Anionic polymer and quantum dot excipients to facilitate siRNA release and self-reporting of disassembly in stimuli-responsive nanocarrier formulations.

Anionic polymer and quantum dot excipients to facilitate siRNA release and self-reporting of disassembly in stimuli-responsive nanocarrier formulations. Biomacromolecules. 2017 Apr 25;: Authors: Greco CT, Andrechak JC, Epps Iii TH, Sullivan MO Abstract The incorporation of anionic excipients into polyplexes is a promising strategy for modulating siRNA binding vs. 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 enabled the establishment of design rules for optimization of nanocarrier efficacy. For example, we found that PAA molecular weights ~10-20 times greater than that of the co-encapsulated 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...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research