.1021/acsmacrolett.0c00755DOI Listing

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