Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Abstract

Bo Liu, Li Han, Junyan Liu, Shumei Han, Zhen Chen, Lixi Jiang Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji’nan, People’s Republic of China Background: Cervical cancer is a major world health problem for women. Currently, cancer research focuses on improving therapy for cervical cancer using various treatment options such as co-delivery of chemotherapeutic agents by nanocarriers.Purpose: The aim of this study was to develop trans-activating transcriptional activator (TAT)-modified solid lipid nanoparticles (SLNs) for co-delivery of paclitaxel (PTX) and α-tocopherol succinate-cisplatin prodrug (TOS-CDDP) (TAT PTX/TOS-CDDP SLNs) in order to achieve synergistic antitumor activity against cervical cancer.Methods: Lipid prodrug of CDDP (TOS-CDDP) and TAT-containing polyethylene glycol-distearoyl-phosphatidylethanolamine (TAT-PEG-DSPE) were synthesized. TAT PTX/TOS-CDDP SLNs were prepared by emulsification and solvent evaporation method. Physicochemical characteristics of SLNs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells.Results: TAT PTX/TOS-CDDP SLNs could be successfully internalized by HeLa cells and showed a synergistic effect in the suppression of cervical tumor cell growth. They exhibited high tumor tissue accumulation, superior antitumor efficiency, and much lower toxicity in vivo.Conclusion: The present study indicates that the co-delivery system provides a promising platform as a combination therapy for the treatment of cervical cancer, and possibly other types of cancer as well. Keywords: cervical cancer, lipid-based prodrug, combination therapy, solid lipid nanoparticles, cell-penetrating peptide

Keywords

• Cervical cancer
• lipid-based prodrug
• combination therapy
• solid lipid nanoparticles
• cell-penetrating peptide