Title:Preparation and Characterization of PLGA-based Magnetic Polymer Nanoparticles
for Targeting Pancreatic Adenocarcinoma
Volume: 29
Issue: 9
Author(s): Liangji Lu, Liyong Jie, Ying Zhou, Jiaojiao Zhang, Tingting Feng, Yue Zhu, Teng Chen, Xiuliang Zhu*, Jiansong Ji*Zuhua Wang*
Affiliation:
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional
Research of Zhejiang Province, School of Medicine, Lishui Hospital, Zhejiaing University, Lishui, Zhejiang, 323000, China
- College
of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China
- Nano-drug Technology Research Center of Guizhou University of
Traditional Chinese Medicine, Guiyang, 550025, China
Keywords:
Pancreatic cancer, early diagnosis, tumor-targeted delivery, magnetic resonance imaging, USPIO, BxPC-3, CKAAKN peptide.
Abstract:
Aims: This study aims to develop a novel tumor-targeted molecular probe for pancreatic cancer imaging.
The objective of this is to prepare a CKAAKN peptide-conjugated poly (lactic-co-glycolic acid)-poly (ethylene
glycol) amphiphilic polymer (CKAAKN-PEG-PLGA) for the tumor-targeted delivery of magnetic resonance
imaging (MRI) contrast agent ultrasmall superparamagnetic iron oxide (USPIO).
Background: The early diagnosis of pancreatic cancer is crucial for improving its prognosis, but the clinical application
of many diagnostic methods is limited owing to a lack of specificity and sensitivity.
Methods: CKAAKN-PEG-PLGA was synthesized by the amidation reaction. USPIO-loaded polymeric magnetic
nanoparticles (USPIO@CKAAKN-PEG-PLGA) were prepared by the emulsion solvent evaporation method.
The in vitro tumor targeting and bio-safety of nanoparticles were evaluated by targeted cellular uptake, MR
imaging and MTT assay.
Results: USPIO@CKAAKN-PEG-PLGA nanoparticles showed excellent biosafety with an average diameter
of 104.5 ± 4.1 nm. Modification of CKAAKN peptide could improve USPIO binding ability to internalize into
CKAAKN-positive BxPC-3 cells compared with non-targeting nanoparticles and the control group. The relative
fluorescence intensity in BxPC-3 and HPDE6-C7 cells was 23.77 ± 4.18 and 6.44 ± 2.10 (p < 0.01), and respectively
became 16.13 ± 0.83 and 11.74 ± 1.74 after the addition of free CKAAKN peptide. In vitro MR
imaging studies showed that an obvious decrease in the signal intensity was observed in the targeted nanoparticles
group incubated with BxPC-3 and HPDE6-C7 cells (p < 0.05).
Conclusion: USPIO@CKAAKN-PEG-PLGA nanoparticles could significantly enhance the tumor specificity
of USPIO in CKAAKN-positive pancreatic cancer cell BxPC-3, which is expected as a promising candidate of
MRI contrast enhancement for the early diagnosis of pancreatic cancer.
