Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/99346 https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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| author | Hanewich-Hollatz, Mikhail H. Gao, Weiwei Karim, Fawziya Karnik, Rohit Farokhzad, Omid C. Valencia, Pedro Miguel Langer, Robert S |
| author2 | MIT-Harvard Center for Cancer Nanotechnology Excellence |
| author_facet | MIT-Harvard Center for Cancer Nanotechnology Excellence Hanewich-Hollatz, Mikhail H. Gao, Weiwei Karim, Fawziya Karnik, Rohit Farokhzad, Omid C. Valencia, Pedro Miguel Langer, Robert S |
| author_sort | Hanewich-Hollatz, Mikhail H. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:35:38Z |
| format | Article |
| id | mit-1721.1/99346 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:35:38Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/993462022-09-27T20:35:01Z Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles Hanewich-Hollatz, Mikhail H. Gao, Weiwei Karim, Fawziya Karnik, Rohit Farokhzad, Omid C. Valencia, Pedro Miguel Langer, Robert S 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 Valencia, Pedro M. Gao, Weiwei Karim, Fawziya Langer, Robert Karnik, Rohit Farokhzad, Omid C. 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 2015-10-15T17:37:40Z 2015-10-15T17:37:40Z 2011-06 2011-04 Article http://purl.org/eprint/type/JournalArticle 01429612 1878-5905 http://hdl.handle.net/1721.1/99346 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. https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1016/j.biomaterials.2011.04.078 Biomaterials Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Hanewich-Hollatz, Mikhail H. Gao, Weiwei Karim, Fawziya Karnik, Rohit Farokhzad, Omid C. Valencia, Pedro Miguel Langer, Robert S Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title | Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title_full | Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title_fullStr | Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title_full_unstemmed | Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title_short | Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles |
| title_sort | effects of ligands with different water solubilities on self assembly and properties of targeted nanoparticles |
| url | http://hdl.handle.net/1721.1/99346 https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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