Rapid proliferation of cancer cells assisted by endothelial cell-mediated angiogenesis and acquired inflammation at the tumor microenvironment (TME) lowers the success rate of chemotherapeutic regimens. Therefore, targeting these processes using localized delivery of a minimally toxic drug combination may be a promising strategy. Here, we present engineering of a biocompatible self-assembled lithocholic acid-dipeptide derived hydrogel (TRI-Gel) that can maintain sustained delivery of antiproliferating doxorubicin, antiangiogenic combretastatin-A4 and anti-inflammatory dexamethasone. Application of TRI-Gel therapy to a murine tumor model promotes enhanced apoptosis with a concurrent reduction in angiogenesis and inflammation, leading to effective abrogation of tumor proliferation and increased median survival with reduced drug resistance. In-depth RNA-sequencing analysis showed that TRI-Gel therapy induced transcriptome-wide alternative splicing of many genes responsible for oncogenic transformation including sphingolipid genes. We demonstrate that TRI-Gel therapy targets the reversal of a unique intron retention event in β-glucocerebrosidase 1 (Gba1), thereby increasing the availability of functional Gba1 protein. An enhanced Gba1 activity elevates ceramide levels responsible for apoptosis and decreases glucosylceramides to overcome drug resistance. Therefore, TRI-Gel therapy provides a unique system that affects the TME via post-transcriptional modulations of sphingolipid metabolic genes, thereby opening a new and rational approach to cancer therapy.

The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gramnegative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid−peptide conjugates (CAPs), demonstrating that valine− glycine dipeptide-derived CAP 3 is the most effective antimicrobial. Molecular dynamics simulations and structural analysis revealed that a precise intramolecular network of CAP 3 is maintained in the form of evolving edges, suggesting intramolecular connectivity. Further, we found high conformational rigidity in CAP 3 that confers maximum perturbations in bacterial membranes relative to other small molecules. Interestingly, CAP 3-coated catheters did not allow the formation of biofilms in mice, and treatment of wound infections with CAP 3 was able to clear the bacterial infection. Our results demonstrate that molecular conformation and internal connectivity are critical parameters to describe the antimicrobial nature of compounds, and the analysis presented here may serve as a general principle for the design of future antimicrobials.

Recently, there has been an increased interest in iron–gold-based hybrid nanostructures, due to their combined outstanding optical and magnetic properties resulting from the usage of two separate metals. The synthesis of these nanoparticles involves thermal decomposition and modification of their surfaces using a variety of different methods, which are discussed in this review. In addition, different forms such as core–shell, dumbbell, flower, octahedral, star, rod, and Janus-shaped hybrids are discussed, and their unique properties are highlighted. Studies on combining optical response in the near-infrared window and magnetic properties of iron–gold-based hybrid nanoparticles as multifunctional nanoprobes for drug delivery, magnetic–photothermal heating as well as contrast agents during magnetic and optical imaging and magnetically-assisted optical biosensing to detect traces of targeted analytes inside the body has been reviewed.

In this study,w ed escribe the engineering of sub-100 nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel(DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS,D TX-PC NMs do not cause any systemic toxicity and slowthe decayrate of plasma DTX concentration in rodents and non-rodent species including non-human primates.W ef urther demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNAm ethyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore,t his unique system has the potential to improve the quality of life in cancer patients and can be translated as anext-generation chemotherapeutic.