EGFR-targeted immunoliposomes efficiently deliver docetaxel to prostate cancer cells

Abstract

Prostate cancer is the second cause of cancer death in men worldwide. Docetaxel (DTX), an antimitotic drug, is widely used for the treatment of metastatic prostate cancer patients.Taxotere ® is a commercial DTX formulation. It contains a polysorbate 80 surfactant to improve DTX aqueous solubility, which has been associated with hypersensitivity reactions in patients. Liposomes have been used as promising delivery systems for a range of hydrophobic drugs, such as DTX, offering improved drug water solubility and biocompatibility, without compromising its anticancer activity. Herein, DTX-loaded liposomes were developed using the Box-Behnken factorial design. The optimized formulation was nano-sized, homogenous in size (67.47 nm) with high DTX encapsulation efficiency (99.95%). The encapsulated DTX was in a soluble amorphous state, which was slowly released. Next, to increase the liposomes selectivity to prostate cancer cells, cetuximab, an anti-EGFR monoclonal antibody. was successfully conjugated to the surface of liposomes, without compromising cetuximab protein structure and stability. As expected, our results showed higher cellular uptake and toxicity of immunoliposomes, compared to non-targeted liposomes, in DU145 (EGFRoverxpressing) prostate cancer cells. To the best of our knowledge, this is the first report of engineering EGFR-targeted liposomes to enhance the selectivity of DTX delivery to EGFR-positive prostate cancer cells.

Reversed‐phase high‐performance liquid chromatography: A fast and efficient analytical method to quantify docetaxel‐loaded pegylated liposomes in release study

“…At the end of the study, the percentage of DTX released PEG-LIP was 24.81% ± 1.20. Eloy et al and Von Zuben et al [42,48] obtained similar results in their studies.…”

“…The study of in vitro drug release is an important parameter to predict the possible effects in biological models [42,45,48]. Thus, in our work the release profile of Docetaxel encapsulated in pegylated liposomes was evaluated using Franz diffusion cells.…”

A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

“…Similarly, the epidermal growth factor receptor (EGFR) that is highly expressed in some prostate adenocarcinomas constituted an important target. Cetuximab, an anti-EGFR monoclonal antibody conjugated to liposomes-containing DTX, showed higher cellular uptake and cytotoxicity as well as enhanced the selectivity of DTX targeting and delivery to prostate cancer cells [25]. In other studies, conjugation of DTX to specific ligands shows increased solubility and targeting [26], controlled-release, and low systemic toxicity [25,27].…”

“…Cetuximab, an anti-EGFR monoclonal antibody conjugated to liposomes-containing DTX, showed higher cellular uptake and cytotoxicity as well as enhanced the selectivity of DTX targeting and delivery to prostate cancer cells [25]. In other studies, conjugation of DTX to specific ligands shows increased solubility and targeting [26], controlled-release, and low systemic toxicity [25,27]. Nanoformulation techniques using various nanocarriers have also provided sustained release at adequate concentrations and have thus greatly improved DTX targeting to tumors [17].…”

Folate-functionalized SMMC-7721 liver cancer cell membrane-cloaked paclitaxel nanocrystals for targeted chemotherapy of hepatoma

“…The rapid development of nanotechnology provides new ideas for the treatment and diagnosis of cancer (Manzur et al., 2017 ; He et al., 2018 ; Dong et al., 2019 ). Currently, various nanocarriers, such as mesopore silica (He et al., 2017 ), liposomes (Eloy et al., 2020 ), carbon nanotubes (Soleyman et al., 2015 ), polymer nanoparticles (Levit et al., 2020 ), and cyclodextrin nanoparticles (Yan et al., 2019 ), have been widely incorporated with PTX to improve its solubility and targeting ability.…”