Intracellular Glucose‐Depriving Polymer Micelles for Antiglycolytic Cancer Treatment

A new anticancer strategy to exploit abnormal metabolism of cancer cells rather than to merely control the drug release or rearrange the tumor microenvironment is reported. An antiglycolytic amphiphilic polymer, designed considering the unique metabolism of cancer cells (Warburg effect) and aimed at...

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Bibliographic Details
Published in:Advanced materials (Weinheim) 2023-03, Vol.35 (10), p.e2207342-n/a
Main Authors: Lee, Jangwook, Kim, Kwangmeyung, Kwon, Ick Chan, Lee, Kuen Yong
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
apoptosis
cancer therapy
Chemical synthesis
Chitosan
Conjugation
Deprivation
Drug Carriers - chemistry
Drug Liberation
Glucose
Glucose - metabolism
glucose‐responsive polymers
Glycolysis
Humans
induced energy deficiency
Micelles
Neoplasms - drug therapy
nutrient deprivation
Polymers
Polymers - chemistry
Side effects
Tumor Microenvironment
Tumors
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Summary:A new anticancer strategy to exploit abnormal metabolism of cancer cells rather than to merely control the drug release or rearrange the tumor microenvironment is reported. An antiglycolytic amphiphilic polymer, designed considering the unique metabolism of cancer cells (Warburg effect) and aimed at the regulation of glucose metabolism, is synthesized through chemical conjugation between glycol chitosan (GC) and phenylboronic acid (PBA). GC‐PBA derivatives form stable micellar structures under physiological conditions and respond to changes in glucose concentration. Once the micelles accumulate at the tumor site, intracellular glucose capture occurs, and the resultant energy deprivation through the inhibition of aerobic glycolysis remarkably suppresses tumor growth without significant side effects in vivo. This strategy highlights the need to develop safe and effective cancer treatment without the use of conventional anticancer drugs. A glucose‐responsive polymer is designed, considering the unique metabolism of cancer cells. The polymer exhibits micellar‐structure stability during blood circulation and accumulates in tumor tissues. Specific binding between the polymer and intracellular glucose induces glucose deprivation in tumor cells. Glucose metabolism is particularly inhibited; the lack of energy in tumor cells is intensified, leading to tumor suppression.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.202207342