Treatment of brain diseases remains a challenge due to the difficulties of therapeutic agents' delivery to the brain. Specifically, the application of hydrophobic neuro-regenerative drugs was limited due to their poor bioavailability caused by insolubility and short half-life, and lack of effective targeting and controllable release. Herein, we presented our study on developing a novel 808nm near-infrared (NIR) responsive drug delivery vehicle, the core-shell superparamagnetic iron oxide-hollow gold nanoshell (SPIO@HGNS) functionalized with positively charged porous coordination cages (PCCs). The 808nm NIR light matches HGNS's surface plasmon resonance and has the excellent tissue penetration ability to reach the brain area. The ion-exchange resin (IER) mediated surface modification by (11-Mercaptoundecyl)-N, N, N-trimethylammonium bromide (MUTAB) tuned the overall surface charge from negative to positive, which enabled the encapsulation of anionic retinoic acid (RA).  The dose-dependent improvement of RA loading was revealed by zeta potential and NMR results. Higher drug loading efficiency was achieved comparing to pure HGNS or SPIO/Au nanoparticles. Uniform nanoparticle dispersity was also observed by TEM. The in vitro release of RA was performed under the stimulation of 808nm (100mW/cm<sup>2</sup>) NIR ultrafast LASER at an interval of 3 h with each time NIR-exposure of 10 min. The RA release kinetics was evaluated by measuring the absorbance of RA via UV-Vis. Results revealed that RA's higher release rate was triggered by the stimulation of NIR light, demonstrating the light-controllable drug release kinetics. The proposed SPIO@HGNS nanocarrier has the potential for controlled drug release in the targeted brain site because of the magnetic nature itself and the NIR-responsive drug release mechanism.

Porous coordination cages based stimuli-responsive nanocarriers for controlled drug release

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.