dc.contributor.advisor | Rivera, Jose M. | |
dc.contributor.author | Acosta-Santiago, Maxier | |
dc.date.accessioned | 2021-09-30T18:47:29Z | |
dc.date.available | 2021-09-30T18:47:29Z | |
dc.date.issued | 2021-01-14 | |
dc.identifier.uri | https://hdl.handle.net/11721/2586 | |
dc.description.abstract | Colloidal particles ranging from the nano to the microscale show great promise in the delivery and enhancement of therapeutic agents. The formulation of many of these particles usually includes crosslinkers, non-biocompatible solvents, or lengthy procedures that are not cost-effective. We have developed particles termed Supramolecular Hacky Sacks (SHS) via thermo-responsive Supramolecular G-quadruplexes (SGQs) with lower critical solution temperature (LCST). SGQs are formed by the self-assembly of G-derivatives. SHS particles have served as HIV-1 vaccine adjuvants and encapsulate small molecules, proteins, and plasmid DNA. Here we are showing multiple strategies taken to expand the SHS particles’ properties with the ultimate goal of making them suitable for more biocompatible environments. In chapter 2, we showcase the use of potassium thiocyanate to enhance the solubility of various G-derivatives, which enables modulation of the LCST phenomenon of the corresponding SGQ structures. We also highlight the role of such salt in the corresponding upper critical solution temperature (UCST). In chapter 3, we demonstrate the use of the Thiol-Michael reaction between a G-derivative having an α,β-unsaturated enone with biothiols like cysteine and glutathione as a viable strategy to modulate the formation of the SGQs and the corresponding SHS particles. Furthermore, the addition of biothiols to SHS triggered the controlled release of encapsulated Rhodamine B. This provided proof of concept for longer term drug-delivery applications. Chapter 4 demonstrates the use of an alternative strategy to achieve an analogous responsive behavior towards cysteine. In chapter 4 we explored the reaction of a formyl-containing G-derivative with cysteine to form a thiazolidinecarboxylate moiety. The thiazolidine-carboxylate enhanced hydrophilicity and greater steric bulk. The enhanced properties induced the disassembly of the SHS particles. Encapsulation and release studies using Rhodamine B showed similar behavior described in chapter 3, but with different kinetic and thermodynamic parameters. We expect these relatively simple strategies to enable the development of sophisticated supramolecular based particles for biomedical applications. | en_US |
dc.description.sponsorship | RISE Program (5R25GM061151) | en_US |
dc.language.iso | en_US | en_US |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
dc.subject | G-quadruplex | en_US |
dc.subject | Guanosine | en_US |
dc.subject | Hofmeister series | en_US |
dc.subject | LCST | en_US |
dc.subject | Thiol-responsive | en_US |
dc.subject | UCST | en_US |
dc.subject.lcsh | Confocal microscopy | en_US |
dc.subject.lcsh | Quadruplex nucleic acids | en_US |
dc.subject.lcsh | Self-assembly (Chemistry) | en_US |
dc.subject.lcsh | Supramolecular chemistry | en_US |
dc.title | Biologically relevant formulation and expansion of responsive properties of guanine based supramolecular particles. | en_US |
dc.type | Dissertation | en_US |
dc.rights.holder | © 2021 Maxier Acosta-Santiago | en_US |
dc.contributor.committee | Tinoco, Arthur D. | |
dc.contributor.committee | Bayro, Marvin | |
dc.contributor.committee | Carballeira, Nestor M. | |
dc.contributor.committee | Lopez-Mejias, Vilmari | |
dc.contributor.representative | Diaz-Vázquez, Liz M. | |
dc.contributor.campus | University of Puerto Rico, Río Piedras Campus | en_US |
dc.description.graduationSemester | Spring (2nd Semester) | en_US |
dc.description.graduationYear | 2021 | en_US |
thesis.degree.discipline | Chemistry | en_US |
thesis.degree.level | Ph.D. | en_US |