ACS applied materials & interfacesJul 27, 2026

Carefully Designed Polymer Carriers for Effective PTEN mRNA Treatment of Non-Small Cell Lung Cancer

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 28, 2026

Abstract

The copolymer PEG₄₅-b-P(AAPBA₂₁-co-DMAPMA₁₈) restored PTEN expression and inhibited tumor growth by 81.0% relative to the PBS control group.

Restoring PTEN may offer a therapeutic strategy for nonsmall cell lung cancer (NSCLC).
mRNA-based therapy could provide high specificity and excellent safety compared to traditional approaches.
The diblock copolymer design facilitates effective delivery of PTEN mRNA in laboratory and animal models.
The polymer's structure includes a stealth PEG block and a cationic binding block that enhance cellular uptake.
Functionalization with folic acid improves the copolymer's ability to restore PTEN expression and inhibit tumor growth.
No significant toxicity was observed in the tested conditions.

Simplified

Restoring the tumor suppressor PTEN (phosphatase and tensin homolog) offers a promising therapeutic strategy for nonsmall cell lung cancer (NSCLC). In particular, mRNA-based therapy provides a compelling alternative to small molecules and DNA-based gene therapy, combining high specificity with an excellent safety profile. However, its clinical translation hinges on the development of safe and efficient delivery systems. In this study, we present a rationally designed diblock copolymer that mediates highly effective PTEN mRNA delivery both in vitro and in vivo. The copolymer consists of a stealth PEG block and a cationic binding block, with precisely engineered 3-acrylamidophenylboronic acid (AAPBA) and N-(3-dimethylaminopropyl) methacrylamide (DMAPMA) units. Following optimization of the PEG chain length, the structure PEG₄₅-b-P(AAPBA₂₁-co-DMAPMA₁₈) achieved a critical balance of delivery properties, leading to enhanced cellular uptake, facilitated endosomal escape, and enabled mRNA release for protein translation. When further functionalized with folic acid (FA), the copolymer successfully restored PTEN expression and inhibited tumor growth (81.0% relative to the PBS control group) in vivo, with no significant toxicity observed under the tested conditions. We anticipate that this block copolymer-based PTEN mRNA delivery platform could provide a promising new approach for the treatment of NSCLC.

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Carefully Designed Polymer Carriers for Effective PTEN mRNA Treatment of Non-Small Cell Lung Cancer

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