Photo-Triggered Delivery of siRNA and Paclitaxel into Breast Cancer Cells Using Catanionic Vesicles

Abstract

Localized drug delivery holds great promise as a means of circumventing traditional chemotherapy side effects associated with high toxicity and prolonged treatments. Nanosized carriers (i.e., with diameters <100 nm) can often accumulate in tumor cells, yet it remains a challenge to design such carriers that are at the same time durable (to survive delivery) and degradable (to release the payload once inside cells). In the present study, photoresponsive catanionic vesicles are utilized to codeliver Bcl-2 siRNA and paclitaxel into MDA-MB-231 human breast cancer cells. These vesicles, which form spontaneously upon simple mixing of an azobenzene-based cationic surfactant and a conventional anionic surfactant, disassociate into free surfactants upon UV illumination. This allows for phototriggered release of the coloaded therapeutics following cellular uptake, which is shown to enhance both cell death and protein suppression. Dynamic light scattering, zeta potential, small-angle neutron scattering, and fluorescence spectroscopy measurements are utilized to determine the optimal vesicle size, charge, bilayer thickness, and concentration for encapsulation and uptake. Cell viability, flow cytometry, and confocal microscopy are used to demonstrate safe and effective dosages, whereas knockdown of Bcl-2 protein expression was confirmed by Western blots.

Recent Advances in pH- or/and Photo-Responsive Nanovehicles

“…( B ) Illustration of the reversible transition of cationic vesicles to free surfactants with UV illumination. Reproduced from [ 32 ] with permission, copyright 2020, American Chemical Society.…”

“…As shown in Figure 1, the vesicle carriers formed from the longest trans-azoTAB showed higher siRNA and paclitaxel encapsulation and more effective transfection. The drug co-loading vesicle carriers can enhance cell death and anti-apoptotic B-cell lymphoma-2 protein suppression due to UV-triggered release of the drugs from the ruptured vehicles [32]. [32] with permission, copyright 2020, American Chemical Society.…”

“…The drug co-loading vesicle carriers can enhance cell death and anti-apoptotic B-cell lymphoma-2 protein suppression due to UV-triggered release of the drugs from the ruptured vehicles [32]. [32] with permission, copyright 2020, American Chemical Society.…”

“…The coumarinyl ester is irreversibly cleaved in response to UV light. Usually, coumarin is incorporated into a [32] with permission, copyright 2020, American Chemical Society.…”

Photo-Responsive Polymersomes as Drug Delivery System for Potential Medical Applications

“…Upon UV light irradiation, the hydrophobic block is transformed into an hydrophilic one in the photocleavage reaction of o-nitrobenzyl groups, thereby resulting in dissociation of the polymersomes with simultaneous co-release of both hydrophilic and hydrophobic cargoes. While the UV light could limit its application to a certain extent, many kinds of drug delivery systems respond to the UV irradiation, which has been prepared and studied in lots of labs [26,32,33]. We have reason to believe this unique on-demand releasing characteristic provides a noninvasive drug releasing strategy and could be applied in many clinical areas such as medical imaging and targeted therapy.…”