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Journal article
Enhanced Prostate-specific Membrane Antigen Targeting by Precision Control of DNA Scaffolded Nanoparticle Ligand Presentation
ACS nano, v 18(26), pp 16674-16683
02 Jul 2024
PMID: 38907991
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects. The design of actively targeted nanoparticles requires the grafting of a ligand that specifically binds to a highly expressed receptor on the surface of the targeted cell population. Optimizing the interactions between the targeting ligand and the receptor can maximize the cellular uptake of the nanoparticles and subsequently improve their activity. Here, we evaluated how the density and presentation of the targeting ligands dictate the cellular uptake of nanoparticles. To do so, we used a DNA-scaffolded PLGA nanoparticle system to achieve efficient and tunable ligand conjugation. A prostate-specific membrane antigen (PSMA) expressing a prostate cancer cell line was used as a model. The density and presentation of PSMA targeting ligand ACUPA were precisely tuned on the DNA-scaffolded nanoparticle surface, and their impact on cellular uptake was evaluated. It was found that matching the ligand density with the cell receptor density achieved the maximum cellular uptake and specificity. Furthermore, DNA hybridization-mediated targeting chain rigidity of the DNA-scaffolded nanoparticle offered ∼3 times higher cellular uptake compared to the ACUPA-terminated PLGA nanoparticle. Our findings also indicated a ∼ 3.7-fold reduction in the cellular uptake for the DNA hybridization of the non-targeting chain. We showed that nanoparticle uptake is energy-dependent and follows a clathrin-mediated pathway. Finally, we validated the preferential tumor targeting of the nanoparticles in a bilateral tumor xenograft model. Our results provide a rational guideline for designing actively targeted nanoparticles and highlight the application of DNA-scaffolded nanoparticles as an efficient active targeting platform.
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Details
- Title
- Enhanced Prostate-specific Membrane Antigen Targeting by Precision Control of DNA Scaffolded Nanoparticle Ligand Presentation
- Creators
- Deblin Jana - Brown UniversityZhiyuan Han - University of California, San FranciscoXiao Huang - Drexel UniversityAnju Wadhwa - University of California, San FranciscoAthira Raveendran - University of California, San FranciscoKareem Ebeid - Brown UniversityNiranjan Meher - University of California, San FranciscoRobert R Flavell - University of California, San FranciscoTejal Desai (Corresponding Author) - University of California, San Francisco
- Publication Details
- ACS nano, v 18(26), pp 16674-16683
- Publisher
- ACS Publications
- Grant note
- P30 CA082103 / NCI NIH HHS R01 AI161829 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001261397200001
- Scopus ID
- 2-s2.0-85196835419
- Other Identifier
- 991022130635404721
UN Sustainable Development Goals (SDGs)
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Chemistry, Physical
- Materials Science, Multidisciplinary
- Nanoscience & Nanotechnology