K-RAS driven non-small-cell lung cancer (NSCLC) represents a major cause of death among smokers. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Herein, we report a novel, multifunctional nanoceria platform loaded with a unique combination of two therapeutic drugs, doxorubicin (Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and effective treatment of NSCLC. We hypothesize that the use of ganetespib synergizes and accelerates the therapeutic efficacy of Doxo via ROS production, while minimizing the potential cardiotoxicity of doxorubicin drug. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles (PNC) were fabricated for the targeted combination therapy of lung cancers. Using "click" chemistry, the surface carboxylic acid groups of nanoceria were decorated with folic acid to target folate-receptor-overexpressing NSCLC. As a result of combination therapy, results showed more than 80% of NSCLC death within 48 h of incubation. These synergistic therapeutic effects were assessed via enhanced ROS, cytotoxicity, apoptosis, and migration assays. Overall, these results indicated that the targeted codelivery of Doxo and GT using nanoceria may offer an alternative combination therapy option for the treatment of undruggable NSCLC.

Rapid detection and diagnosis of pathogenic strains of influenza is necessary for expedited treatment and quicker resolutions to the ever-rising flu pandemics. Considering this, we propose the development of novel magnetic relaxation nanosensors (MRnS) for the rapid detection of influenza through targeted binding with hemagglutinin. 2,6- and 2,3-sialic acid ligands and entry blocker peptides are conjugated to iron oxide nanoparticles to create functional MRnS. Positive detection of various hemagglutinin variants (H1 and H5) is possible with protein concentrations as little as 1.0 nM. Most importantly, detection using functional MRnS is achieved within minutes and differentiates between influenza subtypes. This specificity allows mixtures of MRnS to screen for multiple pathogens at once, discarding the need to conduct multiple individual tests. Current methods used to diagnose influenza, such as RT-PCR and viral culturing, while largely effective, are complex, time-consuming and costly. As well, they are not as sensitive or specific, and have been known to produce false-positive results. In contrast to these methods, targeted MRnS are robust, point-of-care diagnostic tools featuring simple, rapid and low-cost procedures. These qualities, as well as high sensitivity and specificity, and low turnaround times, make a strong case for the diagnostic application of MRnS in clinical settings.

Purpose: K-RAS is the most common mutated oncogene associated with Non-Small-Cell Lung Cancer (NSCLC). So far, there are no promising chemotherapies for the direct inhibition of K-RAS, and considered to be undruggable. In this work, we have introduced a new platinum-based cyanoximate complex, Pt(MCO)2, as an anti-cancer drug to enhance the therapeutic efficacy of Hsp90 inhibitor drug, ganetespib for the combination therapy of NSCLC.Methods: We have synthesized polyacrylic acid (PAA)-coated magnetic nanoparticles (MNPs) and used as drug delivery system. These MNPs were decorated with folic acid in order to target folate receptor-expressing NSCLC. The individual and combination of drugs as well as an optical dye DiI were co-encapsulated successfully inside the PAA-coating of MNPs to evaluate synergistic treatment option for NSCLC. The magnetic resonance (MR) and optical imaging modalities assisted for the monitoring drug loading and NSCLC treatment.Results: To evaluate the therapeutic efficacy of these customized MNPs, various cell-based assays including cell viability, apoptosis and necrosis, cell migration, comet and ROS experiments were performed. Results showed minimal toxicity for functional MNPs with no therapeutic drug and more than 60% cell death within 48 h of treatment, when single drug was encapsulated. Importantly, more than 90% cells were dead when both drugs were delivered. Overall, the results indicated that the Pt(MCO)2 drug enhances the therapeutic efficacy of ganetespib by more than 30% toxicity towards the targeted treatment of NSCLC, while showed minimal toxicity to the normal healthy tissues.Conclusion: We successfully developed new dual-modal magnetic nanomedicines for the rapid and controlled release of combination of drugs for the effective treatment of NSCLC. The MR and fluorescence modalities help monitoring the delivery of drugs, where the new platinum-based drug Pt(MCO)2 synergizes the therapeutic efficacy of ganetespib.

<p>The biological activation and incorporation of inorganic sulfate proceeds via a process known as sulfurylation. Transfer of a sulfuryl moiety from the activated sulfate donor, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), to hydroxy-containing substrates by human phenol sulfotransferases (SULT1 family) alters substrate solubility and charge to affect the metabolism of endogenous metabolites, xenobiotics, and drugs. Current methods to monitor SULT1 activity in living cells primarily rely on radiolabeling and/or cell extractions, but these methods do not provide a direct readout of enzyme activity with a dynamic, temporally resolved spatial map in live, intact cells. To fill this gap, here, we present the development, computational modeling, <i>in vitro</i> enzymology, and biological application of Sulfotransferase Sensor-3, STS-3, an activity-based fluorescent sensor for SULT1A1, the most widely expressed and promiscuous SULT1 isoform. </p>