Small interfering RNA-loaded chitosan hydrochloride/carboxymethyl chitosan nanoparticles for ultrasound-triggered release to hamper colorectal cancer growth in vitro

Colorectal Cancer
01/07/2020

Yan L, et al. Int J Biol Macromol 2020.

ABSTRACT

Development of nontoxic, targetable and potent small interfering RNAs (siRNA) delivery systems remains a predominant challenge for clinical application of siRNA therapy. The nanoparticles of carboxymethyl chitosan (CMC) and labeled fluorescein isothiocyanate (FITC)-chitosan hydrochloride (CHC) were fabricated as carriers for ultrasound-triggered drug delivery to treat colon cancer. The results showed the (FITC-CHC)-CMC nanoparticles could effectively encapsulate anti-β-catenin siRNA through


ionic gelation self-assembly to improve the stability of siRNA. The cumulative release ratio of siRNA from crosslinked (FITC-CHC)-CMC nanoparticles was merely 11.08% in pH 2.2 solution within 120 min, whereas about 70.07% of the loaded siRNA was released within 120 min in pH 5.5 solution after an 8-min ultrasonic treatment. It indicated that the (FITC-CHC)-CMC based pH-sensitive delivery system could fulfill a controlled release of siRNA through responding to external stimulus (ultrasound) under favorable pH condition. Fluorescence microscopy measurements clearly visualized the entry of fluorescently-labeled siRNA into HT-29 cells. Following the transfection of anti-β-catenin siRNA for 48 h, the β-catenin protein expression of the colon cancer cells was reduced to about 40.10%, indicating effective reduction of the protein that promotes colon cancer proliferation. Our results demonstrated that the siRNA-(FITC-CHC)-CMC delivery system hold substantial potential for RNAi therapeutical applications in diseased cells.