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Publication
Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cells
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Advisor(s)
Abstract(s)
Developing new easy-to-prepare functional drug delivery nanosystems with
good storage stability, low hemotoxicity, as well as controllable drug delivery
property, has attracted great attention in recent years. In this work, a
cholesterol-based prodrug nanodelivery system is prepared by self-assembly
of cholesterol-doxorubicin prodrug conjugates (Chol-Dox) and tocopherol
polyethylene glycol succinate (TPGS) using thin-film hydration method. The
Chol-Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form
nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface
zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m
PBS, 16 days). The Chol-Dox/TPGS assemblies show low hemotoxicity and
different cytotoxicity profiles in breast cancer cells (MCF-7 and MDA-MB-231),
which are largely dependent on the molar ratio of Chol-Dox and TPGS. The
Chol-Dox/TPGS assemblies tend to enter into MCF-7 and MDA-MB-231 cells
through non-Clathrin-mediated multiple endocytosis and
lysosome-dependent uptake pathways, moreover, these nanoassemblies
demonstrate lysosome-dependent intracellular localization, which is different
from that of free DOX (nuclear localization). The results demonstrate that the
Chol-Dox/TPGS assemblies are promising cholesterol-based prodrug
nanomaterials for breast cancer chemotherapy.
Practical Applications: This work demonstrates a lipid prodrug-based
nanotherapeutic system. Herein the Chol-Dox/TPGS nanoassemblies could
serve as promising and controllable cholesterol-based prodrug
nanomaterials/nano-formulations for potential breast cancer chemotherapy.
Description
Keywords
Self-assembly of cholesterol-doxorubicin Prodrug-based nanoparticles Enhanced cellular uptake Lysosome-dependent Breast cancer cells Cholesterol-doxorubicin . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira
Citation
Olim, F., Neves, A. R., Vieira, M., Tomás, H., & Sheng, R. (2021). Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cells. European Journal of Lipid Science and Technology, 123(5), 2000337. https://doi.org/10.1002/ejlt.202000337
Publisher
Wiley