Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel
Abstract
A targeted intracellular delivery system of paclitaxel (PTX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for PTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 mm reducing agent, glutathione. In vitro drug release studies showed that the PTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of PTX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis. In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs.
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DLS showed its usefulness in defining micelles structural modifications in response to temperature, pH, enzymes, and light.
“Concerning stimuli-responsive micelles, DLS showed its usefulness in defining micelles structural modifications in response to temperature [141][142][143], pH [143,144], enzymes [145,146] and light [141,147].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [147]
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- Authors
- Li, J., Huo, M., Wang, J., Zhou, J., Mohammad, J. M., Zhang, Y., Zhu, Q., Waddad, A. Y., & Zhang, Q.
- Affiliations
- China Pharmaceutical University (CN)
- Mustansiriyah University (IQ)
- State Key Laboratory of Natural and Biomimetic Drugs (CN)
- Corresponding author
- Huo, Meirong
- Zhou, Jianping
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 33
- Issue
- 7
- Pages
- 2310-2320
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W1976073542
- Cited by
- 468
- References
- 39
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 14 · 2023: 28 · 2022: 34 · 2021: 34 · 2020: 28 · 2019: 32 · 2018: 55 · 2017: 45 · 2016: 56 · 2015: 45 · 2014: 36 · 2013: 24 · 2012: 10
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- paclitaxel, intracellular drug delivery, glutathione-responsive release, tumor targeting, breast adenocarcinoma, MDA-MB-231 cells, amphiphilic conjugates, anticancer drug carriers
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Deoxycholic Acid, Drug Carriers, Female, Fluorescent Dyes, Glutathione, Humans, Hyaluronic Acid, Materials Testing, Micelles, Neoplasms, Experimental, Oxazines, Oxidation-Reduction, Molecular Structure, Drug Delivery Systems, Paclitaxel, Microscopy, Atomic Force, Cell Line, Tumor, Mice
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