Breast cancer, the most commonly diagnosed disease worldwide, has been linked to the overexpression of the kinesin Eg5 protein, a spindle motor protein crucial for the assembly and maintenance of the bipolar spindle during mitosis. This makes Eg5 an attractive therapeutic target for tumor treatment. To address the urgent need for effective treatments for this life-threatening illness, we utilized generative AI to design novel and potential inhibitors of this protein. In this study, a generative LSTM model was pretrained on SMILES data from ChEMBL and subsequently fine-tuned using SMILES of compounds with reported activity against the Eg5 protein. The fine-tuned model generated valid compounds, which were screened using a machine learning model, drug-likeness filters, molecular docking, and molecular dynamics (MD) simulations conducted over 200 ns. Five novel compounds with better binding affinities to Eg5 compared to the co-crystallized ligand were identified. The top compound, Compound 103 (a bioisostere of the co-crystallized ligand), demonstrated a significantly improved binding free energy (-82.68 kcal/mol) compared to the co-crystallized ligand (-76.98 kcal/mol), as determined by MM-GBSA calculations. ADMET predictions and MD simulations further confirmed that the top compounds interacted effectively with the target protein and exhibited drug-like properties. This study shows the potential of generative AI to explore our vast chemical space and find promising drug candidates. However, further in vitro and in vivo studies are needed to confirm the predicted biological effects of the top compounds.

We have studied the endocytic mechanisms that determine subcellular localization for three carrier-free chemotherapeutic-photothermal (chemo-PTT) combination ionic nanomedicines (INMs) composed of doxorubicin (DOX) and an near-infrared (NIR) dye (ICG, IR820, or IR783). This study aims to understand the cellular basis for previously published enhanced toxicity results of these combination nanomedicines toward MCF-7 breast cancer cells. The active transport mechanism of INMs, unlike free DOX, which is known to employ passive transport, was validated by conducting temperature-dependent cellular uptake of the drug in MCF-7 cells using confocal microscopy. The internalization pathway of these INMs was further probed in the presence and absence of different endocytosis inhibitors. Detailed examination of the mode of entry of the carrier-free INMs in MCF-7 cells revealed that they are primarily internalized through clathrin-mediated endocytosis. In addition, time-dependent subcellular localization studies were also investigated. Examination of time-dependent confocal images indicated that the INMs targeted multiple organelles, in contrast to free DOX that primarily targets the nucleus. Collectively, the high cellular endocytic uptake in cancerous cells (EPR effect) and the multimode targeting ability demonstrated the main reason for the low half-maxima inhibitory concentration (IC50) value (the high cytotoxicity) of these carrier-free INMs as compared to their respective parent chemo and PTT drugs.

Herein, a detailed investigation of nanodrugs derived by combining a chemotherapy (chemo) and photothermal therapy (PTT) approaches to enhance chemo drug efficacy is presented. Tamoxifen and its metabolite; N-desmethyltamoxifen are the selected chemo drugs that were electrostatically attached with a PTT agent, NaIR820, via a metathesis approach to develop two different ionic material (IM)-based chemo-PTT drugs. Ionic nanomaterials (INMs) were synthesized using reprecipitation method, and these carrier- free nanoparticles were characterized in detail. Photophysical properties of NaIR820 parent compound, and their derived chemo-PTT IMs and INMs revealed significant alterations in absorption and fluorescence emission spectra of IR820. Photophysical results demonstrated that INMs exhibited promising characteristics as photothermal agents that are beneficial for light mediated therapy. Photothermal conversion efficiency and reactive oxygen quantum yield of INMs and IMs also improved significantly in comparison to the parent NaIR820 compound. In vitro cell viability studies demonstrated improved dark and light cytotoxicity of chemo-PTT INMs as compared to treatments that involved either the mixture of both soluble parent drugs and chemo or PTT drugs independently. Moreso, apoptotic cell death signal was greatly enhanced for the INMs as opposed to the parent chemo drugs.

Synergistic combination therapy approach offers lots of options for delivery of materials with anticancer properties, which is a very promising strategy to treat a variety of malignant lesions with enhanced therapeutic efficacy. The current study involves a detailed investigation of combination ionic nanomedicines where a chemotherapeutic drug is coupled with a photothermal agent to attain dual mechanisms (chemotherapy (chemo) and photothermal therapy (PTT)) to improve the drug's efficacy. An FDA-approved Doxorubicin hydrochloride (DOX·HCl) is electrostatically attached with a near-infrared cyanine dye (ICG, IR783, and IR820), which serves as a PTT drug using ionic liquid chemistry to develop three ionic material (IM)-based chemo-PTT drugs. Carrier-free ionic nanomedicines (INMs) are derived from ionic materials (IMs). The photophysical properties of the developed combination IMs and their INMs were studied in depth. The phototherapeutic efficiency of the combination drugs was evaluated by measuring the photothermal conversion efficiency and singlet-oxygen quantum yield. The improved photophysical properties of the combination nanomedicines in comparison to their parent compounds significantly enhanced INMs' photothermal efficiency. Cellular uptake, dark and light toxicity studies, and cell death mechanisms of the chemo-PTT nanoparticles were also studied in vitro. The combination INMs exhibited enhanced cytotoxicity compared to their respective parent compounds. Moreover, the apoptosis cell death mechanism was almost doubled for combination nanomedicine than the free DOX, which is attributed to enhanced cellular uptake. Examination of the combination index and improved in vitro cytotoxicity results revealed a great synergy between chemo and PTT drugs in the developed combination nanomedicines.

A wide range of analytical strategies and approaches have been developed, accomplishing significant advances in searching for efficient, fast, reliable, sensitive, and accurate protocols for sample analysis in recent decades. Chemical sensors are also low-cost, portable, and ecologically friendly, making them a preferred method of choice for a broad spectrum of sample analysis in various matrices of complexity. Of particular interest are sensors based on fluorescent molecules, nanoparticles, nanoclusters, quantum dots, carbon nanotubes, molecularly imprinted polymers, sol-gels, dyes, porphyrins, ionic liquids, organized media, and fluorescent sensor arrays in microfluidic chips. This review highlights and provides concise and in-depth coverage of recent innovations, challenges, advances, and applications of a variety of fluorescence-based sensors for sample analysis between 2018 and 2022. Emphasis is placed on instrumentation design and the applications of sensors in analytical, environmental, pharmaceutical, agricultural, food, and forensic sample analysis. Recent innovations and the practical utility of fluorescent chemical sensors relevant to biological systems, biomedical sample measurements, and clinical diagnosis are extensively reviewed. Future directions and trajectories of fluorescent chemical sensors for various utilities, applications, and sample measurements are highlighted and discussed.

Plastics are in high demand for various uses worldwide because of their low cost, versatility, lightweight, low density, flexibility, high strength, and durability. An increase in single-use plastics and ineffective solid waste disposal and recycling strategies have resulted in a global microplastic (MP) pollution epidemic, with negative implications for the ecosystem and public health safety. Analytical methods, including thermogravimetry and chromatography, have been developed to detect MPs. Nevertheless, molecular spectroscopy methods such as Near Infrared (NIR), Fourier Transform Infrared (FTIR), Raman, and fluorescence spectroscopy for MP analysis have gained attention in recent years due to their rapidity, low cost, accuracy, and portability of spectrometers. This review article provides in-depth coverage of the survey of current literature on the challenges, toxicity, sample pretreatment, and spectroscopic (Fluorescence, Raman, FTIR) and real-time (satellite imagery, unmanned aerial vehicles, and aquatic drone technology) microplastic detection methods. Machine learning, micro-hyperspectral imaging, and chemometrics approach to microplastic detections are discussed. The challenges, future directions, and prospects for decreasing global MP pollution and their analysis are discussed.

This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin. Carrier-free ionic nanomedicines were then prepared by using the reprecipitation method. The photophysical characterization of parent porphyrin, ionic materials, and ionic nanomaterials, including absorbance, fluorescence and phosphorescence emission, quantum yield, radiative and nonradiative rate, and lifetimes, was performed. The results revealed that the counteranion significantly affects the photophysical properties of porphyrin. The ionic nanomaterials exhibited an increase in the reactive oxygen yield and enhanced cytotoxicity toward the MCF-7 cancer cell line. Examination of results revealed that the ionic materials exhibited an enhanced photodynamic therapeutic activity with a low IC50 value (nanomolar) in cancerous cells. These nanomedicines were mainly localized in the mitochondria. The improved light cytotoxicity is attributed to the enhanced photophysical properties and positive surface charge of the ionic nanomedicines that facilitate efficient cellular uptake. These results demonstrate that ionic material-based nanodrugs are promising photosensitizers for photodynamic therapy.

Fӧrster resonance energy transfer (FRET)-based systems are widely applicable in many areas of interest. In this study, a novel FRET-based ionic material (IM) was synthesized by pairing carbazole imidazolium cation (CI+) with fluorescein anion (Fl2-) through a simple ion-exchange method. The resulting IM ([CI]2[Fl]) was converted into an ionic nanoparticle (INP) in aqueous media for practical use for bioimaging application. The photophysical properties of the parent dyes, [CI]2[Fl], and INP were studied in detail. All FRET parameters were calculated in the synthesized material. [CI]2[Fl] exhibited a significant spectral overlap integral and an ideal theoretical FRET distance. The presence of the FRET mechanism was verified by the observed decrease in donor fluorescence lifetime and a moderate FRET efficiency in [CI]2[Fl]. The INP formed from [CI]2[Fl] was evaluated for use as a fluorescent pH probe and bioimaging agent. FRET efficiency of INP is calculated in a series of pH studies which indicates the highest efficiency at physiological pH. Whereas no FRET phenomenon is observed in highly acidic and basic conditions. The pH-dependent photophysical properties of [CI]2[Fl] are monitored and allow for the potential application as a fluorescent probe for the detection of acidic tissues in biological systems. The FRET-capable INP showed superior bioimaging capability in vitro as compared to the parent dye.

In this study, the application of ionic materials as a combination antibiotic drug was investigated. The fluoroquinolone, Norfloxacin, was converted into the ionic form and combined with the cationic dye, IR780+, using an ion-exchange reaction. The resulting ionic combination drug possesses two killing mechanisms in one compound. The antibiotic chemical mechanism along with the photothermal mechanism that was acquired by adding IR780 to the compound led to the development of a combination antibiotic drug. This ionic combination drug consisting of Norfloxacin anion and IR780 cation is easily dispersed in water using sonication waves. The parent compounds and ionic combination drug, dissolved in organic solvent and dispersed in water, were characterized, and the photophysical properties were studied in detail. It was discovered that the aqueous ionic combination drugs exhibited significant changes in absorbance and photoluminescent properties. In aqueous media, the dispersed ionic combination drug exhibited a very broad absorbance with an additional peak around 1000 nm which is advantageous in photothermal. A significant decrease in the quantum yield along with enhanced non-radiative rate constant was observed for the combination drug in the aqueous. The photothermal mechanism is present in both the parent IR780 dye and the ionic combination drug. The ionic combination drug displayed a high light-to-heat conversion efficiency and temperature increase similar to the parent dye. The combination of both killing mechanisms in the ionic combination drug resulted in enhanced antibacterial activity against Escherichia coli as compared to the parent Norfloxacin and IR780-I individually.

Fuel cells are a promising alternative to non-renewable energy production industries such as petroleum and natural gas. The cathodic oxygen reduction reaction (ORR), which makes fuel cell technology possible, is sluggish under normal conditions. Thus, catalysts must be used to allow fuel cells to operate efficiently. Traditionally, platinum (Pt) catalysts are often utilized as they exhibit a highly efficient ORR with low overpotential values. However, Pt is an expensive and precious metal, posing economic problems for commercialization. Herein, advances in carbon-based catalysts are reviewed for their application in ORRs due to their abundance and low-cost syntheses. Various synthetic methods from different renewable sources are presented, and their catalytic properties are compared. Likewise, the effects of heteroatom and non-precious metal doping, surface area, and porosity on their performance are investigated. Carbon-based support materials are discussed in relation to their physical properties and the subsequent effect on Pt ORR performance. Lastly, advances in fuel cell electrolytes for various fuel cell types are presented. This review aims to provide valuable insight into current challenges in fuel cell performance and how they can be overcome using carbon-based materials and next generation electrolytes.

Herein, an ionic material (IM) with Förster Resonance Energy Transfer (FRET) characteristics is reported for the first time. The IM is designed by pairing a Nile Blue A cation (NBA+) with an anionic near-infrared (NIR) dye, IR820−, using a facile ion exchange reaction. These two dyes absorb at different wavelength regions. In addition, NBA+ fluorescence emission spectrum overlaps with IR820− absorption spectrum, which is one requirement for the occurrence of the FRET phenomenon. Therefore, the photophysical properties of the IM were studied in detail to investigate the FRET mechanism in IM for potential dye sensitized solar cell (DSSCs) application. Detailed examination of photophysical properties of parent compounds, a mixture of the parent compounds, and the IM revealed that the IM exhibits FRET characteristics, but not the mixture of two dyes. The presence of spectator counterion in the mixture hindered the FRET mechanism while in the IM, both dyes are in close proximity as an ion pair, thus exhibiting FRET. All FRET parameters such as spectral overlap integral, Förster distance, and FRET energy confirm the FRET characteristics of the IM. This article presents a simple synthesis of a compound with FRET properties which can be further used for a variety of applications.

Herein, an inexpensive commercially available sensor is presented for the detection of 4-nitrophenol (4NP) pollutant. Sodium fluorescein (NaFl) is used as a sensor to detect trace amounts of 4NP in acetonitrile (MeCN). The photophysical properties of NaFl were studied in two different solvents, MeCN (aprotic) and water (protic), with varying concentrations of different nitroaromatics using UV-visible absorption and fluorescence spectrophotometry. In an aqueous medium, photophysical properties of NaFl did not change in the presence of nitroaromatics. However, examination of the photodynamics in MeCN demonstrated that NaFl is extremely sensitive to 4NP (limit of detection: 0.29 µg/mL). This extreme specificity of NaFl towards 4NP when dissolved in MeCN, as compared to other nitroaromatics, is attributed to hydrogen bonding of 4NP with NaFl in the absence of water, resulting in both static and dynamic quenching processes. Thus, NaFl is demonstrated as a simple, inexpensive, sensitive, and robust optical turn off sensor for 4NP.

High operational costs of modern medical devices and the required specialized, skilled personnel with certifications to operate most medical instrumentation remains a challenge and an impediment to rapid medical diagnosis and clinical analysis. The simplicity, portability, and ease of operation makes Raman spectrometers appealing for rapid medical diagnosis and clinical analysis at an affordable cost. Besides, the combined use of Raman spectroscopy and multivariate analyses has further facilitated effective pattern recognition providing accurate classification, and/or differentiation of biological and clinical samples. This review article highlights recent advances in Raman spectroscopy in medical diagnosis and clinical analysis between January 2018 and December 2020. Recent innovations in the use of Raman spectroscopy for chemical analysis in human specimens are discussed. Applications of Raman spectroscopy in cancer immunotherapy, cancer imaging, and detecting disease biomarkers in clinical samples are further highlighted. The review article highlights recent innovations in the use of Raman spectroscopy for the detection of various pathogens in human specimens. Moreover, recent innovations of combined uses of Raman spectroscopy and multivariate regression analyses for pattern recognition, and/or classification of clinical samples are discussed. Furthermore, insights into the projection in the use of Raman spectroscopy in medical diagnosis and clinical sample analysis are discussed.