Current Pharmaceutical Design - Volume 31, Issue 10, 2025

Cardiovascular Diseases (CVDs) are the leading cause of global morbidity and mortality, necessitating innovative approaches for both therapeutics and diagnostics. Nanoscience has emerged as a promising frontier in addressing the complexities of CVDs.

This study aims to explore the interaction of CVDs and Nanomedicine (NMs), focusing on applications in therapeutics and diagnostics.

In the realm of therapeutics, nanosized drug delivery systems exhibit unique advantages, such as enhanced drug bioavailability, targeted delivery, and controlled release. NMs platform, including liposomes, nanoparticles, and carriers, allows the precise drug targeting to the affected cardiovascular tissues with minimum adverse effects and maximum therapeutic efficacy. Moreover, Nanomaterial (NM) enables the integration of multifunctional components, such as therapeutic agents and target ligands, into a single system for comprehensive CVD management. Diagnostic fronts of NMs offer innovative solutions for early detection and monitoring of CVDs. Nanoparticles and nanosensors enable highly sensitive and specific detection of Cardiac biomarkers, providing valuable insights into a disease state, its progression, therapeutic outputs, etc. Further, nano-based technology via imaging modalities offers high high-resolution imaging, aiding in the vascularization of cardiovascular structures and abnormalities. Nanotechnology-based imaging modalities offer high-resolution imaging and aid in the visualization of cardiovascular structures and abnormalities.

The cross-talk of CVDs and NMs holds tremendous potential for revolutionizing cardiovascular healthcare by providing targeted and efficient therapeutic interventions, as well as sensitive and early detection for the improvement of patient health if integrated with Artificial Intelligence (AI).

The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments.

This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2.

Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1.

Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.

About 10-15% of all breast cancers comprise triple-negative breast cancer (TNBC), defined as cancer cells that lack ER, PR, and HER2 protein receptors. Due to the absence of these receptors, treating TNBC using conventional chemotherapy is challenging and, therefore, requires the discovery of novel chemotherapeutic agents derived from natural sources.

The current work was intended to study the potential phytochemicals of Ajwa dates (Phoenix dactylifera L.) with the predicted potential targets (namely, Akt and PI3K) to determine possible TNBC inhibitors.

We harnessed network pharmacology, molecular docking, drug-likeness studies, Molecular Dynamics (MD) simulation, and binding free energy (MM-GBSA) calculation to get phytochemicals with potential effects against TNBC. Firstly, molecular docking was performed on 125 phytochemicals against the Akt and PI3K proteins utilizing PyRx. Then, the phytochemicals with the highest binding affinity (≤ -8.1 kcal/mol) were examined for in silico drug-likeness and toxicity profiles. Finally, phytochemicals with optimal drug-likeness and toxicity profiles were studied by Molecular Dynamics (MD) simulation and binding free energy (MM-GBSA) to identify compounds that can form stable complexes.

The results of the network pharmacology revealed that the Akt and PI3K proteins are potential targets of TNBC for the phytochemicals of Phoenix dactylifera L. used in this study. The outcomes of molecular docking displayed that among 125 phytochemicals, 42 of them (with a binding affinity ≤ -8.1 kcal/mol) have potentially inhibiting effects on both proteins PI3K and Akt expressed in TNBC. Then, the results of in silico drug-likeness identified seven phytochemicals with optimal pharmacokinetic profiles. Furthermore, toxicity studies showed that three phytochemicals (namely, Chrysoeriol, Daidzein, and Glycitein) did not cause any toxicities. Finally, the Molecular Dynamics (MD) simulation studies and binding free energy (MM-GBSA) verified that Daidzein stayed within the binding cavities of both proteins (Akt and PI3K) by establishing a stable protein-ligand complex during simulation.

Taken together, the current work emphasizes the potential effects of Daidzein from Phoenix dactylifera L. against TNBC, and it can be further studied to establish it as a standard chemotherapy for TNBC.

Dryopteris ramosa is a high-altitude plant of moist and shady habitat. Its aerial parts are edible and orally administered as an antibiotic and effective aphrodisiac. They are also used as pesticides, astringents, and febrifuges.

The present study aimed to elucidate the plant's medicinal potential as an anticancer agent. Extracts of Dryopteris ramosa were examined for cytotoxic effects against AGS, A549, and HCT116 cell lines. The project also aimed to evaluate the phytochemical constitutents of the plant. For this purpose, GC-ToF-MS analysis was executed to identify the bioactive compounds in the aerial parts extract of Dryopteris ramosa. As a result, 93 different phytochemicals were identified from the spectral properties of GC-ToF-MS which contain 19 compounds of high peaks having reported anti-inflammatory, Anti-diabetic, Antibacterial, Analgesic, and antioxidant potential.

Three different cell lines have been treated against Ethanol, Methanol, Ethyl acetate, Water, Chloroform, Acetone, and n-hexane extracts from the aerial parts of Dryopteris ramosa. These cell lines were checked and were ranked in lethality based on IC50 value. The extract samples were processed as serial dilution from high concentrations (500 ug/ml). All the three cell lines were treated for 48 hours.

Extracts showed a significant effect in different cell lines (based on IC50 less than 200 ug/ml). Performing the in vitro anticancer activity against the three different cell lines in Ethyl Acetate, Methanol, n-hexane, Chloroform and Acetone extract of Dryopteris indicated that anticancer activity of the plant is high against AGS and A549 cell line while less prominent in HTC116 cell lines through MTT Assay. In silico drug-likeness and ADMET analysis were studied of the compounds, that exhibit considerable drug likenesses, phytochemical medicinal chemistry, and a promising ADMET score and no toxicity. The candidate compounds were chosen for further elucidation by Molecular Docking and dynamic simulations. Employing the molecular docking approach for virtual screening of the phytochemicals it was found that the compounds Germacrene showed remarkable results towards BCL2 with -7 Kcal/Mol and a-D-(+)-Xylopyranose showed significant docking results towards 5P21 with -7.1 Kcal/Mol.

For multi-scale frames structural aberrations and fluctuations identification of the docked complexes, a molecular dynamics analysis was performed for a 100 ps simulation run by accessing the online tool of MDweb simulations. These molecular docking and simulation analyses also revealed that both the phytochemicals have a stable interaction with the cancer-related proteins BCL2 and 5P21.