Visual targeted therapy of hepatic cancer using homing peptide modified calcium phosphate nanoparticles loading doxorubicin guided by T1 weighted MRI

• Published in: Nanomedicine 2018-10, Vol.14 (7), p.2167-2178
• Main Authors: Zhang, Nan-nan, Yu, Ri-sheng, Xu, Min, Cheng, Xing-yao, Chen, Chun-miao, Xu, Xiao-ling, Lu, Chen-ying, Lu, Kong-jun, Chen, Min-jiang, Zhu, Meng-lu, Weng, Qiao-you, Hui, Jun-guo, Zhang, Qian, Du, Yong-Zhong, Ji, Jian-song
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Apoptosis - drug effects; Calcium phosphate nanoparticles; Calcium Phosphates - chemistry; Cell Proliferation - drug effects; Contrast Media; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Female; Gadolinium; Gadolinium DTPA - chemistry; Hepatic cancer; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Magnetic resonance imaging (MRI); Magnetic Resonance Imaging - methods; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Targeted Therapy; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Peptide Fragments - chemistry; pH-sensitivity; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.06.014

Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02 mM−1 s−1) than commercial MR contrast agent Gd-DTPA (3.3765 mM−1 s−1). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment. A novel pH-sensitivity multifunctional calcium phosphate nanoparticles, modified by hepatocarcinoma cells' specific binding polypeptide A54 peptide, loaded with MR contrast agent Gd-DTPA and antitumor drug DOX (A54-CaP/Gd-DTPA/DOX) was successfully designed for T1-weighted MR imaging guiding targeting hepatic cancer therapy. [Display omitted]