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Lapatinib-loaded reductive-responsive hyaluronic acid-cholesterol nanoparticles for inhibiting metastasis of uveal melanoma.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 283 (Pt 1), pp. 137028. Date of Electronic Publication: 2024 Nov 01. - Publication Year :
- 2024
-
Abstract
- Uveal melanoma (UM) is the most common intraocular primary malignancy in adults with highly metastatic characteristics. Currently, there are no effective therapies to prevent metastasis formation in UM, resulting in a poor prognosis. Herein, we report a novel lapatinib-loaded reductive-responsive nanoparticle platform prepared via the self-assembly of amphiphilic hyaluronic acid-cystamine-cholesteryl hemisuccinate conjugate to suppress the distant metastasis of UM. The platform can maintain a stable nanosphere structure in the physiological environment and effectively deliver the drug to UM tumor sites, enhancing intratumoral drug accumulation and penetration. Upon endocytosis, lapatinib-loaded nanoparticles rapidly disintegrate triggered by intracellular glutathione and release the payload, leading to considerable suppression of MuM-2B cell proliferation, invasion, and migration. Systemic administration of lapatinib-loaded nanoparticles into mice bearing lung metastases of UM resulted in significantly higher metastasis suppression compared to free lapatinib, with histological analyses indicating no detectable toxicity. This nanotherapeutic platform is expected to provide a promising approach for the safe and efficient prevention of metastasis in UM.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Cell Line, Tumor
Humans
Cholesterol chemistry
Cell Proliferation drug effects
Drug Carriers chemistry
Neoplasm Metastasis prevention & control
Cell Movement drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Oxidation-Reduction
Lung Neoplasms secondary
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Xenograft Model Antitumor Assays
Hyaluronic Acid chemistry
Lapatinib pharmacology
Lapatinib chemistry
Nanoparticles chemistry
Uveal Neoplasms drug therapy
Uveal Neoplasms pathology
Melanoma drug therapy
Melanoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 283
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 39488305
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2024.137028