Vitamin-H Channeled Self-Therapeutic P-gp Inhibitor Curcumin-Derived Nanomicelles for Targeting the Tumor Milieu by pH- and Enzyme-Triggered Hierarchical Disassembly
| Autor: | Manita Das, Apeksha Joshi, Ranjitsinh Devkar, Sriram Seshadri, Sonal Thakore |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Drug Carriers Carcinoma Hepatocellular Curcumin Polymers Liver Neoplasms Organic Chemistry Biomedical Engineering Biotin Mice Nude Pharmaceutical Science Bioengineering Vitamins Hydrogen-Ion Concentration Polyethylene Glycols Mice Acetals Doxorubicin Animals Humans Nanoparticles Prodrugs Micelles Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 33:369-385 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | An effective nanocarrier-mediated drug delivery to cancer cells primarily faces limitations like the presence of successive drug delivery barriers, insufficient circulation time, drug leakage, and decreased tumor penetration capacity. With the aim of addressing this paradox, a self-therapeutic, curcumin-derived copolymer was synthesized by conjugation with PEGylated biotin via enzyme- and acid-labile ester and acetal linkages. This copolymer is a prodrug of curcumin and self-assembles into ∼150-200 nm-sized nanomicelles; it is capable of encapsulating doxorubicin (DOX) and hence can be designated as self-therapeutic. pH- and enzyme-responsive linkages in the polymer skeleton assist in its hierarchical disassembly only in the tumor microenvironment. Further, the conjugation of biotin and poly(ethylene glycol) (PEG) imparts features of tumor specificity and improved circulation times to the nanocarrier. The dynamic light scattering (DLS) analysis supports this claim and demonstrates rapid swelling and disruption of micelles under acidic pH. UV-vis spectroscopy provided evidence of an accelerated acetal degradation at pH 4.0 and 5.0. The |
| Databáze: | OpenAIRE |
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