Cited by 91RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryDendrimers and Hyperbranched Polymers

Poly(2-ethyl-2-oxazoline)-PLA-g-PEI amphiphilic triblock micelles for co-delivery of minicircle DNA and chemotherapeutics

Gaspar, Vítor M., Gonçalves, Cristine, de Melo-Diogo, Duarte, Costa, Elisabete C., Queiroz, João A., Pichon, Chantal, Sousa, Fani, Correia, Ilídio J.·2014·Journal of Controlled Release

Abstract

The design of nanocarriers for the delivery of drugs and nucleic-acids remains a very challenging goal due to their physicochemical differences. In addition, the reported accelerated clearance and immune response of pegylated nanomedicines highlight the necessity to develop carriers using new materials. Herein, we describe the synthesis of amphiphilic triblock poly(2-ethyl-2-oxazoline)-PLA-g-PEI (PEOz-PLA-g-PEI) micelles for the delivery of minicircle DNA (mcDNA) vectors. In this copolymer the generally used PEG moieties are replaced by the biocompatible PEOz polymer backbone that assembles the hydrophilic shell. The obtained results show that amphiphilic micelles have low critical micellar concentration, are hemocompatible and exhibit stability upon incubation in serum. The uptake in MCF-7 cells was efficient and the nanocarriers achieved 2.7 fold higher expression than control particles. Moreover, mcDNA-loaded micelleplexes penetrated into 3D multicellular spheroids and promoted widespread gene expression. Additionally, to prove the concept of co-delivery, mcDNA and doxorubicin (Dox) were simultaneously encapsulated in PEOz-PLA-g-PEI carriers, with high efficiency. Dox-mcDNA micelleplexes exhibited extensive cellular uptake and demonstrated anti-tumoral activity. These findings led us to conclude that this system has a potential not only for the delivery of novel mcDNA vectors, but also for the co-delivery of drug-mcDNA combinations without PEG functionalization.

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Crossref · 10.1016/j.jconrel.2014.06.040

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Authors
Gaspar, V. M., Gonçalves, C., de Melo-Diogo, D., Costa, E. C., Queiroz, J. A., Pichon, C., Sousa, F., & Correia, I. J.
Affiliations
  • University of Beira Interior (PT)
  • Université d'Orléans (FR)
Corresponding author
Correia, Ilídio J.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2014-09
Volume
189
Pages
90-104
ISSN
0168-3659 (ISSN-L)
OpenAlex
W2049971305
Cited by
91
References
58
Citations by year
2026: 1 · 2025: 7 · 2024: 2 · 2023: 4 · 2021: 2 · 2020: 4 · 2019: 10 · 2018: 16 · 2017: 12 · 2016: 12 · 2015: 17 · 2014: 3
FWCI
6.02
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
Funders
Portuguese Foundation for Science and Technology (PTDC/EBB-BIO/114320/2009, PEst-C/SAU/UI0709/2011)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
poly(2-ethyl-2-oxazoline), polylactic acid, poly(ethyleneimine), amphiphilic triblock copolymers, micelles, DNA minicircles, gene delivery, doxorubicin, co-delivery, hemocompatibility, multicellular spheroids, MCF-7 cells, anticancer activity, critical micelle concentration
MeSH terms
Animals, Antibiotics, Antineoplastic, Breast Neoplasms, DNA, Circular, Doxorubicin, Drug Carriers, Erythrocytes, Female, Fibroblasts, Hemolysis, Humans, Mice, Inbred BALB C, Micelles, Polyamines, Polyesters, Polyethyleneimine, Polymers, Rats, Wistar, Spheroids, Cellular, Lactic Acid, Cell Line, Tumor, Green Fluorescent Proteins, MCF-7 Cells

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