Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs
Open accessAbstract
Co-delivery of hydrophilic siRNA and hydrophobic drugs is one of the major challenges for nanomaterial-based medicine. Here, we present a simple but multifunctional micellar platform constructed by a matrix metalloproteinase 2 (MMP2)-sensitive copolymer (PEG-pp-PEI-PE) via self-assembly for tumor-targeted siRNA and drug co-delivery. The micellar nanocarrier possesses several key features for siRNA and drug delivery, including (i) excellent stability; (ii) efficient siRNA condensation by PEI; (iii) hydrophobic drug solubilization in the lipid "core"; (iv) passive tumor targeting via the enhanced permeability and retention (EPR) effect; (v) tumor targeting triggered by the up-regulated tumoral MMP2; and (vi) enhanced cell internalization after MMP2-activated exposure of the previously hidden PEI. These cooperative functions ensure the improved tumor targetability, enhanced tumor cell internalization, and synergistic antitumor activity of co-loaded siRNA and drug.
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Polymeric nanomicelles (PNMs) are prepared from amphiphilic polymers, range in size from 1 to 200 nm, and contain an inner hydrophobic core and an outer hydrophilic shell; the outer shell controls pharmacokinetic properties and the inner core is responsible for drug entrapment, stability, and drug-release characteristics.
“Another category is polymeric nanomicelles (PNMs) prepared from amphiphilic polymers; they have a size that ranges from 1 to 200 nm. This type of nanoparticles contains two functional portions, an “inner core” and an “outer shell”.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [42]
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- Authors
- Zhu, L., Perche, F., Wang, T., & Torchilin, V. P.
- Affiliations
- Texas A&M Health Science Center (US)
- Northeastern University (US)
- Corresponding author
- Torchilin, Vladimir P.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 35
- Issue
- 13
- Pages
- 4213-4222
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3981970
- OpenAlex
- W2060170811
- Cited by
- 220
- References
- 26
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 8 · 2023: 12 · 2022: 16 · 2021: 11 · 2020: 19 · 2019: 27 · 2018: 27 · 2017: 27 · 2016: 17 · 2015: 30 · 2014: 6
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- NIH (1R01CA121838, U54CA151881)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- MMP-2, polymeric micelles, siRNA delivery, hydrophobic drug delivery, co-delivery, polyethyleneimine, tumor targeting, enhanced permeability and retention effect, cellular internalization, synergistic antitumor effect
- MeSH terms
- Humans, Micelles, Phosphatidylethanolamines, Polyethylene Glycols, Polymers, Drug Delivery Systems, Matrix Metalloproteinase 2, RNA, Small Interfering, Cell Line, Tumor, Hydrophobic and Hydrophilic Interactions
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