Zhong Wan1, Fangyuan Xie2, Liang Wang3, Guoqing Zhang2, Hai Zhang3. 1. Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China. 2. Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China. 3. Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, People's Republic of China.
Abstract
PURPOSE: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment. METHODS: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo. RESULTS: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile. CONCLUSION: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.
PURPOSE: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment. METHODS: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo. RESULTS: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile. CONCLUSION: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.
Authors: Zhijian He; Anita Schulz; Xiaomeng Wan; Joshua Seitz; Herdis Bludau; Daria Y Alakhova; David B Darr; Charles M Perou; Rainer Jordan; Iwao Ojima; Alexander V Kabanov; Robert Luxenhofer Journal: J Control Release Date: 2015-02-26 Impact factor: 9.776
Authors: Stéphane Oudard; Karim Fizazi; Lisa Sengeløv; Gedske Daugaard; Fred Saad; Steinbjørn Hansen; Marie Hjälm-Eriksson; Jacek Jassem; Antoine Thiery-Vuillemin; Orazio Caffo; Daniel Castellano; Paul N Mainwaring; John Bernard; Liji Shen; Mustapha Chadjaa; Oliver Sartor Journal: J Clin Oncol Date: 2017-07-28 Impact factor: 44.544