Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro

// Jing Ma 1, 2, 3, * , Ming Shen 4, * , Chang Song Xu 5, * , Ying Sun 4 , You Rong Duan 4 , Lian Fang Du 2 1 Department of Ultrasound, Songjiang Hospital Affiliated to The First People’s Hospital of Shanghai Jiao tong University, Shanghai 201600, China 2 Department of Ultrasound, Shanghai First People’s Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai 200080, China 3 Department of Ultrasound, Shanghai East Hospital Affiliated to Tong ji University, Shanghai 200120, China 4 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, P. R. China 5 Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu 223001, China * These authors have contributed equally to this work Correspondence to: Lian Fang Du, email: du_lf@163.com You Rong Duan, email: yrduan@shsci.org Keywords: double-targeted, nanoparticles, antitumor, ultrasound contrast enhanced imaging, pancreatic cancer Received: July 25, 2016 Accepted: October 19, 2016 Published: November 09, 2016 ABSTRACT A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro . Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.