1. Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles
- Author
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Pedro M. Valencia, Robert Langer, Omid C. Farokhzad, Weiwei Gao, Rohit Karnik, Fawziya Karim, Mikhail H. Hanewich-Hollatz, MIT-Harvard Center for Cancer Nanotechnology Excellence, Institute for Medical Engineering and 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, Valencia, Pedro M., Gao, Weiwei, Karim, Fawziya, Langer, Robert, Karnik, Rohit, and Farokhzad, Omid C.
- Subjects
Materials science ,Polymers ,Biophysics ,Nanoparticle ,Bioengineering ,macromolecular substances ,Conjugated system ,Article ,Cell Line ,Polyethylene Glycols ,Biomaterials ,Hydrophobic effect ,chemistry.chemical_compound ,Mice ,Folic Acid ,Polylactic Acid-Polyglycolic Acid Copolymer ,Organic chemistry ,Molecule ,Animals ,Humans ,Lactic Acid ,Solubility ,Ligand ,technology, industry, and agriculture ,Water ,Combinatorial chemistry ,PLGA ,chemistry ,Mechanics of Materials ,Ceramics and Composites ,Nanoparticles ,Self-assembly ,Hydrophobic and Hydrophilic Interactions ,Polyglycolic Acid - 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., Prostate Cancer Foundation (Award in Nanotherapeutics), National Cancer Institute (U.S.) (Center of Cancer Nanotechnology Excellence at MIT-Harvard U54-CA151884), National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology Award Contract HHSN268201000045C), National Science Foundation (U.S.). Graduate Research Fellowship
- Published
- 2011