Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening.

The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique susceptibility of the exposed individual. A critical target of IR is DNA, and the DNA damage response is a safeguard mechanism for maintaining genomic integrity in response to the induced cellular stress. Unrepaired DNA lesions lead to various mutations, contributing to adverse health effects. Cellular sensitivity to IR is highly correlated with the ability of cells to repair DNA lesions, in particular coding sequences of genes that affect that process and of others that contribute to preserving genomic integrity. However, accurate profiling of the molecular events underlying individual sensitivity requires techniques with sensitive readouts. Here we summarize recent studies that have used whole-genome analysis and identified genes that impact individual radiosensitivity. Whereas microarray and RNA-seq provide a snapshot of the transcriptome, RNA interference (RNAi) and CRISPR-Cas9 techniques are powerful tools that enable modulation of gene expression and characterizing the function of specific genes involved in radiosensitivity or radioresistance. Notably, CRISPR-Cas9 has altered the landscape of genome-editing technology with its increased readiness, precision, and sensitivity. Identifying critical regulators of cellular radiosensitivity would help tailor regimens that enhance the efficacy of therapeutic treatments and fast-track prediction of clinical outcomes. It would also contribute to occupational protection based on average individual sensitivity, as well as the formulation of countermeasures to the harmful effects of radiation.

Chitosan-based advanced materials for docetaxel and paclitaxel delivery: Recent advances and future directions in cancer theranostics.

Paclitaxel (PTX) and docetaxel (DTX) are key members of taxanes with high anti-tumor activity against various cancer cells. These chemotherapeutic agents suffer from a number of drawbacks and it seems that low solubility in water is the most important one. Although much effort has been made in improving the bioavailability of PTX and DTX, the low bioavailability and minimal accumulation at tumor sites are still the challenges faced in PTX and DTX therapy. As a consequence, bio-based nanoparticles (NPs) have attracted much attention due to unique properties. Among them, chitosan (CS) is of interest due to its great biocompatibility. CS is a positively charged polysaccharide with the capability of interaction with negatively charged biomolecules. Besides, it can be processed into the sheet, micro/nano-particles, scaffold, and is dissolvable in mildly acidic pH similar to the pH of the tumor microenvironment. Keeping in mind the different applications of CS in the preparation of nanocarriers for delivery of PTX and DTX, in the present review, we demonstrate that how CS functionalized-nanocarriers and CS modification can be beneficial in enhancing the bioavailability of PTX and DTX, targeted delivery at tumor site, image-guided delivery and co-delivery with other anti-tumor drugs or genes.