Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment

Kulkarni, Nishant S.; Parvathaneni, Vineela; Shukla, Snehal K.; Barasa, Leonard; Perron, Jeanette C.; Yoganathan, Sabesan; Muth, Aaron; Gupta, Vivek

doi:10.1016/j.ejps.2019.03.026

Cited by 49 publications

(15 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It works by inhibiting the maturation of platelets from megakaryocytes [ 68 ]. Moreover, desmethyl erlotinib is an EGFR inhibitor, and it was approved in 2004 to treat lung and pancreatic cancer [ 69 ]. All FDA-approved drugs identified have some known modes of actions and have shown the potent inhibition of VACV in the screens ( Table 1 ), suggesting a promising direction of exploring novel and safe antivirals for poxvirus infection.…”

Section: Resultsmentioning

confidence: 99%

Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs

et al. 2020

View full text Add to dashboard Cite

Four decades after the eradication of smallpox, poxviruses continue to threaten the health of humans and other animals. Vaccinia virus (VACV) was used as the vaccine that successfully eradicated smallpox and is a prototypic member of the poxvirus family. Many cellular pathways play critical roles in productive poxvirus replication. These pathways provide opportunities to expand the arsenal of poxvirus antiviral development by targeting the cellular functions required for efficient poxvirus replication. In this study, we developed and optimized a secreted Gaussia luciferase-based, simplified assay procedure suitable for high throughput screening. Using this procedure, we screened a customized compound library that contained over 3200 bioactives and FDA (Food and Drug Administration)-approved chemicals, most having known cellular targets, for their inhibitory effects on VACV replication. We identified over 140 compounds that suppressed VACV replication. Many of these hits target cellular pathways previously reported to be required for efficient VACV replication, validating the effectiveness of our screening. Importantly, we also identified hits that target cellular functions with previously unknown roles in the VACV replication cycle. Among those in the latter category, we verified the antiviral role of several compounds targeting the janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3) signaling pathway by showing that STAT3 inhibitors reduced VACV replication. Our findings identify pathways that are candidates for use in the prevention and treatment of poxvirus infections and additionally provide a foundation to investigate diverse cellular pathways for their roles in poxvirus replications.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Cellular uptake studies were performed using a protocol reported earlier [33]. Briefly, A549 cells were plated in tissue culture (TC) treated cell imaging cover-glass (8 chambers; Eppendorf, Hauppauge, NY, USA) at a seeding density of 10,000 cells/chamber followed by overnight incubation.…”

Section: Cellular Uptake Studiesmentioning

confidence: 99%

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

et al. 2020

Self Cite

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.

show abstract

“…The multiple-dose study was performed to evaluate and mimic the physiological conditions a treatment regimen may experience due to the drug metabolism and clearance from the body, which may require several dosages during the treatment regimen [56]. Briefly, after overnight incubation, the spheroids were treated with control, Met (10 mM), and Met DO lipo (10 mM), followed by removal of 100 µL of media, and replenishment with 100 µL of the respective treatment every three days.…”

Section: Resultsmentioning

confidence: 99%

Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

This study aimed at developing metformin hydrochloride (Met) encapsulated liposomal vesicles for enhanced therapeutic outcomes at reduced doses against breast cancer. Liposomal Met was prepared using thin-film hydration through various loading methods; passive loading, active loading, and drug-loaded lipid film. The drug-loaded film method exhibited maximum entrapment efficiency (~65%) as compared to active loading (~25%) and passive loading (~5%) prepared Met-loaded liposomes. The therapeutic efficacy of these optimized liposomes was evaluated for cellular uptake, cytotoxicity, inhibition of metastatic activity, and apoptosis-inducing activity. Results demonstrated significantly superior activity of positively charged liposomes resulting in reduced IC50 values, minimal cell migration activity, reduced colony formation, and profound apoptosis-induced activity in breast cancer cells as compared to Met. The anti-tumor activity was investigated using a clinically relevant in vitro tumor simulation model, which confirmed enhanced anti-tumorigenic property of liposomal Met over Met itself. To the authors’ knowledge, this is the first report of Met-loaded liposomes for improving the efficacy and therapeutic effect of Met against breast cancer. With the results obtained, it can be speculated that liposomal encapsulation of metformin offers a potentially promising and convenient approach for enhanced efficacy and bioavailability in breast cancer treatment.

show abstract

Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment

Cited by 49 publications

References 52 publications

Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs

Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer

Contact Info

Product

Resources

About