HeLa Cell-Derived Paclitaxel-Loaded Microparticles Efficiently Inhibit the Growth of Cervical Carcinoma

Abstract

Jinxia Peng,1,* Ju Zhao,2,* Yumei Zhao,2 Peng Wu,2 Lantu Gou,3 Shaozhi Fu,2 Ping Chen,2 Yun Lu,2 Linglin Yang2 1Department of Oncology, People’s Hospital of Xindu District, Chengdu, Sichuan 610500, People’s Republic of China; 2Department of Oncology, The Affiliated Hospital of Southwest Medical University Luzhou, Sichuan 646000, People’s Republic of China; 3West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linglin Yang Email [email protected]: Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma.Methods: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively.Results: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues.Conclusion: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.Keywords: cervical carcinoma, HeLa cells, microparticles, paclitaxel, vector

Keywords

• cervical carcinoma
• hela cells
• microparticles
• paclitaxel
• vector