Curcumin-loaded alginate hydrogels for cancer therapy and wound healing applications: A review.

Hydrogels have emerged as a versatile platform for a numerous biomedical application due to their ability to absorb a huge quantity of biofluids. In order to design hydrogels, natural polymers are an attractive option owing to their biocompatibility and biodegradability. Due to abundance in occurrence, cost effectiveness, and facile crosslinking approaches, alginate has been extensively investigated to fabricate hydrogel matrix. Management of cancer and chronic wounds have always been a challenge for pharmaceutical and healthcare sector. In both cases, curcumin have been shown significant improvement and effectiveness. However, the innate restraints like poor bioavailability, hydrophobicity, and rapid systemic clearance associated with curcumin have restricted its clinical translations. The current review explores the cascade of research around curcumin encapsulated alginate hydrogel matrix for wound healing and cancer therapy. The focus of the review is to emphasize the mechanistic effects of curcumin with its fate inside the cells. Further, the review discusses different approaches to designed curcumin loaded alginate hydrogels along with the parameters that regulates their release behavior. Finally, the review is concluded with emphasize on some key aspect on increasing the efficacy of these hydrogels along with novel strategies to further develop curcumin loaded alginate hydrogel matrix with multifacet applications.

Alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles for active mitochondrial targeting and radiosensitization enhancement in hepatocellular carcinoma.

The ability of some tumours to impart radioresistance serves as a barrier in the cancer therapeutics. Mitochondrial metabolism significantly persuades this cancer cell survival, incursion and plays a crucial role in conferring radioresistance. It would be of great importance to target the active mitochondria to overcome this resistance and achieve tumoricidal efficacy. The current report investigates the improved radiosensitization effect (under Gamma irradiation) in hepatocellular carcinoma through active mitochondrial targeting of alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles (GNP). The loading of a chemotherapeutic drug N-(4-hydroxyphenyl)retinamide in GNP allows adjuvant chemotherapy, which further sensitizes cancerous cells for radiotherapy. The GNP shows a drug loading efficiency of 8.5 wt% with a sustained drug release kinetics. The X-Ray diffraction (XRD) pattern and High-Resolution Transmission Electron microscopy (HRTEM) indicates the synthesis of core iron oxide nanoparticles with indications of a thin layer of gold shell on the surface with 1:7 ratios of Fe: Au. The GNP application significantly reduced per cent cell viability in Hepatocellular carcinoma cells through improved radiosensitization at 5 Gy gamma radiation dose. The molecular mechanism revealed a sharp increment in reactive oxygen species (ROS) generation and DNA fragmentation. The mitochondrial targeting probes confirm the presence of GNP in the mitochondria, which could be the possible reason for such improved cellular damage. In addition to the active mitochondrial targeting, the currently fabricated nanoparticles work as a potent Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) contrast agent. This multifunctional therapeutic potential makes GNP as one of the most promising theragnostic molecules in cancer therapeutics.

Genistein nanoformulation promotes selective apoptosis in oral squamous cell carcinoma through repression of 3PK-EZH2 signalling pathway.

BACKGROUND: Overexpression of polycomb protein contributes to epigenetic repression in oral squamous cell carcinoma (OSCC) ensuing in poor prognosis and aggressive phenotype. Several plant-based compounds could help prevent epigenome alteration and cancer progression, but their low bioavailability limits their therapeutic activity. HYPOTHESIS: In this study, we have synthesized genistein nanoformulation (GLNPs) and evaluated its epigenetic regulation mechanism for selective apoptosis induction in OSCC. METHODS: Lactalbumin was used to prepare nanoformulation of Genistein. The mechanism of epigenetic regulation and selective apoptosis by Genistein loaded nanoparticles was studied in OSCC cell line JHU011 and fibroblast cell line L929 using immunofluorescence, Western blotting and ChIP-qPCR assay. RESULTS: We have found that GLNPs treatment selectively induced apoptosis in OSCC compared to the normal fibroblast cells. This selective effect in OSCC is achieved through enhanced reactive oxygen species (ROS) generation followed by Bax mitochondrial translocation and caspase 3 activation. Further, GLNPs induced withdrawal of epigenetic transcription repression through concurrent downregulation of the polycomb group proteins (PcG) Bmi 1 and EZH2 along with their successive targets, UbH2AK119 and H3K27me3, which have immense therapeutic implications in the treatment of OSCC. Last, we have established that GLNPs regulate EZH2expression through proteasomal mediated degradation and 3PK inhibition; 3PK protein was found physically linked with EZH2 protein and its promoter region (-1107 to -1002). This event indicates that 3PK might play some crucial role in EZH2 expression and epigenetic control of OSCC. Moreover, the formulation showed improved biodistribution, aqueous dispersibility and enhanced biocompatibility In-vivo. CONCLUSIONS: These results provide evidence that GLNPs may withdraw epigenetic transcriptional repression and selectively induce apoptosis in human oral squamous cell carcinoma.