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Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles
Open accessAbstract
Understanding the interaction of nanoparticles (NPs) with the cell membrane and their trafficking through cells is imperative to fully explore the use of NPs for efficient intracellular delivery of therapeutics. Here, we report a novel method of measuring the force of NP-cell membrane interactions using atomic force microscopy (AFM). Poly(D,L-lactide-co-glycolide) (PLGA) NPs functionalized with poly-L-lysine were used as a model system to demonstrate that this force determines the adhesive interaction of NPs with the cell membrane and in turn the extent of cellular uptake of NPs, and hence that of the encapsulated therapeutic. Cellular uptake of NPs was monitored using AFM imaging and the dynamics of their intracellular distribution was quantified using confocal microscopy. Results demonstrated that the functionalized NPs have a five-fold greater force of adhesion with the cell membrane and the time-lapse AFM images show their rapid internalization than unmodified NPs. The intracellular trafficking study showed that the functionalized NPs escape more rapidly and efficiently from late endosomes than unmodified NPs and result in 10-fold higher intracellular delivery of the encapsulated model protein. The findings described herein enhance our basic understanding of the NP-cell membrane interaction on the basis of physical phenomena that could have wider applications in developing efficient nanocarrier systems for intracellular delivery of therapeutics.
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“For example, Kohori et al. [160] evaluated the structural modifications of thermo-responsive block copolymer micelles after drying at 4 • C and 40 • C, pointing out the presence of rounded-shape individually dispersed micelles at 4 • C in contrast with aggregated systems, often retaining their spherical shape, at the higher temperature.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [160]
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Metadata
- Authors
- Vasir, J. K., & Labhasetwar, V.
- Affiliations
- Cleveland Clinic (US)
- ORCID
- Labhasetwar, Vinod
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 29
- Issue
- 31
- Pages
- 4244-4252
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2570224
- OpenAlex
- W2041164141
- Cited by
- 268
- References
- 37
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 20 · 2019: 16 · 2018: 20 · 2017: 17 · 2016: 23 · 2015: 17 · 2014: 21 · 2013: 19 · 2012: 17
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering
- American Heart Association (0515489Z)
- National Institutes of Health
- 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 › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- nanoparticle-cell membrane interaction, adhesion force, intracellular trafficking, PLGA nanoparticles, cellular uptake, endosomal escape, late endosomes, intracellular delivery, nanocarriers, atomic force microscopy
- MeSH terms
- Biological Transport, Biomechanical Phenomena, Cell Membrane, Cell Survival, Cytoplasm, Horseradish Peroxidase, Microscopy, Atomic Force, Intracellular Space, Nanoparticles
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