Unknown

Dataset Information

0

Anionic Polymer and Quantum Dot Excipients to Facilitate siRNA Release and Self-Reporting of Disassembly in Stimuli-Responsive Nanocarrier Formulations.


ABSTRACT: The incorporation of anionic excipients into polyplexes is a promising strategy for modulating siRNA binding versus release and integrating diagnostic capabilities; however, specific design criteria and structure-function relationships are needed to facilitate the development of nanocarrier-based theranostics. Herein, we incorporated poly(acrylic acid) (PAA) and quantum dot (QD) excipients into photolabile siRNA polyplexes to increase gene silencing efficiencies by up to 100% and enable self-reporting of nanocarrier disassembly. Our systematic approach identified the functional relationships between gene silencing and key parameters such as excipient loading fractions and molecular weights that facilitated the establishment of design rules for optimization of nanocarrier efficacy. For example, we found that PAA molecular weights ?10-20× greater than that of the coencapsulated siRNA exhibited the most efficient release and silencing. Furthermore, siRNA release assays and RNAi modeling allowed us to generate a PAA "heat map" that predicted gene silencing a priori as a function of PAA molecular weight and loading fraction. QDs further promoted selective siRNA release and provided visual as well as Förster resonance energy transfer (FRET)-based monitoring of the dynamic changes in nanostructure in situ. Moreover, even with the addition of anionic components, our formulations exhibited substantially improved stability and shelf life relative to typical formulations, with complete stability after a week of storage and full activity in the presence of serum. Taken together, this study enabled synergistic improvements in siRNA release and diagnostic capabilities, along with the development of mechanistic insights that are critical for advancing the translation of nucleic acid theranostics into the clinic.

SUBMITTER: Greco CT 

PROVIDER: S-EPMC5672795 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5317101 | BioStudies
2011-01-01 | S-EPMC3185110 | BioStudies
1000-01-01 | S-EPMC6023847 | BioStudies
2010-01-01 | S-EPMC2791204 | BioStudies
1000-01-01 | S-EPMC4050376 | BioStudies
2009-01-01 | S-EPMC2754713 | BioStudies
1000-01-01 | S-EPMC4894661 | BioStudies
2017-01-01 | S-EPMC5919184 | BioStudies
2019-01-01 | S-EPMC6723413 | BioStudies
1000-01-01 | S-EPMC5057072 | BioStudies