Biodegradable reduction-responsive polymeric micelles for enhanced delivery of melphalan to retinoblastoma cells
Abstract
Melphalan (MEL) is an effective chemotherapeutic agent for treatment of retinoblastoma (Rb) which is the most common childhood malignancy. However, the inherent cardiopulmonary toxicity and hazardous integration limit its therapeutic effect on RB. N-Acetylheparosan (AH), a natural heparin-like polysaccharide in mammals with long circulation effect and good biocompatibility, was linked by d-α-tocopherol acid succinate (VES) via and cystamine (CYS) to synthesize reduction-responsive N-acetylheparosan-CYS-Vitamin E succinate (AHV) copolymers. In addition, CYS was replaced by adipic acid dihydrazide (ADH) to obtain a control of non-reduction-responsive polymers N-acetylheparosan-ADH-Vitamin E succinate (ADV). MEL-loaded AHV micelles (MEL/AHV) as well as ADV micelles (MEL/ADV) were prepared with small particle size and high drug loading content. In vitro drug release showed that MEL/AHV micelles presented obvious reduction-triggered release behavior compared with MEL/ADV. In vitro antitumor effects were investigated using WERI-Rb-1 retinoblastoma cells. Cytotoxicity experiments showed that the IC 50 of MEL/AHV was significantly lower than that of free MEL and MEL/ADV, suggesting that MEL/AHV enhanced the cytotoxicity against retinoblastoma cells. Furthermore, MEL/AHV micelles were more easily uptaken by multiple pathways compared with MEL/ADV and free MEL. Therefore, MEL/AHV might be a potential delivery system for enhanced delivery of melphalan to Rb cells.
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MEL/AHV micelles exhibited obvious reduction sensitivity, resulting in enhanced drug release within tumor cells.
“In vitro release experiments demonstrated that MEL/AHV micelles exhibited obvious reduction sensitivity, resulting in enhanced drug release within tumor cells.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [184]
MEL/AHV micelles were internalized into tumor cells through multiple pathways, with macropinocytosis playing a predominant role.
“Moreover, MEL/AHV micelles were internalized into tumor cells through multiple pathways, with macropinocytosis playing a predominant role [184].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [184]
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- Authors
- Li, J., Wang, J., Zhang, X., Xia, X., & Zhang, C.
- Affiliations
- Wuxi Fourth People's Hospital (CN)
- Corresponding author
- Li, Jia
- ORCID
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 141
- Pages
- 997-1003
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2972563505
- Cited by
- 17
- References
- 33
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- melphalan, retinoblastoma, polymeric micelles, vitamin E succinate, cystamine, adipic acid dihydrazide, heparin-like polysaccharides, drug release, cytotoxicity, biodegradable polymers
- MeSH terms
- Cell Survival, Humans, Melphalan, Micelles, Models, Biological, Magnetic Resonance Spectroscopy, Polymers, Retinoblastoma, Antineoplastic Agents, Alkylating, Cell Line, Tumor, Drug Liberation
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