Preparation and in vitro evaluation of pancreatic cancer-targeted nano-scale ultrasound contrast agent
10.3724/SP.J.1008.2015.01277
- Author:
Chuling HU
1
Author Information
1. Department of Pharmacy, Changhai Hospital, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Nano-scale ultrasound contract agent;
Pancreatic neoplasms;
Perfluoroctyl bromide;
Polylactiv-co-glycolic acid;
Targeting therapy
- From:
Academic Journal of Second Military Medical University
2015;36(12):1277-1283
- CountryChina
- Language:Chinese
-
Abstract:
Objective To prepare a pancreatic cancer-targeted nano-scale ultrasound contrast agent (T-UCA) and to evaluate its in vitro targeting effect. Methods PLGA-PEG-NHS was synthesized with poly(lactic-co-glycolic acid) (PLGA) , N hydroxysuccinimide (NHS) and polyethylene glycol (PEG). The construction of PLGA-PEG-NHS was characterized by1H NMR. Perfluoroctyl bromide (PFOB) loaded PLGA nanoparticle contrast agent was prepared using emulsion evaporation technique with PLGA-PEG-NHS and PFOB , and the products were further conjugated with Hedgehog antibody. The morphology of T-UCA were characterized by transmission electron microscopy , and the size distribution and Zeta potential of T-UCA were characterized by dynamic light scattering method. Furthermore , the drug entrapment efficiency and loading capacity of T-UCA were determined by OC-MS , and the release rate of T-UCA in vitro was examined by dialysis method. Finally , the in vitro targeting performance was quantitatively verified by fluorescence microscopy and flow cytometry with human pancreatic cancer lines SW1990 and CFPAC-1. Results The average diameter and the Zeta potential of T-UCA were 198. 9 nm and -31. 8 mV, respectively. Moreover , the encapsulation efficiency and drug loading of T-UCA was (63. 7 ± 3. 9) % and (14.3 ± 0.9)% , respectively. Nearly 85. 3% liquid perfluorocarbon was released from the T-UCA within 48 h. In vitro cell experiments showed that the targeted contrast agent could bind to SW1990 cells which had high expression of Hedgehog antigen , while not to the CFPAC-1 cells without expression of Hedgehog antigen Conclusion The emulsion evaporation technique can be used to prepare T-UCA with desirable characteristics, and the prepared T-UCA can specifically cancer cells with high expression of Hedgehog, making it a promising pancreatic cancer-targeted nanosacle ultrasound contrast agent.