Journal
BIOMATERIALS
Volume 35, Issue 30, Pages 8467-8478Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.06.032
Keywords
PEGylated NP; Cell membrane; Particle internalization; Surface grafting; Drug delivery
Funding
- National Science Foundation (NSF)
- Ryan Fellowship
- Royal E. Cabell Terminal Year Fellowship at Northwestern University
- Office of Science of the U.S. Department of Energy [DE-AC02-06CH11357]
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1130948] Funding Source: National Science Foundation
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Nanoparticles (NPs) are in use to efficiently deliver drug molecules into diseased cells. The surfaces of NPs are usually grafted with polyethylene glycol (PEG) polymers, during so-called PEGylation, to improve water solubility, avoid aggregation, and prevent opsonization during blood circulation. The interplay between grafting density sigma(p) and grafted PEG polymerization degree N makes cellular uptake of PEGylated NPs distinct from that of bare NPs. To understand the role played by grafted PEG polymers, we study the endocytosis of 8 nm sized PEGylated NPs with different sigma(p) and N through large scale dissipative particle dynamics (DPD) simulations. The free energy change F-polymer of grafted PEG polymers, before and after endocytosis, is identified to have an effect which is comparable to, or even larger than, the bending energy of the membrane during endocytosis. Based on self-consistent field theory F-polymer is found to be dependent on both sigma(p) and N. By incorporating F-polymer the critical ligand-receptor binding strength for PEGylated NPs to be internalized can be correctly predicted by a simple analytical equation. Without considering F-polymer, it turns out impossible to predict whether the PEGylated NPs will be delivered into the diseased cells. These simulation results and theoretical analysis not only provide new insights into the endocytosis process of PEGylated NPs, but also shed light on the underlying physical mechanisms, which can be utilized for designing efficient PEGylated NP-based therapeutic carriers with improved cellular targeting and uptake. (C) 2014 The Authors. Published by Elsevier Ltd.
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