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

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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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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: Xiao, Ling
Zhu, Yanhong
Yang, Hao
Chen, Huabing
Gan, Lu
Yang, Xiangliang
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
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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Role of cellular uptake in the reversal of multidrug resistance by PEG-b-PLA polymeric micelles

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