1. Enhanced Tumor Site Accumulation and Therapeutic Efficacy of Extracellular Matrix-Drug Conjugates Targeting Tumor Cells.
- Author
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Chen Z, Long L, Wang J, Jiang M, Li W, Cui W, and Zou L
- Subjects
- Humans, Animals, Cell Line, Tumor, Drug Delivery Systems, Neoplasms drug therapy, Neoplasms pathology, Neoplasms metabolism, Mice, Drug Liberation, Doxorubicin pharmacology, Doxorubicin therapeutic use, Doxorubicin chemistry, Extracellular Matrix metabolism, Nanoparticles chemistry
- Abstract
The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.58%, coupled with acid-sensitive drug release characteristics. Notably, ECM-DOX nanoparticles enhance the uptake by tumor cells and possess the ability to penetrate endothelial cells and infiltrate tumor multicellular spheroids. Mechanistic insights reveal that the internalization of ECM-DOX nanoparticle is facilitated through clathrin-mediated endocytosis and macropinocytosis, intricately involving hyaluronic acid receptors and integrins. Pharmacokinetic assessments unveil a prolonged blood half-life of ECM-DOX nanoparticles at 3.65 h, a substantial improvement over the 1.09 h observed for free DOX. A sustained accumulation effect of ECM-DOX nanoparticles at tumor sites, with drug levels in tumor tissues surpassing those of free DOX by several-fold. The profound therapeutic impact of ECM-DOX nanoparticles is evident in their notable inhibition of tumor growth, extension of median survival time in animals, and significant reduction in DOX-induced cardiotoxicity. The ECM platform emerges as a promising carrier for avant-garde nanomedicines in the realm of cancer treatment., (© 2024 Wiley‐VCH GmbH.)
- Published
- 2024
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