Active Drug Research Articles

The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.

Cancer is the second leading cause of global mortality and claims approximately 10 million lives annually. Despite advances in treatments such as surgery, chemotherapy, and immunotherapy, resistance to these methods has emerged. Multidrug resistance (MDR), where cancer cells resist diverse treatments, undermines therapy effectiveness, escalating mortality rates. MDR mechanisms include, among others, drug inactivation, reduced drug uptake, enhanced DNA repair, and activation of survival pathways such as autophagy. Moreover, MDR mechanisms can confer resistance to other therapies like radiotherapy. Understanding these mechanisms is crucial for improving treatment efficacy and identifying new therapeutic targets. Extracellular vesicles (EVs) have gathered attention for their role in cancer progression, including MDR development through protein transfer and genetic reprogramming. Autophagy, a process balancing cellular resources, also influences MDR. The intersection of EVs and autophagy further complicates the understanding of MDR. Both extracellular (exosomes, microvesicles) and intracellular (autophagic) vesicles contribute to therapy resistance by regulating the tumor microenvironment, facilitating cell communication, and modulating drug processing. While much is known about these pathways, there is still a need to explore their potential for predicting treatment responses and understanding tumor heterogeneity.

Drug and biomarker tissue levels in a randomized presurgical trial on exemestane alternative schedules.

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a pre-surgical study of alternative exemestane schedules. Postmenopausal women candidate for breast surgery for estrogen receptor-positive breast cancer were randomized to exemestane 25 mg once daily (QD), 25 mg three times/week (TIW), or 25 mg per/week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in non-malignant tissue. Estradiol was nearly suppressed in all groups in the non-malignant tissue (QD vs TIW p = .364 and QD vs QW p = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in non-malignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy.

Light-Controlled Bioorthogonal Chemistry Altered Natural Killer Cell Activity for Boosted Adoptive Immunotherapy.

Natural killer (NK) cell-based immunotherapy has received much attention in recent years. However, the practical application is still suffering from the decreased function, inadequate infiltration, and immunosuppressive microenvironment in solid tumor. Herein, we construct the light-responsive porphyrin Fe array-armed NK cells (denoted as NK@p-Fe) for cell behavior modulation via bioorthogonal catalysis. By installing cholesterol-modified porphyrin Fe molecules on NK cell surface, it forms a catalytic array with light-harvesting capabilities. This functionality transforms NK cells into cellular factories, capable of catalyzing the production of active agents in a light-controlled manner. The NK@p-Fe can generate active antineoplastic drug doxorubicin through bioorthogonal reactions to enhance the cytotoxic function of NK cells. Beyond drug synthesis, the NK@p-Fe can also bioorthogonally catalyze to produce FDA approved immune agonist, imiquimod (IMQ). The activated immune agonist plays a dual role by inducing DC maturation for NK cells activation and reshaping tumor immunosuppressive microenvironment for NK cells infiltration. This work represents a paradigm for modulation of adoptive cell behaviors to boost cancer immunotherapy by bioorthogonal catalysis.

Eco-friendly Approaches to Chromene Derivatives: A Comprehensive Review of Green Synthesis Strategies.

Synthetic routes of chromene are an area of thrust research due to its wide application as pigments, agrochemicals, cosmetics, and an important nucleus scaffold for various pharmaco-logically active drugs. The chromene nucleus is an important moiety for the discovery of new drug candidates owing to its broad range of pharmacological actions like antitumor, anti-inflammatory, antiviral, and many others. However, traditional synthesis techniques frequently use unsafe reagents and produce hazardous waste, presenting environmental issues. The eco-friendly production of chromene derivatives utilizes sustainable raw materials, non-toxic cata-lysts, and gentle reaction conditions to reduce ecological consequences. Innovative methods like microwave irradiation, ultrasound synthesis, the use of environmentally friendly solvents, a cata-lyst-based approach with minimal environmental impact, and mechanochemistry-mediated syn-thesis are implemented. These approaches provide benefits in scalability, cost-effectiveness, and ease of purification. This review compiles and presents various recently reported green synthetic strategies of chromene and its derivatives and gives the reader a clear idea of the detailed and crit-ical aspects of various synthetic protocols described.

Dysregulation of Human Hepatic Drug Transporters by Proinflammatory Cytokines.

Proinflammatory cytokines, elevated during inflammation caused by infection and/or autoimmune disorders, result in reduced clearance of drugs eliminated primarily by cytochrome P450 enzymes (CYPs). However, the effect of cytokines on hepatic drug transporter expression or activity has not been well-studied. Here, using plated human hepatocytes (PHHs; n=3 lots), we investigated the effect of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), on the mRNA expression and activity of hepatic drug transporters. PHHs were incubated for 72 hours at their pathophysiologically relevant plasma concentrations, both individually (0.01, 0.1, 1, 10 ng/mL) or as a cocktail (i.e., when each was combined at 0.1 or 1 ng/mL). Following cytokine cocktail exposure (1 ng/mL), significant downregulation of mRNA expression of organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, sodium/ taurocholate cotransporting polypeptide (NTCP), breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), multidrug and toxin extrusion protein 1 (MATE1), multi-drug resistance protein 2, 3, and 4 (MRP2/3/4) was observed. While the mRNA expression of organic anion transporter 2 (OAT2) and organic cation transporter 1 (OCT1) was downregulated in two lots, it was upregulated in one lot. In agreement (mostly), the 1 ng/mL cytokine cocktail reduced OATP1B1/3, OATP2B1, OAT2, OCT1, and NTCP activity by 75%, 44%, 82%, 47%, and 80%, respectively. Interestingly, upregulation of OAT2 and OCT1 mRNA in one donor did not translate into the same directional change in activity. Although significant inter-lot variability was observed, in general, the above effects, using individual cytokines, could be attributed to IL-1β and IFN-γ. Significance Statement To date, this is the first comprehensive study to investigate the effect of 4 major proinflammatory cytokines, both individually and as a cocktail, on the mRNA expression and activity of human hepatic drug transporters. The data obtained can be used in the future to predict transporter-mediated drug clearance changes during inflammation through physiologically-based pharmacokinetic modeling and simulation.

Racial and ethnic differences in self-reported barriers to substance use treatment among emergency department patients.

As overdose rates rise among non-White Americans, understanding barriers to substance use disorder (SUD) treatment access by race and ethnicity is important. This study explores self-reported barriers to SUD treatment by race and ethnicity in emergency department (ED) populations. We conducted a secondary, exploratory analysis of a randomized trial of patients not seeking SUD treatment who endorsed active drug use at six academic EDs. Responses to the Barriers to Treatment Inventory were compared by race, ethnicity, and drug severity, using χ2 tests (N = 858), followed by adjusted logistic regression models. Absence of a perceived drug problem (39% non-Hispanic Black, 38% Hispanic, 50% non-Hispanic White; p ≤ .001) was the most prevalent barrier to SUD treatment. Non-Hispanic Black participants were less likely to state that they could handle their drug use on their own (OR = 0.69, CI = 0.50-0.95), and were more likely to report disliking personal questions than non-Hispanic White participants (OR = 1.49, CI = 1.07-2.09). Non-Hispanic Black participants were less likely than Hispanic participants to agree that treatment availability (OR = 0.46, CI = 0.28-0.76) and family disapproval (OR = 0.38, CI = 0.16-0.91) were treatment barriers. Screening and counseling may help address the barrier, common to all groups, that drug use was not seen as problematic. Expanding access to diverse treatment options may also address the range of barriers reported by our study population. Our study is one of the first in the U.S. to examine both individual and structural barriers to accessing treatment and to examine the association with drug use severity by race/ethnicity.

Formulation and Evaluation of a Polyherbal Gel for Skin Disorders

The aim of the present investigation was to formulate and evaluate the herbal gel containing Marigold, Garlic, Honey, Cocoa Powder Aloe Vera for wound healing and antimicrobial potential. Marigold, Garlic, Honey, Cocoa Powder Aloe Vera used in the preparation possess an excellent anti-inflammatory, antioxidant and healing potential. Gelling agent used in this study was Carbopol 934P. In the present study five formulations containing different concentration of carbopol and honey were formulated and optimized. The optimized formulations were selected for further studies. Optimized gel was then loaded with active drug. The formulations were characterized for initial physicochemical parameters i.e. surface pH, spreadability, viscosity and antimicrobial susceptibility test to observe toxicity or side effects. The result revealed that the surface pH was within the range of skin pH. The viscosity and spreadability of the gel was appropriate and zone of inhibition was also satisfactory for optimized formulations G4 and G5. The preparations were stable under normal storage conditions and did not produce any skin irritation, i.e., erythema and oedema for about a month, when applied over the skin.

Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.

Tuberculosis (TB) remains a critical health threat, particularly with the emergence of multidrug-resistant strains. This demands attention from scientific communities and healthcare professionals worldwide to develop effective treatments. The enhanced intracellular survival (Eis) protein is an acetyltransferase enzyme of Mycobacterium tuberculosis that functions by adding acetyl groups to aminoglycoside antibiotics, which interferes with their ability to bind to the bacterial ribosome, thereby preventing them from inhibiting protein synthesis and killing the bacterium. Therefore, targeting this protein accelerates the chance of restoring the aminoglycoside drug activity, thereby reducing the emergence of drug-resistant TB. For this, we have screened 406,747 natural compounds from the Coconut database against Eis protein. Based on MM/GBSA rescoring binding energy, the top 5 most prominent natural compounds, viz. CNP0187003 (-96.14kcal/mol), CNP0176690 (-93.79kcal/mol), CNP0136537 (-92.31kcal/mol), CNP0398701 (-91.96kcal/mol), and CNP0043390 (-91.60kcal/mol) were selected. These compounds exhibited the presence of a substantial number of hydrogen bonds and other significant interactions confirming their strong binding affinity with the Eis protein during the docking process. Subsequently, the MD simulation of these compounds exhibited that the Eis-CNP0043390 complex was the most stable, followed by Eis-CNP0187003 and Eis-CNP0176690 complex, further verified by binding free energy calculation, principal component analysis (PCA), and Free energy landscape analysis. These compounds demonstrated the most favourable results in all parameters utilised for this investigation and may have the potential to inhibit the Eis protein. There these findings will leverage computational techniques to identify and develop a natural compound inhibitor as an alternative for drug-resistant TB.

Exploring the mechanism of Lianhuaqingwen (LHQW) in treating chronic bronchitis based on network pharmacology and experimental validation

BackgroundLianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis.MethodsThe research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets.ResultsA total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein–protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways.ConclusionThis research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.Graphical

Biotechnological potential of Brazilian snake venom in the production of biologically active drugs: Literature review

Despite being feared, Brazilian venomous snakes can be reservoirs of important resources of medicinal interest, since the venoms of these animals have an invaluable potential for biologically active substances found in nature. Pharmacological and biochemical studies carried out in recent decades have shown the diversity of proteins with enzymatic activity, toxins, peptides, bioactive amines, among other compounds in snake venoms. The aim of this literature review was to describe the pharmaceutical biotechnological potential of Brazilian snake venom and to demonstrate the importance of these toxins and their pharmacological derivatives for public health. Since 1894, when they were studied by Vital Brazil, molecules derived from Brazilian snake venom have shown significant biological activity. These molecules have been proven to be efficient antimicrobial, antifungal and antiprotozoal agents, mainly due to their activity as serine proteases, hyaluronidases, L-amino acid oxidases (LAAO) and acetylcholinesterases, among other well-known substances. Brazilian snake venoms have thus been the target of a series of studies, which have borne excellent fruit, for example in the development of various drugs, such as Captopril®, which is derived from a peptide isolated from the venom of Bothrops jararaca, and fibrin sealant, derived from molecules in the venom of Crotalus durissus terrificus associated with cryoprecipitate from the blood plasma of buffaloes. With the analysis of biotechnologies applied to various molecules with the capacity for pharmacological, biologically active action, it is clear that this field is vast for new research and due to the great diversity of compounds in snake venoms. Certainly, as research progresses, new biologically active drugs derived from snake venom should become available for use and benefit of the population. Thus, studies related to the chemical composition of snake venoms should be encouraged, as well as those related to their pharmaceutical biotechnological potential.

Network Pharmacology Combined with GEO Analysis of the Mechanism of Qing-Jin-Hua-Tan Decoction in the Treatment of Non-small Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is one of the most prevalent malignancies and poses a significant threat to human health. Qing-Jin-Hua-Tan (QJHT) decoction is a classical herbal remedy that has demonstrated therapeutic effects in various diseases, including NSCLC, and can improve the quality of life of patients with respiratory conditions. However, the mechanism underlying the effect of the QJHT decoction on NSCLC remains unclear and requires further investigation. We collected NSCLC-related gene datasets from the GEO database and performed differential gene analysis, followed by using WGCNA to identify the core set of genes associated with NSCLC development. The TCMSP and HERB databases were searched to identify the active ingredients and drug targets, and the core gene target datasets related to NSCLC were merged to identify the intersecting targets of drugs and diseases for GO and KEGG pathway enrichment analysis. We then constructed a protein-protein interaction (PPI) network map of drug diseases using the MCODE algorithm and identified key genes using topology analysis. The disease-gene matrix underwent immunoinfiltration analysis, and we analyzed the association between intersecting targets and immunoinfiltration. We obtained the GSE33532 dataset that met the screening criteria, and a total of 2211 differential genes were identified using differential gene analysis. We performed GSEA analysis and WGCNA analysis for a crossover with differential genes, resulting in 891 key targets for NSCLC. The drug database was screened to obtain 217 active ingredients and 339 drug targets of QJHT. By constructing a PPI network, the active ingredients of QJHT decoction were intersected with the targets of NSCLC, resulting in 31 intersected genes. Enrichment analysis of the intersection targets showed that 1112 biological processes, 18 molecular functions, and 77 cellular compositions were enriched in GO functions, and 36 signaling pathways were enriched in KEGG pathways. Based on immune-infiltrating cell analysis, we found that the intersection targets were significantly associated with multiple infiltrating immune cells. Our analysis using network pharmacology and mining of the GEO database revealed that QJHT decoction can potentially treat NSCLC through multi-target and multi-signaling pathways, while also regulating multiple immune cells.

Association of positive airway pressure termination with mortality and non-fatal cardiovascular events in patients with obstructive sleep apnoea

Background and aimsThe recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether...

Revealing the impact of modified modules flexibility on gemcitabine prodrug nanoassemblies for effective cancer therapy

Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.

Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials. We conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays. We immunostained microglia to characterize proliferation and clustering. We report CSF soluble TREM2 (sTREM2) and CSF chitinase-3-like protein 1 (CHI3L1/YKL-40) as PD biomarkers for the TREM2 agonist hPara.09. The respective reduction of sTREM2 and elevation of CHI3L1 in brain and CSF after TREM2 agonist treatment correlated with transient microglia proliferation and clustering. CSF CHI3L1 and sTREM2 reflect microglial TREM2 agonism and can be used as clinical PD biomarkers to monitor TREM2 activity in the brain. CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) reflects brain target engagement for a novel TREM2 agonist, hPara.09. CSF chitinase-3-like protein 1 reflects microglial TREM2 agonism. Both can be used as clinical fluid biomarkers to monitor TREM2 activity in brain.

Integrating single-cell transcriptomics and machine learning to predict breast cancer prognosis: A study based on natural killer cell-related genes.

Breast cancer (BC) is the most commonly diagnosed cancer in women globally. Natural killer (NK) cells play a vital role in tumour immunosurveillance. This study aimed to establish a prognostic model using NK cell-related genes (NKRGs) by integrating single-cell transcriptomic data with machine learning. We identified 44 significantly expressed NKRGs involved in cytokine and T cell-related functions. Using 101 machine learning algorithms, the Lasso + RSF model showed the highest predictive accuracy with nine key NKRGs. We explored cell-to-cell communication using CellChat, assessed immune-related pathways and tumour microenvironment with gene set variation analysis and ssGSEA, and observed immune components by HE staining. Additionally, drug activity predictions identified potential therapies, and gene expression validation through immunohistochemistry and RNA-seq confirmed the clinical applicability of NKRGs. The nomogram showed high concordance between predicted and actual survival, linking higher tumour purity and risk scores to a reduced immune score. This NKRG-based model offers a novel approach for risk assessment and personalized treatment in BC, enhancing the potential of precision medicine.

Prospects of Electrocorticography in Neuropharmacological Studies in Small Laboratory Animals

Electrophysiological methods of research are widely used in neurobiology. To assess the bioelectrical activity of the brain in small laboratory animals, electrocorticography (ECoG) is most often used, which allows the recording of signals directly from the cerebral cortex. To date, a number of methodological approaches to the manufacture and implantation of ECoG electrodes have been proposed, the complexity of which is determined by experimental tasks and logistical capabilities. Existing methods for analyzing bioelectrical signals are used to assess the functional state of the nervous system in test animals, as well as to identify correlates of pathological changes or pharmacological effects. The review presents current areas of applications of ECoG in neuropharmacological studies in small laboratory animals. Traditionally, this method is actively used to study the antiepileptic activity of new molecules. However, the possibility of using ECoG to assess the neuroprotective activity of drugs in models of traumatic, vascular, metabolic, or neurodegenerative CNS damage remains clearly underestimated. Despite the fact that ECoG has a number of disadvantages and methodological difficulties, the recorded data can be a useful addition to traditional molecular and behavioral research methods. An analysis of the works in recent years indicates a growing interest in the method as a tool for assessing the pharmacological activity of psychoactive drugs, especially in combination with classification and prediction algorithms.

A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44–0.84) and 0.67, 95 % CI (0.53–0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23–0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35–0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

Strategies for the development of stimuli-responsive small molecule prodrugs for cancer treatment

Approved anticancer drugs typically face challenges due to their narrow therapeutic window, primarily because of high systemic toxicity and limited selectivity for tumors. Prodrugs are initially inactive drug molecules designed to undergo specific chemical modifications. These modifications render the drugs inactive until they encounter specific conditions or biomarkers in vivo, at which point they are converted into active drug molecules. This thoughtful design significantly improves the efficacy of anticancer drug delivery by enhancing tumor specificity and minimizing off-target effects. Recent advancements in prodrug design have focused on integrating these strategies with delivery systems like liposomes, micelles, and polymerosomes to further improve targeting and reduce side effects. This review outlines strategies for designing stimuli-responsive small molecule prodrugs focused on cancer treatment, emphasizing their chemical structures and the mechanisms controlling drug release. By providing a comprehensive overview, we aim to highlight the potential of these innovative approaches to revolutionize cancer therapy.

Donor-Acceptor-Donor Strategy Rouses the Photodynamic Therapy Anticancer Activity of a Bis-terpyridyl Ru(II) Complex.

Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.

Do Molecular Fingerprints Identify Diverse Active Drugs in Large-Scale Virtual Screening? (No)

Do Molecular Fingerprints Identify Diverse Active Drugs in Large-Scale Virtual Screening? (No)