Dinitrophenol-Hyaluronan Conjugates as Multivalent Antibody-Recruiting Glycopolymers for Targeted Cancer Immunotherapy.

Abstract

Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG3 -DNP]8 , showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, we found that HA-[PEG3 -DNP]8 significantly inhibited the xenograft tumor growth of Babl/c nude mice bearing triple negative breast cancer cells, while it did not cause detectable histological cytotoxicity. Given the easy access of this type of natural glycopolymer and the practical synthesis approach, these MARGs provide promising immunotherapeutics for cancer immunotherapy.

• Authors: Han Lin, Kun Zhou, Dan Li, Haofei Hong, Yuntian Xie, Liang Gong, Yu Shen, Zhifang Zhou, Jie Shi, Zhimeng Wu
• Journal: ChemMedChem (ChemMedChem) Vol. 16 Issue 19 Pg. 2960-2968 (10 06 2021) ISSN: 1860-7187 [Electronic] Germany
• PMID: 34235861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents
• Dinitrophenols
• Polymers
• Hyaluronic Acid

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Dinitrophenols (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Humans
• Hyaluronic Acid (chemistry, pharmacology)
• Immunotherapy
• Mammary Neoplasms, Experimental (therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Structure
• Polymers (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship