Presentation Type
Oral Presentation
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Multimodality platforms integrating targeting, therapeutic and diagnostic modalities are gaining attention in the area of smart nanomedicines for cancers. However, their multi-step synthesis strategies are the major bottleneck for large-scale production with high reproducibility. Isocyanide-based multi-component reactions (IMCRs) have become popular in modern chemistry and have offered effective access to highly diverse and complex final products in a single step. Herein, isocyanide-based 4-component (4CRs) UGI reaction is optimized on virus-like particles (VLPs) to develop multimodal nanoplatforms more efficiently.
Methods: In this work, biocatalytic P22CYP nanoreactors were multifunctionalized with: (i) enzyme Glucose Oxidase (GOx) to obtain a cascade enzymatic activity for prodrug transformation, (ii) a photosensitizer, Indocyanine green (ICG) for NIR activated photodynamic and photothermal therapy, and (iii) a targeting ligand, 2-Deoxy-d-glucose (2DG). The VLPs were exposed to UGI reaction at room temperature and variable ionic strength, reagent concentrations, and times. They were later characterized through enzymatic activity, photosensitizer quantification and electron microscopy.
Results: There was no significant difference in the extent of surface functionalization of GOx and ICG when the concentration of UGI reagents, t-butylisocyanide and formaldehyde were varied. TEM analysis revealed the preserved integrity of VLP under all reaction conditions suggesting no significant affect of UGI reaction on proteinaceous nanostructure. The functionalized ICG generated reactive oxygen species and raised the temperature of medium up to 3.6°C after excitation at 808 nm. The synergy of photothermal and photodynamic property on the glucose mediated prodrug transformation was also evaluated by HPLC and displayed higher transformation rates. The functionalization of 2-DG could not be characterized in this work, therefore, future work will focus on the identification of targeting ability of nanoreactors by cell internalization assay.
Conclusions: Our preliminary analysis shows that multimodal P22CYP-GOx-IcG-2DG could be a potential candidate for quadruple combination therapy and NIR imaging of cancer. These results highlight the potential of 4CR UGI reaction for one-step multifunctionalization of protein based nanoparticles under ambient conditions for the development of cancer therapy nanoplatforms.
Academic/Professional Position
Graduate Student
Recommended Citation
Dorado Baeza, Andrea; Sengar, Prakhar; Vázquez-Duhalt, Rafael; and Chauhan, Kanchan, "Optimization and characterization of one-step multi-functionalization of virus-like particles for multimodality nanoplatforms" (2024). Research Symposium. 40.
https://scholarworks.utrgv.edu/somrs/2024/talks/40
Included in
Optimization and characterization of one-step multi-functionalization of virus-like particles for multimodality nanoplatforms
Background: Multimodality platforms integrating targeting, therapeutic and diagnostic modalities are gaining attention in the area of smart nanomedicines for cancers. However, their multi-step synthesis strategies are the major bottleneck for large-scale production with high reproducibility. Isocyanide-based multi-component reactions (IMCRs) have become popular in modern chemistry and have offered effective access to highly diverse and complex final products in a single step. Herein, isocyanide-based 4-component (4CRs) UGI reaction is optimized on virus-like particles (VLPs) to develop multimodal nanoplatforms more efficiently.
Methods: In this work, biocatalytic P22CYP nanoreactors were multifunctionalized with: (i) enzyme Glucose Oxidase (GOx) to obtain a cascade enzymatic activity for prodrug transformation, (ii) a photosensitizer, Indocyanine green (ICG) for NIR activated photodynamic and photothermal therapy, and (iii) a targeting ligand, 2-Deoxy-d-glucose (2DG). The VLPs were exposed to UGI reaction at room temperature and variable ionic strength, reagent concentrations, and times. They were later characterized through enzymatic activity, photosensitizer quantification and electron microscopy.
Results: There was no significant difference in the extent of surface functionalization of GOx and ICG when the concentration of UGI reagents, t-butylisocyanide and formaldehyde were varied. TEM analysis revealed the preserved integrity of VLP under all reaction conditions suggesting no significant affect of UGI reaction on proteinaceous nanostructure. The functionalized ICG generated reactive oxygen species and raised the temperature of medium up to 3.6°C after excitation at 808 nm. The synergy of photothermal and photodynamic property on the glucose mediated prodrug transformation was also evaluated by HPLC and displayed higher transformation rates. The functionalization of 2-DG could not be characterized in this work, therefore, future work will focus on the identification of targeting ability of nanoreactors by cell internalization assay.
Conclusions: Our preliminary analysis shows that multimodal P22CYP-GOx-IcG-2DG could be a potential candidate for quadruple combination therapy and NIR imaging of cancer. These results highlight the potential of 4CR UGI reaction for one-step multifunctionalization of protein based nanoparticles under ambient conditions for the development of cancer therapy nanoplatforms.