Exogenous application of nanocarrier-mediated double-stranded RNA manipulates physiological traits and defence response against bacterial diseases.

Stability and delivery are major challenges associated with exogenous double-stranded RNA (dsRNA) application into plants. We report the encapsulation and delivery of dsRNA in cationic poly-aspartic acid-derived polymer (CPP6) into plant cells. CPP6 stabilizes the dsRNAs during long exposure at varied temperatures and pH, and protects against RNase A degradation.

A localized hydrogel-mediated chemotherapy causes immunogenic cell death via activation of ceramide-mediated unfolded protein response.

Treatment of triple-negative breast cancer (TNBC) is challenging because of its "COLD" tumor immunosuppressive microenvironment (TIME). Here, we present a hydrogel-mediated localized delivery of a combination of docetaxel (DTX) and carboplatin (CPT) (called DTX-CPT-Gel therapy) that ensured enhanced anticancer effect and tumor regression on multiple murine syngeneic and xenograft tumor models. DTX-CPT-Gel therapy modulated the TIME by an increase of antitumorigenic M1 macrophages, attenuation of myeloid-derived suppressor cells, and increase of granzyme BCD8 T cells.

Hydrophobicity of Cholic Acid-Derived Amphiphiles Dictates the Antimicrobial Specificity.

The unique structural components of cell membranes of Gram-positive bacteria, Gram-negative bacteria, and mycobacteria provide an excellent therapeutic target for developing highly specific antimicrobials. Here, we report the synthesis of nine cholic acid (CA)-derived amphiphiles, where three hydroxyl groups of CA were tethered to dimethylamino pyridine and the C24-carboxyl group was conjugated with different alkyl chains. Structure-activity investigations revealed that amphiphile harboring a methyl group has antimicrobial activity against mycobacterial species.

Polyaspartate-derived synthetic antimicrobial polymer enhances the activity of rifampicin against multidrug-resistant infections.

Infections caused by multidrug-resistant () pose major challenges for treatment due to the acquired, adaptive, and intrinsic resistance developed by the bacteria. Accumulation of mutations, the ability to form biofilms, and the presence of lipopolysaccharides in the outer bacterial membranes are the key mechanisms of drug resistance. Here, we show that a polyaspartate-derived synthetic antimicrobial polymer (SAMP) with a hexyl chain (TAC6) is an effective adjuvant for a hydrophobic antibiotic, rifampicin.

Emerging biomedical applications of polyaspartic acid-derived biodegradable polyelectrolytes and polyelectrolyte complexes.

Polyelectrolytes (PELs) - polymers with charged repeat units - have emerged as a useful class of polymers for biomedical applications due to their high aqueous solubility, low aggregation propensity and the opportunity they afford for polyvalent interactions with surfaces. Biodegradability and biocompatibility of PELs are important prerequisites for their utilization in in vivo applications. PELs that can be chemically functionalized with ease prove advantageous for creating diverse biomaterials.

A Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism.

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.

Targeted SHP-1 Silencing Modulates the Macrophage Phenotype, Leading to Metabolic Improvement in Dietary Obese Mice.

Chronic over-nutrition promotes adipocyte hypertrophy that creates inflammatory milieu leading to macrophage infiltration and their phenotypic switching during obesity. The SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has been identified as an important player in inflammatory diseases involving macrophages. However, the role of SHP-1 in modulating the macrophage phenotype has not been elucidated yet.

A nanogel based oral gene delivery system targeting SUMOylation machinery to combat gut inflammation.

Poor success rates and challenges associated with the current therapeutic strategies of inflammatory bowel disease (IBD) have accelerated the emergence of gene therapy as an alternative treatment option with great promise. However, oral delivery of nucleic acids (NAs) to an inflamed colon is challenged by multiple barriers presented by the gastrointestinal, extracellular and intracellular compartments. Therefore, we screened a series of polyaspartic acid-derived amphiphilic cationic polymers with varied hydrophobicity for their ability to deliver NAs into mammalian cells.

Oral Delivery of Cholic Acid-Derived Amphiphile Helps in Combating Salmonella-Mediated Gut Infection and Inflammation.

A major impediment to developing effective antimicrobials against Gram-negative bacteria like Salmonella is the ability of the bacteria to develop resistance against existing antibiotics and the inability of the antimicrobials to clear the intracellular bacteria residing in the gastrointestinal tract. As the critical balance of charge and hydrophobicity is required for effective membrane-targeting antimicrobials without causing any toxicity to mammalian cells, herein we report the synthesis and antibacterial properties of cholic acid-derived amphiphiles conjugated with alkyl chains of varied hydrophobicity. Relative to other hydrophobic counterparts, a compound with hexyl chain (6) acted as an effective antimicrobial against different Gram-negative bacteria.