Vitamin k3-Loaded Magnetic Nanoparticle-Mediated Synergistic Magnetothermodynamic Therapy Evokes Massive ROS and Immune Modulation for Augmented Antitumor Potential.

Magnetic nanoparticle (MNP)-mediated magnetic hyperthermia (MHT) under an alternating magnetic field (AMF) causes tumor regression via reactive oxygen species (ROS) generation. However, less therapeutic efficacy has been reported due to the generation of low levels of ROS in a hypoxic tumor microenvironment. Therefore, improved treatments are required to generate relatively high levels of ROS to promote irreversible oxidative damage to the tumor cells. Herein, we report a magnetothermodynamic (MTD) therapy, as a robust and versatile approach for cancer treatment, by combining the magnetothermodynamic-related ROS and heat-related immunological effect in order to overcome the aforementioned obstacle. The synergistic therapy was achieved by the development of vitamin k3 (Vk3)-loaded copper zinc ferrite nanoparticles (Vk3@Si@CuZnIONPs) as an efficient MTD agent. The in vitro results unveiled that enhanced ROS production under the influence of AMF is a predominant aspect in yielding an assertive anticancer response. The in vivo antitumor response was assessed in an ectopic tumor model of A549 lung adenocarcinoma by MTD. The tumor inhibition rate of 69% was achieved within 20 days of MTD treatment, exhibiting complete tumor eradication within 30 days. The validation of antitumor response was marked by severe apoptosis (TUNEL, Caspase-3) in the Vk3@Si@CuZnIONPs + AMF-treated group. The higher expression level of heat shock proteins and proinflammatory cytokines (IL-6, TNF-α, IL-1α, IL-1ß) was speculated to play a role in the activation of immune response for faster tumor regression in the MTD-treated group. Therefore, by implementing a dual ROS and heat-mediated immunogenic effect, the antitumor efficiency of future cancer magnetotherapies will be greatly enhanced.

Extirpating the cancer stem cell hydra: Differentiation therapy and Hyperthermia therapy for targeting the cancer stem cell hierarchy.

Ever since the discovery of cancer stem cells (CSCs), they have progressively attracted more attention as a therapeutic target. Like the mythical hydra, this subpopulation of cells seems to contribute to cancer immortality, spawning more cells each time that some components of the cancer cell hierarchy are destroyed. Traditional modalities focusing on cancer treatment have emphasized apoptosis as a route to eliminate the tumor burden. A major problem is that cancer cells are often in varying degrees of dedifferentiation contributing to what is known as the CSCs hierarchy and cells which are known to be resistant to conventional therapy. Differentiation therapy is an experimental therapeutic modality aimed at the conversion of malignant phenotype to a more benign one. Hyperthermia therapy (HT) is a modality exploiting the changes induced in cells by the application of heat produced to aid in cancer therapy. While differentiation therapy has been successfully employed in the treatment of acute myeloid leukemia, it has not been hugely successful for other cancer types. Mounting evidence suggests that hyperthermia therapy may greatly augment the effects of differentiation therapy while simultaneously overcoming many of the hard-to-treat facets of recurrent tumors. This review summarizes the progress made so far in integrating hyperthermia therapy with existing modules of differentiation therapy. The focus is on studies related to the successful application of both hyperthermia and differentiation therapy when used alone or in conjunction for hard-to-treat cancer cell niche with emphasis on combined approaches to target the CSCs hierarchy.

Indispensable role of microbes in anticancer drugs and discovery trends.

Recent years have seen an increased focus on the advancement of naturally derived products for the treatment of cancer. Since the beginning of recorded history, nature has provided a variety of medicinal agents, and an overwhelming number of drugs that we have today are derived from natural sources. Such natural agents are prominently used to treat several diseases such as diabetes, malaria, Alzheimer's, pulmonary disorders, etc. with cancer being the highlight of this review. Due to the rapid development of resistance to chemotherapeutic drugs, the hunt for effective novel drugs is still a paramount concern in cancer treatment. Moreover, many chemotherapy drugs typically have high toxicity and adverse side effects, which necessitates the need to develop anti-tumor drugs that can be employed to treat deadly tumors with fewer negative effects on health and better efficacy. Isolation of several chemotherapeutic drugs has been conducted from a wide range of natural sources which include plants, microbes, fungi, and marine microorganisms. Considering the trends of previous decades, microbial diversity has grown to play a significant role in the formulation of pharmaceuticals and drugs, especially antibiotics and anti-cancer medications. Microbe-derived antitumor antibiotics such as anthracycline, epothilones, bleomycin, actinomycin, and staurosporine are amongst the widely used cancer chemotherapeutic agents. This review deals majorly with microbe-derived anticancer drugs taking into account their derivatives, mechanism of action, isolation procedures, limitations, and tumors targeted by them. This article also reports the phase of clinical study these drugs are undergoing. Moreover, it intends to portray the indispensable part that these microbes have been playing since time immemorial in the odyssey of chemotherapeutic agents. KEY POINTS: • Microbial diversity contributes heavily towards the formulation of anticancer drugs. • Polypeptides, carbohydrates, and alkaloids are prevalent microbe-based drug classes. • Microbe-derived anticancer agents target various sarcomas, carcinomas, and lymphomas.

Design of new bis-triazolyl structure for identification of inhibitory activity on COVID-19 main protease by molecular docking approach.

In the rapidly growing COVID-19 pandemic, designing of new drugs and evaluating their inhibitory action against main targets of corona virus could be an effective strategy to accelerate the drug discovery process and their efficacy towards corona virus disease. Herein, we design new bis-triazolyl probe for an investigation of inhibitory activity towards COVID-19 main protease by Molecular docking approach. The formulated compound has been thoroughly characterized by elemental analysis, NMR (1H and 13C) and complete structure elucidation was achieved via X-ray crystallography. Docking study reveals that newly synthesized compound confers good inhibitory response to COVID-19 main protease as supported by calculated docking score and binding energy. Strong hydrogen bonding and hydrophobic interactions of the newly synthesized compound with several important amino acids of the main protease also helps to explain the potency of the compound to inhibit the main protease. We hope that the present study would help the researcher in the field of Medicinal chemistry and to develop potential drug against the novel corona virus.