1 research outputs found
Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P‑gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer
Prerelease of RNA
molecules than chemotherapeutic drugs with a sufficient interval is
a vital prerequisite for RNA/drug co-delivery strategy to overcome
multidrug resistance (MDR) of cancer cells, but how to precisely control
their release at different time points is still a grand challenge
up to now. This study aims to on-demand remotely manipulate RNA and
drug release in real time through single delivery system to sequentially
play their respective roles for optimizing and enhancing their synergistic
antitumor effects. To this end, a photoresponsive mesoporous silica
nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein
(P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin
(DOX), by which the orthogonal and sequential release of shRNA and
DOX can be achieved using an external light. In our design, the cationic
poly[2-(<i>N</i>,<i>N</i>-dimethylaminoethyl)methacrylate]
is introduced onto the PMSN surface through a light-sensitive coumarin
ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable <i>o</i>-nitrobenzyl ester derivative-caged DOX is loaded into
the inner pores of the PMSN. The PMSN is found to be effectively internalized
by MDR cancer cells, and the release of the shRNA and DOX is demonstrated
to be independently regulated by 405 and 365 nm light irradiations
due to selectively cleaved coumarin and <i>o</i>-nitrobenzyl
ester, resulting in enhanced drug retention, and finally bring out
optimized and significantly improved chemotherapeutic effects both
in vitro and in vivo for MDR cancer treatment, which might hold extensive
application prospects in MDR cancer treatment in future