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.
Highlights
Lung cancer represents the most common cause of cancer deaths in both men and women worldwide [1]
The earlier generations of monofunctional nanocarriers were capable of delivering a single therapeutic agent to overcome the shortcomings of its bioavailability, stability, and control release
The system combines several innovative approaches developed for treating lung cancer cells that overexpressed epidermal growth factor (EGF) receptors: (1) cancer targeting by a ligand (LHRH)
Summary
Lung cancer represents the most common cause of cancer deaths in both men and women worldwide [1]. Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer, accounting for about 84% of cases [2]. The majority of NSCLC patients are diagnosed in the advanced or metastatic stage of the disease, when treatment options are limited to surgery, chemotherapy, few targeted therapies, and immunotherapy [2,3,4,5]. The limited clinical efficiency, toxicity, and development of resistance represent three critical barriers limiting progress in the therapy of NSCLC. Metastatic lung cancer almost always eventually acquires resistance against all types of therapies, leading to poor survival rate in patients [6,7,8,9]
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