title: Effects of anti-CD44 monoclonal antibody IM7 carried with chitosan polylactic acid-coated nano-particles on the treatment of ovarian cancer.
abstract: Failure in early diagnosis and ineffective treatment are the major causes of ovarian cancer mortality. Hyaluronan and its receptor, cluster of differentiation (CD)44, have been considered to be valid targets for treating cancer. The anti-CD44 monoclonal antibody IM7 is effective in treating ovarian cancer; however, its toxicity should not be ignored. The present study has developed a new drug carrier system composed of chitosan nano-particles coated with polylactic acid (PLA) to improve the treatment efficacy and reduce toxicity. An ionic crosslinking method and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide were used to prepare the IM7 antibody, which was loaded with chitosan nano-particles. The surfaces of the nano-particles were coated with PLA to generate PLA-chitosan-IM7. Subsequently, transmission electron microscopy (TEM) was used to observe the size and zeta potential of the nano-particles. In addition, a spectrophotometer was used to calculate the loading rate and release rate of the nano-particles in acidic and neutral environments. MTT assay was used to evaluate the anti-proliferative effect of PLA-chitosan-IM7 on the human ovarian cancer cell line HO-8910PM. In addition, anin vivoimaging system was used to further investigate the effect of PLA-chitosan-IM7 on the treatment of mice with ovarian cancer. A total of 35 days subsequent to PLA-chitosan-IM7 treatment, all animals were sacrificed by CO2, and the tumors were removed and weighted. The PLA-chitosan-IM7 nano-particles were successfully prepared, since TEM revealed that their size was 300-400 nm and their zeta potential was +25 mV. According to the spectrophotometry results, the loading rate was 52%, and PLA-chitosan-IM7 exhibited good resistance to acids. MTT assay demonstrated that PLA-chitosan-IM7 could suppress the proliferation of HO-8910PM cellsin vitro. Thein vivoimaging system revealed that PLA-chitosan-IM7 was effective in controlling the development of human ovarian cancer cells and the tumor weight. These results suggest that PLA-chitosan-IM7 could be effective in treating cancersin vitroandin vivo, which may provide a novel approach to enhance the effectiveness of anti-CD44 treatment while reducing its toxicity.
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of PLA, Beijing 100853, P.R. China.
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Laboratory of Applied Molecular Biology, Beijing Institute of Microbiology and Epidemiology, Beijing 100853, P.R. China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of PLA, Beijing 100853, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of PLA, Beijing 100853, P.R. China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of PLA, Beijing 100853, P.R. China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of PLA, Beijing 100853, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
keywords: IM7 antibody; anti-CD44 monoclonal antibody; chitosan nano-particles; ovarian cancer; polylactic acid