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The serious drawbacks of the conventional treatment of pancreatic ductal adenocarcinoma (PDAC) such as nonspecific toxicity and high resistance to chemo and radiation therapy, have prompted the development and application of countless small interfering RNA (siRNA)‐based therapeutics. Recent advances in drug delivery systems hold great promise for improving siRNA‐based therapeutics and developing a new class of drugs, known as nano‐siRNA drugs. However, many fundamental questions, regarding toxicity, immunostimulation, and poor knowledge of nano‐bio interactions, need to be addressed before clinical translation. In this review, we provide recent achievements in the design and development of various nonviral delivery vehicles for pancreatic cancer therapy. More importantly, codelivery of conventional anticancer drugs with siRNA as a new revolutionary pancreatic cancer combinational therapy is completely discussed.

Detection of diphtheria toxin (DT) which is produced by Corynebacterium diphtheria, a zoonotic pathogen and a leading cause of diphtheria, is the critical step in the clinical laboratory. Traditional methods for DT detection are time consuming with low sensitivity. Herein, a localized surface plasmon resonance (LSPR) nanobioprobe has been developed based on specific immunological interactions between gold nanoparticles (GNPs) conjugated with monoclonal antibody and diphtheria toxoid in order for the rapid detection of DT. For this, plasmonic GNPs were conjugated to monoclonal antibodies covalently. The covalent conjugation has been confirmed by dynamic light scattering (DLS) and electrochemical techniques. Then, structural alterations of the conjugated antibody were monitored by circular dichroism (CD) and fluorescence spectroscopy methods. After that, the sensitivity of the nanobioprobe has been investigated via measuring the LSPR band λmax shifts of GNPs and LSPR sensitivity of nanobioprobe was compared with the ELISA method. Results suggested that this assay is highly selective and sensitive with a lower detection limit of about 10 ng/mL. The LSPR biosensor reduced the DT detection time from 2 or 3 days to less than 1 h compared with traditional methods. In conclusion, the investigation presents a rapid, sensitive, and selective method for the diagnosis of DT in clinical specimens.

Long non-coding RNAs (LncRNAs) are widely known for their various functions in cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classified into grades I to IV according to their malignant histological features with grade IV, also known as glioblastoma multiforme (GBM), displaying the highest level of malignancy. Thus, the search for differentially expressed LncRNAs in GBM versus low-grade glioma to uncover new insights into the molecular mechanisms of glioma progression have intensified. Bulk RNA sequencing pinpointed decreased expression of OBI1-AS1 in GBM compared to low-grade glioma samples. Subsequent single nuclei RNA sequencing revealed OBI1-AS1 to be a super-exclusive astrocyte marker with AUC = 0.99 and the potential to fully differentiate astrocytes from other brain cell types. Additional supplementary bioinformatics analysis exhibited OBI1-AS1 role in synaptic signal transduction and glutamatergic signaling. In addition, ChIP-Seq data were analyzed to explore transcription factors that can regulate OBI1-AS1 expression in neural cells. Results of Hi-C, methylation and ChIP-Seq analysis strongly suggest methylation of the CTCF binding site serving a central role in regulation of OBI1-AS1 expression via managing chromatin interactions. Our study indicated that lncRNAs, like OBI1-AS1, could be extremely precise in identifying the astrocyte cluster in the single-cell transcriptome and demonstrating superiority to well-established astrocyte markers such as GFAP, S100B, ALDH1L1, and AQP4. Graphical abstract

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