Block and Random Copolymers Bearing Cholic Acid and Oligo(ethylene glycol) Pendant Groups: Aggregation, Thermosensitivity, and Drug Loading
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A series of block and random copolymers consisting of oligo(ethylene glycol) and cholic acid pendant groups were synthesized via ring-opening metathesis polymerization of their norbornene derivatives. These block and random copolymers were designed to have similar molecular weights and comonomer ratios; both types of copolymers showed thermosensitivity in aqueous solutions with similar cloud points. The copolymers self-assembled into micelles in water as shown by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameter of the micelles formed by the block copolymer is much larger and exhibited a broad and gradual shrinkage from 20 to 54 °C below its cloud point, while the micelles formed by the random copolymers are smaller in size but exhibited some swelling in the same temperature range. Based on in vitro drug release studies, 78% and 24% paclitaxel (PTX) were released in 24 h from micelles self-assembled by the block and random copolymers, respectively. PTX-loaded micelles formed by the block and random copolymers exhibited apparent antitumor efficacy toward the ovarian cancer cells with a particularly low half-maximal inhibitory concentration (IC50) of 27.4 and 40.2 ng/mL, respectively. Cholic acid-based micelles show promise as a versatile and potent platform for cancer chemotherapy.
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Previous studies have highlighted that not only composition, but also architecture and monomer distributions of copolymers could strongly affect their thermal, mechanical and aggregation properties.
“Previous studies have highlighted that not only the composition, but also the architecture and monomers distributions of copolymers could strongly affect their thermal, mechanical and aggregation properties [36,37,38].”
From Thermo-Rheological and Shape Memory Properties of Block and Random Copolymers of Lactide and ε-Caprolactone (2021) · cites this paper as [36]
In Results and Discussion, “Self-Assembly of Block and Random Copolymers” (page unavailable), block and random copolymers of similar composition form micelles with different sizes and temperature-dependent behavior, supporting an effect of monomer distribution on aggregation. The same section says their cloud points do not differ significantly, and the paper does not establish an effect on mechanical properties. Thus it supports only part of the broad claim. (LLM, conf=0.88)
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- Authors
- Shao, Y., Jia, Y.-G., Shi, C., Luo, J., & Zhu, X. X.
- Affiliations
- Université de Montréal (CA)
- SUNY Upstate Medical University (US)
- Corresponding author
- Zhu, X. X.
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-04-11
- Volume
- 15
- Issue
- 5
- Pages
- 1837-1844
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- PMC
- PMC4020593
- OpenAlex
- W2330307975
- Cited by
- 67
- References
- 50
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 13 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 8 · 2015: 3 · 2014: 2
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biomacromolecules (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Research Foundation
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- National Institutes of Health
- Natural Sciences and Engineering Research Council of Canada
- National Cancer Institute (R01CA140449)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Physical Sciences › Chemistry › Organic Chemistry › Surfactants and Colloidal Systems
- Keywords
- cholic acid, oligo(ethylene glycol), block copolymers, random copolymers, thermoresponsive polymers, cloud point, micelle self-assembly, paclitaxel, drug loading, controlled drug release, ovarian cancer, antitumor efficacy, ring-opening metathesis polymerization, norbornene derivatives
- MeSH terms
- Antineoplastic Agents, Cell Survival, Drug Carriers, Drug Screening Assays, Antitumor, Female, Humans, Micelles, Models, Molecular, Ovarian Neoplasms, Particle Size, Polymers, Surface Properties, Temperature, Tumor Cells, Cultured, Molecular Structure, Paclitaxel, Cholic Acid, Ethylene Glycol, Inhibitory Concentration 50, Hydrodynamics
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