The development of simple, cost-effective, and advanced multifunctional technology is the need of the hour to combat cancer as well as bacterial infections. There have been reports of silver nanoparticles (AgNPs), silver salts, and Prussian blue (PB) being used for medicinal purposes which are clinically approved. In this context, in the present communication, we incorporated PB and silver salts (silver nitrate) to develop silver PB analogue nanoparticles (SPBANPs), a new nanomedicine formulation as a safer and effective mode of treatment strategy (2-in-1) for both cancer and bacterial infections. Considering all fundamental issues of nanomedicine, along with understanding of the biological impact of PB, we designed a simple, fast, efficient, cheap, and eco-friendly method for the synthesis of [poly­(N-vinyl-2-pyrrolidone)]-stabilized silver hexacyanoferrate nanoparticles (silver PB analogue: Ag3[Fe­(CN)6] abbreviated as SPBANPs). Various analytical tools were used to analyze and characterize the nanomaterials (SPBANPs). The SPBANPs were highly stable for several weeks in various phosphate buffers with a range of physiological pH conditions (pH = 6–8). The nanoparticles showed biocompatibility in vivo in C57BL6/J mice that encouraged us to screen the nanoparticles for various biomedical applications. The SPBANPs themselves exhibited remarkable inhibition of cancer cell proliferation (B16F10, A549, MCF-7, and SK-OV-3) in vitro. Substantial inhibition of melanoma tumor growth was observed in the C57BL6/J mouse model (aggressive murine melanoma model: B16F10) after intraperitoneal administration of the SPBANPs without any anticancer drug. Additionally, the SPBANPs exhibited excellent antibacterial activity in various Gram-negative (Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Interestingly, this nanoformulation itself works as a drug delivery vehicle, as well as an anticancer and antibacterial agent. The in vitro and in vivo results together demonstrate that this biocompatible nanoformulation (SPBANPs) without an anticancer drug or antibiotic could be explored to develop as a multifunctional therapeutic agent (2-in-1) for the treatment of cancer and bacterial infections in the near future.

Recent times have witnessed an upsurge in the incidence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Prion disease, and amyotrophic lateral sclerosis. The treatment of the same remains a daunting challenge due to the limited access of therapeutic moieties across the blood–brain barrier. Engineered nanoparticles with a size less than 100 nm provide multifunctional abilities for solving these biomedical and pharmacological issues due to their unique physico‐chemical properties along with capability to cross the blood–brain barrier. Needless to mention, there is a scarcity of review articles summarizing recent developments of various nanomaterials including liposomes, polymeric nanoparticles, metal nanoparticles, and bio‐nanoparticles toward the therapeutic and theranostics applications for various neurodegenerative disorders. Here, a broad spectrum of nanomedicinal approaches to eradicate neurodegenerative disorders is provided, along with a brief account of neuroprotection and neuronal tissue regeneration, current clinical status, issues related to safety, toxicity, challenges, and future outlook.

Background: M. tuberculosis evades host-immune-responses by polarizing T helper (Th)2 and regulatory T cell (Treg) responses, which diminish protective Th1 responses.Results: Mice that are unable to generate Th2 cells and Tregs are resistant to M. tuberculosis infection. Simultaneous inhibition of these T cell subsets by therapeutic compounds dramatically reduced bacterial burden.Conclusion: Inhibition of Th2 and Treg cells increases Th1 responses that protect against M. tuberculosis infection.Significance: As therapeutic agents employed here do not directly act on harbored pathogens, they should avoid generation of drug-resistant M. tuberculosis variants.

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Background: Immunological parameters induced by BCG and the requirement of immunologic responses for optimal vaccine efficacy is incompletely understood.Results: Small-molecule inhibitors of Th2 and Treg cells promote BCG vaccine efficacy.Conclusion: Immunomodulators enhance the capacity of the BCG vaccine to protect against tuberculosis.Significance: Our studies reveal a simple and cost-effective approach to improve BCG vaccine efficacy.

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Mycobacterium tuberculosis, the causative agent of tuberculosis, resides and replicates within susceptible hosts by inhibiting host antimicrobial mechanisms. Prostaglandin E(2) (PGE(2)), produced by M. tuberculosis-infected macrophages, exerts a variety of immunomodulatory functions via 4 receptors (EP1-EP4), each mediating distinct PGE(2) functions. Here, we show that M. tuberculosis infection selectively upregulates EP2 messenger RNA expression in CD4(+) T cells. We found that EP2 deficiency in mice increases susceptibility to M. tuberculosis infection, which correlated with reduced antigen-specific T-cell responses and increased levels of CD4(+)CD25(+)Foxp3(+) T-regulatory cells. These findings have revealed an important role for EP2 in host immune defense against tuberculosis. As a G protein-coupled receptor, EP2 could serve as a target for immunotherapy of tuberculosis.

Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha,beta-arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2–3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2−/− and IL-10−/− animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2−/− mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to be tested for prevention of recrudescence in falciparum and relapse in vivax malaria.