ArticleScientific reports2016
Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
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- Protein-based nanoparticles for therapeutic nucleic acid delivery.Biomaterials · 2024Review
- The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses.International journal of molecular sciences · 2023Review
- Nanotechnology - a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer.Beilstein journal of nanotechnology · 2023Review
- Engineering biomolecular systems: Controlling the self-assembly of gelatin to form ultra-small bioactive nanomaterials.Bioactive materials · 2022Article
- Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.Pharmaceutics · 2022Review
- KRAS mutation: from undruggable to druggable in cancer.Signal transduction and targeted therapy · 2021Review
- CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries.Cancer gene therapy · 2021Review
- Nanomedicine of tyrosine kinase inhibitors.Theranostics · 2021Review
- Review
- The Daniel K. Inouye College of Pharmacy Scripts: Targeted Nanocarrier Based Systems for the Treatment of Lung Cancer.Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health · 2017Review
- Shp2 regulates migratory behavior and response to EGFR-TKIs through ERK1/2 pathway activation in non-small cell lung cancer cells.Oncotarget · 2017Article
- Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation.Molecules (Basel, Switzerland) · 2017Review
- Cetuximab-siRNA Conjugate Linked Through Cationized Gelatin Knocks Down KRAS G12C Mutation in NSCLC Sensitizing the Cells Toward Gefitinib.Technology in cancer research & treatmentArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation.
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