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Cited by 27

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Vitamin-H Channeled Self-Therapeutic P-gp Inhibitor Curcumin-Derived Nanomicelles for Targeting the Tumor Milieu by pH- and Enzyme-Triggered Hierarchical Disassembly

Das, Manita, Joshi, Apeksha, Devkar, Ranjitsinh, Seshadri, Sriram, Thakore, Sonal·2022·Bioconjugate Chemistry
DOI 10.1021/acs.bioconjchem.1c00614
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Abstract

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 in vitro release studies revealed a controlled release of DOX under acidic conditions and curcumin release in response to the enzyme. The value of the combination index calculated on HepG2 cells was found to be in vivo evidence on a hepatocellular carcinoma (HCC)-induced nude mice model. An evident decrease in MMP-2, MMP-9, and α-fetoprotein (AF…

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Metadata

Authors
Das, M., Joshi, A., Devkar, R., Seshadri, S., & Thakore, S.
Venue
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Published
2022-01-11
Volume
33
Issue
2
Pages
369-385
ISSN
  • 1043-1802
  • 1520-4812
DOI
10.1021/acs.bioconjchem.1c00614
Cited by
27
References
0
Language
en
Licence
Funders
Solvay Research and Innovation Center (GCU-4/S.R.F./93/#10154/444)

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