Preparation and Characterization of PLGA-based Magnetic Polymer Nanoparticles for Targeting Pancreatic Adenocarcinoma.

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.

• Authors: Liangji Lu, Liyong Jie, Ying Zhou, Jiaojiao Zhang, Tingting Feng, Yue Zhu, Teng Chen, Xiuliang Zhu, Jiansong Ji, Zuhua Wang
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 29 Issue 9 Pg. 686-696 ( 2023) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 36967466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• polyethylene glycol-poly(lactide-co-glycolide)
• Polymers
• Magnetite Nanoparticles
• Contrast Media
• Polyethylene Glycols
• Peptides

Topics

• Humans
• Adenocarcinoma
• Polymers
• Pancreatic Neoplasms (diagnostic imaging, drug therapy)
• Cell Line, Tumor
• Magnetite Nanoparticles (chemistry)
• Contrast Media (chemistry)
• Polyethylene Glycols (chemistry)
• Magnetic Resonance Imaging (methods)
• Peptides
• Nanoparticles