Cited by 355Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryAdvanced Drug Delivery Systems

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pH-sensitive poly (histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery

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Wu, Hong, Zhu, Lin, Torchilin, Vladimir P.·2013·Biomaterials

DOI 10.1016/j.biomaterials.2012.08.072PMC PMC3587181

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Abstract

To introduce pH sensitivity into the DSPE-PEG-based micellar system and achieve the quick intracellular drug release in response to the acidity in endosomes, a mixed polymeric micelle was developed based on three grafted copolymers, including 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000(DSPE-PEG(2000)), antinucleosome antibody (mAb 2C5)-modified DSPE-PEG(3400) (DSPE-PEG(3400)-2C5), and poly(ethylene glycol)-coupled poly(L-histidine) (PHIS-PEG(2000)). The structure of PHIS-PEG(2000) was confirmed by (1)H NMR spectroscopy. The mixed micelles with the diameter ranging from 110 to 135 nm were prepared using a dialysis method against pH 7.6 PBS. Paclitaxel (PCT) was used as a model drug, the encapsulation efficiency and loading content of PCT were 88% and 5%, respectively. The mixed micelles composed with 50 wt% of PHIS-PEG(2000) showed the desired pH-dependent drug release property with much faster drug release than micelles without PHIS-PEG(2000). At pH around 5.5, about 75-95% of the loaded drug was released within 2 h. The MTT assay showed PCT-loaded mixed micelles had higher cytotoxicity at pH 5.8 than that at pH 7.4. Further modification of the mixed micelles with anti-cancer nucleosome-specific monoclonal antibody 2C5 significantly increased their cellular uptake efficiency and cytotoxicity. Thus, the low pH in endosomes could trigger the PCT release from the pH-sensitive mixed micelles after 2C5-mediated endocytosis. The results of this study suggest that the mixed micelles (DSPE-PEG(2000)/DSPE-PEG(3400)-2C5/PHIS-PEG(2000)) could enhance the tumor cell-specific internalization and trigger the quick drug release, resulting in the improved anti-cancer efficacy.

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Authors: Wu, H., Zhu, L., & Torchilin, V. P.
Affiliations: Northeastern University (US)
Corresponding author: Torchilin, Vladimir P.
ORCID: Wu, Hong
Zhu, Lin
Torchilin, Vladimir P.
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2013-01
Volume: 34
Issue: 4
Pages: 1213-1222
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2012.08.072
PMC: PMC3587181
OpenAlex: W1979335059
Cited by: 355
References: 40
Citations by year: 2026: 11 · 2025: 14 · 2024: 11 · 2023: 13 · 2022: 27 · 2021: 25 · 2020: 26 · 2019: 33 · 2018: 30 · 2017: 45 · 2016: 37 · 2015: 40 · 2014: 31 · 2013: 12
FWCI: 10.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biomaterials (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (1R01CA121838)
National Natural Science Foundation of China (30970788)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: pH-responsive micelles, DSPE-PEG, mixed micelles, paclitaxel, cellular uptake, tumor cell internalization, cytosolic drug delivery, anticancer drug delivery
MeSH terms: Animals, Antineoplastic Agents, Phytogenic, Breast Neoplasms, Cytosol, Diffusion, Hydrogen-Ion Concentration, Micelles, Phosphatidylethanolamines, Polyethylene Glycols, Proteins, Paclitaxel, Cell Line, Tumor, Mice, Nanocapsules

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pH-sensitive poly (histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery

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