Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system

Abstract

Context: Cardiotoxicity and myelosuppression of etoposide (ETP) limited its clinical application. Targeted drug delivery system could deliver anticancer agents to the target cancerous cells, thus reducing their toxicity. Objective: In this study, folate (FA) was applied for the construction of nanostructured lipid carriers (NLCs), and used for targeted delivery of ETP to tumors overexpresses the FA receptors. Methods: FA-poly (ethylene glycol)-distearoylphosphatidylethanolamine was synthesized. FA decorated and ETP-loaded NLCs (FA-ETP-NLCs) were prepared and the formulation was optimized by Box-Behnken design. Their particle size (PS), zeta potential and drug encapsulation efficiency (EE) was evaluated. In vitro cytotoxicity studies of FA-ETP-NLCs were tested in CT26, SGC7901, NCI-H209 cell lines. In vivo antitumor efficacies of the carriers were evaluated on mice bearing CT26 cells xenografts. Results: The optimum FA-ETP-NLCs formulations had a PS of 120.86 nm. The growth of CT26, SGC790 or NCI-H209 cells in vitro was obviously inhibited. FA-ETP-NLCs also displayed the best antitumor activity than other formulations in vivo. Conclusion: The results demonstrated that FA-ETP-NLCs were efficient in selective delivery to CT26, SGC790 or NCI-H209 cells overexpressing the FA receptors. Also, FA-ETP-NLCs can sufficiently transfer ETP to the cancer cells, enhance the antitumor capacity. Thus, FA-ETP-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.

Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation

“…Folic acid (FA) has a very high affinity for the FRs with a minimal effect on its binding ability even after conjugation with other nanomaterials. Therefore FA can significantly enhance the capability of nanoparticle-based delivery systems to target cancer cells 51 , 52 . In this study, we modified the liposome surface with folate and determined the average number of the folate molecules per liposome (estimated to be approximately 480) based on the total amount of folate and liposomes in the sample.…”

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

“…Many studies have attempted to solve the adverse side effects of ETP treatment and understand the underlying molecular mechanisms, e.g., multi-drug resistance [347], or unwanted toxicity [348]. The search for compounds that may improve ETP treatment usually starts with cell-based experiments, e.g., protective compounds shielding healthy cells [349], compounds selectively enhancing ETP toxicity [350] or targeted delivery [351]. …”

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Smart Drug Delivery Systems in the Treatment of Glioblastoma Multiforme

“…Folate is one of the commonly used small molecules as a ligand for targeted therapy, since the folate receptor is highly expressed in various types of cancer cells such as lung cancer, colon cancer, and GBM. Zhang et al [ 73 ] developed NLCs decorated with folate targeted delivery of etoposide (ETP) (FA-ETP-NLCs). In vitro cytotoxicity of FA-ETP-NLCs was investigated in three cell lines, i.e., CT26, SGC7901, and NCI-H209, and had IC 50 values three to four times higher than ETP-NLCs which illustrated higher suppression efficacy after targeting with folate.…”