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Cited by 169Nanoparticle-Based Drug DeliveryDrug Transport and Resistance MechanismsRNA Interference and Gene Delivery

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Role of cellular uptake in the reversal of multidrug resistance by PEG-b-PLA polymeric micelles

Xiao, Ling, Xiong, Xiaoqin, Sun, Xiaohui, Zhu, Yanhong, Yang, Hao, Chen, Huabing, Gan, Lu, Xu, Huibi, Yang, Xiangliang·2011·Biomaterials
DOI 10.1016/j.biomaterials.2011.03.071
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Abstract

Understanding the processes involved in the cellular uptake of nanoparticles is critical for developing effective nano drug delivery systems. In this paper we found that PEG-b-PLA polymeric micelles firstly interacted with cell membrane using atomic force microscopy (AFM) and then released their core-loaded agents into the cell membrane by fluorescence resonance energy transfer (FRET). The released agents were internalized into the cells via lipid raft/caveolae-mediated endocytosis using total internal reflection fluorescence microscopy (TIRFM) and endocytic inhibitors. Further studies revealed that paclitaxel (PTX)-loaded PEG-b-PLA micelles (M-PTX) increased the cellular accumulation of PTX in PTX-resistant human ovarian cell line A2780/T which resulted in more apoptosis as measured by flow cytometry and the cleavage of poly (ADP-ribose) polymerase (PARP) compared with free PTX. PEG-b-PLA micelles inhibited P-glycoprotein (Pgp) function and Pgp ATPase activity but had no effect on Pgp protein expression. The membrane microenvironment studies showed that PEG-b-PLA micelles induced cell membrane depolarization and enhanced membrane microviscosity. These results suggested that PEG-b-PLA micelles might inhibit Pgp function to reverse multidrug resistance (MDR) via interaction with cell membrane to affect the membrane microenvironment. This study provides a foundation for understanding the mechanism of reversing MDR by nanoparticles better and designing more effective nano drug carriers.

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  1. Batrakova, 2001, Mechanism of pluronic effect on P-glycoprotein efflux system in blood-brain barrier: contributions of energy depletion and membrane fluidization, J Pharmacol Exp Ther, 299, 483, 10.1016/S0022-3565(24)29254-5 · DOI

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Metadata

Authors
Xiao, L., Xiong, X., Sun, X., Zhu, Y., Yang, H., Chen, H., Gan, L., Xu, H., & Yang, X.
Affiliations
Huazhong University of Science and Technology (CN)
Corresponding author
  • Gan, Lu
  • Yang, Xiangliang
ORCID
Venue
Biomaterials
Publisher
Elsevier BV
Published
2011-08
Volume
32
Issue
22
Pages
5148-5157
ISSN
0142-9612 (ISSN-L)
DOI
10.1016/j.biomaterials.2011.03.071
OpenAlex
W1984677400
Cited by
169
References
37
Citations by year
2025: 7 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 12 · 2019: 9 · 2018: 13 · 2017: 16 · 2016: 17 · 2015: 15 · 2014: 22 · 2013: 19 · 2012: 15
FWCI
7.74
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (30873121)
  • National Key Research and Development Program of China (2007CB935800, 2010CB934000)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
multidrug resistance reversal, P-glycoprotein inhibition, paclitaxel, cellular uptake, endocytosis, caveolae, lipid rafts, membrane microenvironment, membrane depolarization, membrane microviscosity, apoptosis, PARP cleavage, ovarian cancer cells, nano-drug delivery
MeSH terms
Antineoplastic Agents, Phytogenic, Cell Membrane, Drug Carriers, Endocytosis, Humans, Lactates, Materials Testing, Micelles, Particle Size, Polyethylene Glycols, Polymers, Apoptosis, Paclitaxel, Drug Resistance, Multiple, Microscopy, Atomic Force, ATP Binding Cassette Transporter, Subfamily B, Member 1, Fluorescence Resonance Energy Transfer, Cell Line, Tumor

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