Cetuximab-siRNA Conjugate Linked Through Cationized Gelatin Knocks Down KRAS G12C Mutation in NSCLC Sensitizing the Cells Toward Gefitinib.

Delivery of small-interfering RNA (siRNA) has been of great interest in the past decade for effective gene silencing. To overcome synthetic and regulatory challenges posed by nanoparticle-mediated siRNA delivery, antibody-siRNA conjugate (ARC) platform is emerging as a potential siRNA delivery system suitable for clinical translation. Herein, we have developed a delivery technology based on the ARC platform for stable delivery of siRNA called as Gelatin-Antibody Delivery System (GADS).

CRISPR-Cas deployment in non-small cell lung cancer for target screening, validations, and discoveries.

Continued advancements in CRISPR-Cas systems have accelerated genome research. Use of CRISPR-Cas in cancer research has been of great interest that is resulting in development of orthogonal methods for drug target validations and discovery of new therapeutic targets through genome-wide screens of cancer cells. CRISPR-based screens have also revealed several new cancer drivers through alterations in tumor suppressor genes (TSGs) and oncogenes inducing resistance to targeted therapies via activation of alternate signaling pathways.

Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown.

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.

Three-Dimensional Nanocomposites: Fluidics Driven Assembly of Metal Nanoparticles on Protein Nanostructures and Their Cell-Line-Dependent Intracellular Trafficking Pattern.

Three-dimensional nanocomposites prepared using two different families of nanomaterials holds significant relevance pertaining to biological applications. However, integration of the two distinct nanomaterials with precision to control the overall compositional homogeneity of the resulting 3D nanocomposite is a synthetic challenge. Conventional reactions result in nanocomposites with heterogeneous composition and render useless.

Polymeric nanoparticles for molecular imaging.

Conventional imaging technologies (X-ray computed tomography, magnetic resonance, and optical) depend on contrast agents to visualize a target site or organ of interest. The imaging agents currently used in clinics for diagnosis suffer from disadvantages including poor target specificity and in vivo instability. Consequently, delivery of low concentrations of contrast agents to region of interest affects image quality.