Efficient Delivery of Gemcitabine by Estrogen Receptor-Targeted PEGylated Liposome and Its Anti-Lung Cancer Activity In Vivo and In Vitro

Abstract

Lung cancer is one of the main causes of cancer-related deaths. At present, the main treatment method for lung cancer is chemotherapy. Gemcitabine (GEM) is widely applied in lung cancer treatment, but its lack of targeting ability and serious side effects limit its application. In recent years, nanocarriers have become the focus of research to solve the above problems. Here, we prepared estrone (ES)-modified GEM-loaded PEGylated liposomes (ES-SSL-GEM) for enhanced delivery by identifying the overexpressed estrogen receptor (ER) on lung cancer A549 cells. We studied the characterization, stability, release behavior, cytotoxicity, targeting ability, endocytosis mechanism, and antitumor ability to prove the therapeutic effect of ES-SSL-GEM. The results showed that ES-SSL-GEM presented a uniform particle size of 131.20 ± 0.62 nm, a good stability, and a slowly released behavior. Moreover, ES-SSL-GEM enhanced tumor-targeting ability, and the endocytosis mechanism studies confirmed that the ER-mediated endocytosis had the most crucial effect. Furthermore, ES-SSL-GEM had the best inhibitory effect on A549 cell proliferation and significantly suppressed the tumor growth in vivo. These results suggest that ES-SSL-GEM is a promising agent for treating lung cancer.

Recent Advances in Targeted Drug Delivery Strategy for Enhancing Oncotherapy

“…Tang et al produced estrone (ES)-modified gemcitabine (GEM)-loaded PEGylated liposomes (ES-SSL-GEM) for enhancing delivery efficiency by identifying estrogen receptors overexpressed on lung cancer A549 cells. The findings showed that ES-SSL-GEM, which has good stability, can reduce drug leakage during blood circulation and enhance tumor-targeted effect [ 31 ].…”

Recent Advances in Micro- and Nano-Drug Delivery Systems Based on Natural and Synthetic Biomaterials

“…As a result of the interaction between the receptor and the linker, HA has the potential to bind to the CD44 receptor, which is overexpressed in certain cancer cells. As a consequence of this, HA-modified nanoparticles have the potential to assist in the diagnosis and treatment of cancer [22][23][24]. Dopamine-modified HA was used to coat the surface of iron oxide nanoparticles in a study carried out by Wang and co-workers [25].…”