Home / Publications / Featured Publications / Tuning Selectivity of Dendron Micelles through Variations of the PEG Corona

Tuning Selectivity of Dendron Micelles through Variations of the PEG Corona

June 6, 2016

Cite this

Abstract

Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA-mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs.

Cited by

This article is cited by 13 publications

Dodd-O, J., Roy, A., Siddiqui, Z., Jafari, R., Coppola, F., Ramasamy, S., Kolloli, A., Kumar, D., Kaundal, S., Zhao, B., Kumar, R., Robang, A. S., Li, J., Azizogli, A. R., Pai, V., Acevedo-Jake, A., Heffernan, C., Lucas, A., McShan, A. C., Paravastu, A. K., … Kumar, V. (2024). Antiviral fibrils of self-assembled peptides with tunable compositions. Nature communications, 15(1), 1142. https://doi.org/10.1038/s41467-024-45193-3
Rawding, P. A., Bu, J., Wang, J., Kim, D. W., Drelich, A. J., Kim, Y., & Hong, S. (2022). Dendrimers for cancer immunotherapy: Avidity-based drug delivery vehicles for effective anti-tumor immune response. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 14(2), e1752. https://doi.org/10.1002/wnan.1752
Jeong, W. J., Bu, J., Jafari, R., Rehak, P., Kubiatowicz, L. J., Drelich, A. J., Owen, R. H., Nair, A., Rawding, P. A., Poellmann, M. J., Hopkins, C. M., Král, P., & Hong, S. (2022). Hierarchically Multivalent Peptide-Nanoparticle Architectures: A Systematic Approach to Engineer Surface Adhesion. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9(4), e2103098. https://doi.org/10.1002/advs.202103098
Skibba, M., Drelich, A., Poellmann, M., Hong, S., & Brasier, A. R. (2020). Nanoapproaches to Modifying Epigenetics of Epithelial Mesenchymal Transition for Treatment of Pulmonary Fibrosis. Frontiers in pharmacology, 11, 607689. https://doi.org/10.3389/fphar.2020.607689
Chakraborty, A., Lasola, J., Truong, N., & Pearson, R. M. (2020). Serum-Independent Nonviral Gene Delivery to Innate and Adaptive Immune Cells Using Immunoplexes. ACS applied bio materials, 3(9), 6263–6272. https://doi.org/10.1021/acsabm.0c00761
Yadav, S., Sharma, A. K., & Kumar, P. (2020). Nanoscale Self-Assembly for Therapeutic Delivery. Frontiers in bioengineering and biotechnology, 8, 127. https://doi.org/10.3389/fbioe.2020.00127
Sanchez-Cano, C., & Carril, M. (2020). Recent Developments in the Design of Non-Biofouling Coatings for Nanoparticles and Surfaces. International journal of molecular sciences, 21(3), 1007. https://doi.org/10.3390/ijms21031007
Sen, S., Vuković, L., & Král, P. (2019). Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils. Scientific reports, 9(1), 17804. https://doi.org/10.1038/s41598-019-52594-8
Skoumal, M., Woodward, K. B., Zhao, H., Wang, F., Yolcu, E. S., Pearson, R. M., Hughes, K. R., García, A. J., Shea, L. D., & Shirwan, H. (2019). Localized immune tolerance from FasL-functionalized PLG scaffolds. Biomaterials, 192, 271–281. https://doi.org/10.1016/j.biomaterials.2018.11.015
Vieira Gonzaga, R., da Silva Santos, S., da Silva, J. V., Campos Prieto, D., Feliciano Savino, D., Giarolla, J., & Igne Ferreira, E. (2018). Targeting Groups Employed in Selective Dendrons and Dendrimers. Pharmaceutics, 10(4), 219. https://doi.org/10.3390/pharmaceutics10040219
Hsu, H. J., Han, Y., Cheong, M., Král, P., & Hong, S. (2018). Dendritic PEG outer shells enhance serum stability of polymeric micelles. Nanomedicine : nanotechnology, biology, and medicine, 14(6), 1879–1889. https://doi.org/10.1016/j.nano.2018.05.010
Bolu, B. S., Sanyal, R., & Sanyal, A. (2018). Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates †. Molecules (Basel, Switzerland), 23(7), 1570. https://doi.org/10.3390/molecules23071570
Shaw, S. K., Liu, W., Brennan, S. P., de Lourdes Betancourt-Mendiola, M., & Smith, B. D. (2017). Non-Covalent Assembly Method that Simultaneously Endows a Liposome Surface with Targeting Ligands, Protective PEG Chains, and Deep-Red Fluorescence Reporter Groups. Chemistry (Weinheim an der Bergstrasse, Germany), 23(51), 12646–12654. https://doi.org/10.1002/chem.201702649

Tuning Selectivity of Dendron Micelles through Variations of the PEG Corona

Abstract

Published

Cited by