Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.
Sensitive and quantitative nucleic acid testing from complex biological samples is now an important component of clinical diagnostics. Whereas nucleic acid amplification represents the gold standard, its utility in resource-limited and point-of-care settings can be problematic due to assay interferants, assay time, engineering constraints, and costs associated with both wetware and hardware. In contrast, amplification-free nucleic acid testing can circumvent these limitations by enabling direct target hybridization within complex sample matrices. In this work, we grew random copolymer brushes from the surface of silica-coated magnetic nanoparticles using azide-modified and hydroxyl oligo ethylene glycol methacrylate (OEGMA) monomers. The azide-functionalized polymer brush was first conjugated, via copper-catalyzed azide/alkyne cycloaddition (CuAAC), with herpes simplex virus (HSV)-specific oligonucleotides and then with alkyne-substituted polyethylene glycol to eliminate all residual azide groups. Our methodology enabled control over brush thickness and probe density and enabled multiple consecutive coupling reactions on the particle grafted brush. Brush- and probe-modified particles were then combined in a 20 min hybridization with fluorescent polystyrene nanoparticles modified with HSV-specific reporter probes. Following magnetic capture and washing, the particles were analyzed with an aggregate fluorescence measurement, which yielded a limit of detection of 6 pM in buffer and 60 pM in 50% fetal bovine serum. Adoption of brush- and probe-modified particles into a particle counting assay will result in the development of diagnostic assays with significant improvements in sensitivity.
Timed-released disassembly of nanoparticles without a remote trigger or environmental cues is demonstrated in this work. The reversible addition-fragmentation chain transfer (RAFT) polymerization allowed the fine-tuning of the chemical composition in the diblock copolymers, in which the first block consisted of a hydrophilic monomer (DMA) and the second random block consisted of three different monomers: (a) the thermoresponsive NIPAM, (b) the self-catalyzed hydrolyzable DMAEA, and (c) the hydrophobic BA. These diblock copolymers were solubilized in water below the lower critical solution temperature (LCST) of the thermoresponsive second block, and heated to 37 °C (i.e., >LCST) to form small micelle nanoparticles with a narrow particle size distribution. As DMAEA hydrolyzed to acrylic acid groups, the LCST of the diblock increased, and the time at the start of micelle disassembly (t(start)) corresponded to the point where the LCST was equal to the solution temperature (i.e., 37 °C). The high water content in the PNIPAM core allowed an even degradation of the core over time. The copolymer composition allowed fine control over t(start), as this time was linearly dependent upon the BA units in the second block. These nanoparticles could also be designed to be stable (i.e., not disassemble) over a wide pH range or disassemble below a pH of 7.3. Additionally, the time from the start of disassembly to full unimer formation (t(degrade)) could be controlled by the amount of DMAEA units in the second block. A longer t(degrade) (~5.5 h) was found when the number of DMAEA units was 42 compared to t(degrade) of 1.1 h for 25 units. The nanoparticles designed in this work, through fine control of the polymer chemical composition, have the potential for drug delivery purposes for timed-release of drugs and prodrugs and other wide-ranging applications where timed-release would be beneficial.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.