Overcoming STC2 mediated drug resistance through drug and gene co-delivery by PHB-PDMAEMA cationic polyester in liver cancer cells
Abstract
Stanniocalcin 2 (STC2) overexpression in hepatocellular carcinoma (HCC) could lead to poor prognosis, which might be due to its induced P-glycoprotein and Bcl-2 protein expression level increase. P-glycoprotein or membrane pump induced drug efflux and altered prosurvival Bcl-2 expression are key mechanisms for drug resistance leading to failure of chemotherapy in HCC. However, current strategy to overcome both P-glycoprotein and Bcl-2 protein induced drug resistance was rarely reported. In this work, we utilized an amphiphilic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) cationic polyester to encapsulate chemotherapeutic paclitaxel (PTX) in hydrophobic PHB domain and Bcl-2 convertor Nur77/ΔDBD gene (Nur77 without DNA binding domain for mitochondria localization) by formation of polyplex due to cationic PDMAEMA segment, to effectively inhibit the drug resistant HepG2/STC2 and SMCC7721/STC2 liver cancer cell growth. Thanks to the cationic nanoparticle complex formation ability and high transfection efficiency to express Bcl-2 conversion proteins, PHB-PDMAEMA/PTX@polyplex could partially impair P-glycoprotein induced PTX efflux and activate the apoptotic function of previous prosurvival Bcl-2 protein. This is the pioneer report of cationic amphiphilic polyester PHB-PDMAEMA to codeliver anticancer drug and therapeutic plasmid to overcome both pump and non-pump mediated chemotherapeutic resistance in liver cancer cells, which might be inspiring for the application of polyester in personalized cancer therapy.
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Amphiphilic polymers exhibit a lower CMC relative to small-molecule surfactants, which confers increased stability and dilution in polymeric nanomicelles.
“More importantly, amphiphilic polymers exhibit a lower CMC relative to small-molecule surfactants, which confers increased stability and dilution in polymeric nanomicelles [206].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [206]
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“More importantly, amphiphilic polymers exhibit a lower CMC relative to small-molecule surfactants, which confers increased stability and dilution in polymeric nanomicelles [206].”
- Authors
- Cheng, H., Wu, Z., Wu, C., Wang, X., Liow, S. S., Li, Z., & Wu, Y.-L.
- Affiliations
- Xiamen University (CN)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Wu, Yun-Long
- Venue
- Materials Science and Engineering C
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 83
- Pages
- 210-217
- ISSN
- 0928-4931 (ISSN-L)
- OpenAlex
- W2747917548
- Cited by
- 119
- References
- 60
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 12 · 2023: 19 · 2022: 14 · 2021: 23 · 2020: 12 · 2019: 12 · 2018: 13 · 2017: 3
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Materials Science and Engineering C (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81773661, 81773688, 21303145)
- Fundamental Research Funds for the Central Universities (20720170066)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- STC2, hepatocellular carcinoma, drug resistance, P-glycoprotein, Bcl-2, paclitaxel, Nur77, polyplexes, gene delivery, drug delivery, apoptosis, HepG2 cells
- MeSH terms
- Prohibitins, Humans, Hydroxybutyrates, Liver Neoplasms, Methacrylates, Nylons, Polyesters, Drug Delivery Systems, Paclitaxel, Hep G2 Cells
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