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Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles

Author(s)
Hanewich-Hollatz, Mikhail H.; Gao, Weiwei; Karim, Fawziya; Karnik, Rohit; Farokhzad, Omid C.; Valencia, Pedro Miguel; Langer, Robert S; ... Show more Show less
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Abstract
The engineering of drug-encapsulated targeted nanoparticles (NPs) has the potential to revolutionize drug therapy. A major challenge for the smooth translation of targeted NPs to the clinic has been developing methods for the prediction and optimization of the NP surface composition, especially when targeting ligands (TL) of different chemical properties are involved in the NP self-assembly process. Here we investigated the self-assembly and properties of two different targeted NPs decorated with two widely used TLs that have different water solubilities, and developed methods to characterize and optimize NP surface composition. We synthesized two different biofunctional polymers composed of poly(lactide-co-glycolide)-b-polyethyleneglycol-RGD (PLGA-PEG-RGD, high water solubility TL) and PLGA-PEG-Folate (low water solubility TL). Targeted NPs with different ligand densities were prepared by mixing TL-conjugated polymers with non-conjugated PLGA-PEG at different ratios through nanoprecipitation. The NP surface composition was quantified and the results revealed two distinct nanoparticle assembly behaviors: for the case of PLGA-PEG-RGD, nearly all RGD molecules conjugated to the polymer were found to be on the surface of the NPs. In contrast, only ~20% of the folate from PLGA-PEG-Folate was present on the NP surface while the rest remained presumably buried in the PLGA NP core due to hydrophobic interactions of PLGA and folate. Finally, in vitro phagocytosis and cell targeting of NPs were investigated, from which a window of NP formulations exhibiting minimum uptake by macrophages and maximum uptake by targeted cells was determined. These results underscore the impact that the ligand chemical properties have on the targeting capabilities of self-assembled targeted nanoparticles and provide an engineering strategy for improving their targeting specificity.
Date issued
2011-06
URI
http://hdl.handle.net/1721.1/99346
Department
MIT-Harvard Center for Cancer Nanotechnology Excellence; Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Biomaterials
Publisher
Elsevier
Citation
Valencia, Pedro M., Mikhail H. Hanewich-Hollatz, Weiwei Gao, Fawziya Karim, Robert Langer, Rohit Karnik, and Omid C. Farokhzad. “Effects of Ligands with Different Water Solubilities on Self-Assembly and Properties of Targeted Nanoparticles.” Biomaterials 32, no. 26 (September 2011): 6226–6233.
Version: Author's final manuscript
ISSN
01429612
1878-5905

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