Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations

Abstract

Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately.

RETRACTED ARTICLE: Clinical practice of epidermal growth factor receptor-tyrosine kinase inhibitor targeted drugs combined with gadolinium oxide nanoparticles in the treatment of non-small cell lung cancer

“…In this experiment, hyaluronic acid gadolinium trioxide nanoparticles (HA-Gd2O3-NPs) were synthesized by hyaluronic acid, passivation molecule, and gadolinium chloride. Compared with normal lung tissue cells with low expression of EGFR, these new nanoparticles can specifically target lung cancer cells with high expression of EGFR, and can also realize active targeting to tumor cells through surface modified ligands Accurate drug delivery [ 12 ]. HA-Gd2O3-NPs, as a drug carrier, specifically targets EGFR mutant NSCLC cells and efficiently releases loaded drugs, which provides a new method for EGFR mutant lung cancer patients to overcome the resistance of EGFR-TKI.…”

Ligand conjugated lipid‐based nanocarriers for cancer theranostics

“…However, anionic SiRNA was coupled with cationic lipid ‐DOTAP whose linker was exposed on the surface of the carrier. The results demonstrated that this multicomponent delivery system has much higher anticancer efficacy (5−10‐fold) than individual components applied separately, which depicts the strong detecting ability of the system (Majumder & Minko, 2021). Overall, anti‐EGFR Fab′ and EGF conjugated NLBCs can bind to human tumor cells receptor with high specificity and selectivity.…”

Nanoparticles design considerations to co-deliver nucleic acids and anti-cancer drugs for chemoresistance reversal

“…Fluorophore rhodamine, which acts as an imaging agent, was loaded into the lipid phase during the synthesis process of the nanoparticles. The images showed that the rhodamine-labeled nanoparticles containing anticancer drugs and siRNA penetrated the lung cancer cells and localized in the cytoplasm, indicating successful cellular uptake of nanoparticles ( Majumder and Minko, 2021 ).…”