Melanin-Ce6-loaded polydopamine nanoparticles-based enhanced phototherapy for B16 melanoma cancer cells.

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer.

Carboxylic acid derivatives suppress the growth of Aspergillus flavus through the inhibition of fungal alpha-amylase.

Aspergillus favus (A. flavus) is a saprophytic fungus and a pathogen affecting several important foods and crops, including maize. A. flavus produces a toxic secondary metabolite called aflatoxin. Alpha-amylase (α-amylase), a hydrolytic enzyme produced by A. Flavus helps in the production of aflatoxin by hydrolysing the starch molecules in to simple sugars such as glucose and maltose. These simple sugars induce the production of aflatoxin. Inhibition of α-amylase has been proven as a potential way to reduce the production of aflatoxin. In the present study, we investigated the effect of selected carboxylic acid derivatives such as cinnamic acid (CA), 2, 4-dichlorophenoxyacetic acid (2,4-D), and 3-(4-hydroxyphenyl)-propionic acid (3,4-HPPA) on the fungal growth and for the α-amylase inhibitory activity. The binding potentials of these compounds with α-amylase have been confirmed by enzyme kinetics and isothermal titration calorimetry. Molecular docking and MD simulation studies were also performed to deduce the atomic level interaction between the protein and selected ligands. The results indicated that CA, 2,4-D and 3,4-HPPA can inhibit the fungal growth which could be partly due to the inhibition on fungal α-amylase activity.Communicated by Ramaswamy H. Sarma.

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.

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.

Development of a Point-of-Care Cervico-Vaginal Sampling/Testing Device for the Colorimetric Detection of Cervical Cancer.

This paper reports the colorimetric analysis of cervical-cancer-affected clinical samples by the in situ formation of gold nanoparticles (AuNPs) formed with cervico-vaginal fluids collected from healthy and cancer-affected patients in a clinical setup, termed "C-ColAur". We evaluated the efficacy of the colorimetric technique against the clinical analysis (biopsy/Pap smear) and reported the sensitivity and specificity. We investigated if the aggregation coefficient and size of the nanoparticles responsible for the change in color of the AuNPs (formed with clinical samples) could also be used as a measure of detecting malignancy. We estimated the protein and lipid concentrations in the clinical samples and attempted to investigate if either of these components was solely responsible for the color change, enabling their colorimetric detection. We also propose a self-sampling device, CerviSelf, that could enable the rapid frequency of screening. We discuss two of the designs in detail and demonstrate the 3D-printed prototypes. These devices, in conjugation with the colorimetric technique C-ColAur, have the potential to be self-screening techniques, enabling women to undergo rapid and frequent screening in the comfort and privacy of their homes, allowing a chance at an early diagnosis and improved survival rates.

High-Affinity DNA Nanomatrix: A Platform Technology for Synergistic Drug Delivery and Photothermal Therapy.

With the advent of nucleosome/nucleotide intercalating drugs, DNA-based nanocarriers have recently gained impetus. However, most of the newly proposed DNA nanosystems are rather complex, thereby having low scalability and translatability. In this study, we propose a simple DNA nanomatrix core encapsulated within a chitosan shell, which is expected to enhance the encapsulation efficiency of intercalating drugs. This has been demonstrated using proflavine hemisulfate (PfHS), a model intercalating agent that shows improved ROS generation, among other anticancerous properties. The release of the drug from the nanomatrix is triggered by providing a heat trigger using IR-792 perchlorate, a known NIR photothermal sensitizer.

Assessment of Epidemiological Indicators for Evaluation of National Malaria Elimination Programme: A Retrospective Study.

Background: Malaria has been one of India's most considerable health problems since 1940. The objective of our study is to determine the status of the National Malaria Elimination Programme in India by using epidemiological indicators. Methods and Materials: The annual reports of malaria for the years 2014-2021 and monthly reports for 2020 and 2021 were collected from the official web portal and were analysed for study specific assessments. Results: The API has shown a statistically significant reduction from 2017-2021 in all states along with category-1(P=0.003) and category-2(P=0.029) states/UTs, but there was no statistically significant reduction from 2017-2021 in category-3 (P=0.166) states/UTs. The zero indigenous cases had not been achieved in category-1 states/UTs. The overall percentage reduction in number of malaria cases in 2020 at the national level compared with 2014 was 83.6%. Despite states with strong health systems such as Gujarat, Maharashtra and Karnataka, have not shown zero indigenous cases in 2020 and the malaria cases noted were very far from reaching the targets. Conclusions: Although we observed a significant drop in malaria incidence from 2014 to 2020, demonstrating that the country is moving nearer to malaria elimination, it is crucial to implement the strategies to reduce Plasmodium falciparum% and re-establish surveillance programmes and execute national and state programmes in order to achieve the success of the National Malaria Elimination Programme. The recategorization of states/UTs are in accordance to the API, and implementation strategies were also needed.

Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India.

BACKGROUND: Thrombocytopenia is generally alarming to both clinicians and patients as the consequence can be disastrous. However, some of the conditions associated with thrombocytopenia can be innocuous. Unless this is recognized, detection of thrombocytopenia results in series of further investigations and management plan by clinicians. Hematological investigation in an apparently healthy/asymptomatic individual can throw up many surprises. One of them is thrombocytopenia and giant platelets on peripheral smear examination. Asymptomatic constitutional macrothrombocytopenia (also called as Harris platelet syndrome) is increasingly recognized in north and eastern parts of India. However, this condition is nearly unknown in southern part of our country. With Increased immigrants to south India from northern and eastern states, it becomes imperative for both clinicians and lab physicians to be aware of the magnitude of the condition and interpret appropriately. This can avoid unnecessary anxiety and investigations. MATERIALS AND METHODS: Blood samples from 300 north and northeastern immigrants (Cases) and equal number of healthy subjects from south India (Controls) were examined for hematological parameters. Peripheral smears were examined for the presence of giant platelets. Results: Constitutional macrothrombocytopenia was seen in 4.3% of the cases and in 0.66% of the controls. The difference was statistically significant with a Fischer exact P value of 0.0067. The prevalence of macrothrombocytopenia on subjective assessment of peripheral smear was 6.7% in the cases and 1% in the control group. CONCLUSIONS: The prevalence of Harris platelet syndrome was found to be 4.3% in the immigrants from north and northeastern states.