Lung carcinoma therapy using epidermal growth factor receptor‑targeted lipid polymeric nanoparticles co‑loaded with cisplatin and doxorubicin.
ONCOLOGY REPORTS(2019)
Abstract
The rate of lung cancer in tuberculosis (TB) patients is 7 to 30% higher than that in healthy individuals. Conventional chemotherapy of lung cancer shows limited efficiency due to poor tumor tissue drug accumulation and nonspecific cytotoxicity. Epidermal growth factor receptor (EGFR) is a promising target, which is overexpressed in lung carcinomas. In the present study, EGFR-targeted nanoparticles were constructed and co-delivered cisplatin (CDDP) and doxorubicin (DOX) for lung cancer therapy. In the present research, EGF-PEG-DSPE was synthesized. Then, EGFR-targeted lipid polymeric nanoparticles (LPNs) were fabricated, which consisted of a CDDP-loaded hybrophobic polymeric core, a DOX-loaded phospholipid layer, and an outer layer of EGF-PEG-DSPE ligand. The particle size, zeta potential, stability, release behavior of LPNs were characterized. The antitumor ability of LPNs were assessed in vitro and in vivo. EGFR-targeted LPNs loaded with CDDP and DOX (EGF C/D LPNs) had a size of 141.6 nm, and could encapsulate over 80% of feed drugs. Dual drug-loaded LPNs showed synergistic effects with a combination index (CI) of 0.57. EGF C/D LPNs showed the smallest tumor volume (253 mm(3)), with a tumor inhibition ratio of 74.5%. In summary, EGF C/D LPNs were stable and released the drugs in a sustained manner. In vitro and in vivo studies revealed that EGF C/D LPNs exhibited improved anticancer activity along with lower toxicity. These results indicated the best efficiency of EGF C/D LPNs for lung carcinoma therapy.
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Key words
lung carcinoma,epidermal growth factor receptor,combinatorial therapy,lipid polymeric nanoparticles,cisplatin,doxorubicin
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