Omeprazole-Loaded Copper Nanoparticles for Mitochondrial Damage Mediated Synergistic Anticancer Activity against Melanoma Cells.

Metallic nanoparticles are promising candidates for anticancer therapies. Among the different metallic systems studied, copper is an affordable and biologically available metal with a high redox potential. Copper-based nanoparticles are widely used in anticancer studies owing to their ability to react with intracellular glutathione (GSH) to induce a Fenton-like reaction. However, considering the high metastatic potential and versatility of the tumor microenvironment, modalities with a single therapeutic agent may not be effective. Hence, to enhance the efficiency of chemotherapeutic drugs, repurposing them or conjugating them with other modalities is essential. Omeprazole is an FDA-approved proton pump inhibitor used in clinics for the treatment of ulcers. Omeprazole has also been studied for its ability to sensitize cancer cells to chemotherapy and induce apoptosis. Herein, we report a nanosystem comprising of copper nanoparticles encapsulating omeprazole (CuOzL) against B16 melanoma cells. The developed nanoformulation exerted significant synergistic anticancer activity when compared with either copper nanoparticles or omeprazole alone by inducing cell death through excessive ROS generation and subsequent mitochondrial damage.

PLGA nanoparticle loaded with antioxidants and photosensitizer for ROS shock mediated phototherapy of triple negative breast cancer.

The potential use of antioxidants for photodynamic therapy (PDT) is investigated in this study. PDT causes reactive oxygen species (ROS)-mediated cell death; on the contrary, antioxidants scavenge ROS. The use of a photosensitizer along with an antioxidant photosensitizer compensates for the loss of ROS due to the use of antioxidant, eventually leading to cell death. In this work, for PDT and photothermal therapy (PTT), we have combined the photosensitizer IR 792 perchlorate dye with the antioxidants alpha-tocopherol (A) andp-coumaric acid (C) encapsulated in a polymeric nanocarrier (AC IR NPs). We have reported the synthesis of AC IR NPs using poly lactic-co-glycolic acid (PLGA) by nanoprecipitation method. The size of the polymeric nanoparticles was found to be 80.4 ± 15.6 nm, with a spherical morphology observed by scanning electron microscopy and transmission electron microscopy. The synthesized AC IR NPs demonstrated good biocompatibility in fibroblast cell lines (L929). Furthermore, the efficacy assessment of the as prepared nanosystemin vitroon breast cancer cell lines (4T1) revealed a significant cell death of nearly 80%. This could be attributed to the ROS generation leading to oxidative stress and inhibition of metastasis. This study provides evidence that the combination of antioxidant drugs along with photosensitizers have the potential to be an effective therapy for treating triple negative breast cancer.

Advances in Peptide-Decorated Targeted Drug Delivery: Exploring Therapeutic Potential and Nanocarrier Strategies.

Peptides are ideal biologicals for targeted drug delivery and have also been increasingly employed as theranostic tools in treating various diseases, including cancer, with minimal or no side effects. Owing to their receptor-specificity, peptide-mediated drug delivery aids in targeted drug delivery with better pharmacological biodistribution. Nanostructured self-assembled peptides and peptide-drug conjugates demonstrate enhanced stability and performance and captivating biological effects in comparison with conventional peptides. Moreover, they serve as valuable tools for establishing interfaces between drug carriers and biological systems, enabling the traversal of multiple biological barriers encountered by peptide-drug conjugates on their journeys to their intended targets. Peptide-based drugs play a pivotal role in the field of medicine and hold great promise for addressing a wide range of complex diseases such as cancer and autoimmune disorders. Nanotechnology has revolutionized the fields of medicine, biomedical engineering, biotechnology, and engineering sciences over the past two decades. With the help of nanotechnology, better delivery of peptides to the target site could be achieved by exploiting the small size, increased surface area, and passive targeting ability of the nanocarrier. Furthermore, nanocarriers also ensure safe delivery of the peptide moieties to the target site, protecting them from degradation. Nanobased peptide delivery systems would be of significant importance in the near future for the successful targeted and efficient delivery of peptides. This review focuses on peptide-drug conjugates and nanoparticle-mediated self-assembled peptide delivery systems in cancer therapeutics.

Injectable Nano Whitlockite Incorporated Chitosan Hydrogel for Effective Hemostasis.

Uncontrolled bleeding can lead to many complications that might cause multiple organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca18Mg2(HPO4)2(PO4)12) that would release Ca2+, Mg2+, and PO43- ions that would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague-Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.