Photo-Triggered Delivery of siRNA and Paclitaxel into Breast Cancer Cells Using Catanionic Vesicles.
Zumra Peksaglam SeidelXiaoyang ZhangMelanie A MacMullanNicholas Alexander GrahamPin WangaC Ted LeePublished in: ACS applied bio materials (2020)
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.
Keyphrases
- breast cancer cells
- flow cytometry
- cell death
- cell cycle arrest
- drug delivery
- cancer therapy
- induced apoptosis
- high resolution
- single molecule
- endothelial cells
- oxidative stress
- small molecule
- photodynamic therapy
- squamous cell carcinoma
- hyaluronic acid
- optical coherence tomography
- endoplasmic reticulum stress
- big data
- radiation therapy
- protein protein
- pluripotent stem cells
- monte carlo
- mass spectrometry
- energy transfer
- solar cells