Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Liangji Lu, Liyong Jie, Ying Zhou, Jiaojiao Zhang, Tingting Feng, Yue Zhu, Teng Chen, Xiuliang Zhu*, Jiansong Ji* and Zuhua Wang*

Volume 29, Issue 9, 2023

Published on: 27 March, 2023

Page: [686 - 696] Pages: 11

DOI: 10.2174/1381612829666230324091555

Price: $65

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.

« Previous Next »
[1]
Bhattacharya A, Santhoshkumar A, Kurahara H, Harihar S. Metastasis suppressor genes in pancreatic cancer. Pancreas 2021; 50(7): 923-32.
[http://dx.doi.org/10.1097/MPA.0000000000001853] [PMID: 34643607]
[2]
Vetvicka D, Sivak L, Jogdeo CM, et al. Gene silencing delivery systems for the treatment of pancreatic cancer: Where and what to target next? J Control Release 2021; 331: 246-59.
[http://dx.doi.org/10.1016/j.jconrel.2021.01.020] [PMID: 33482273]
[3]
Koujima T, Tazawa H, Hori N, et al. Abstract 3535: A novel tumor-specific oncolytic biological therapy against invasive pancreatic cancer. Cancer Res 2015; 75(15_Supplement): 3535-5.
[http://dx.doi.org/10.1158/1538-7445.AM2015-3535]
[4]
Maeda S, Moore AM, Yohanathan L, et al. Impact of resection margin status on survival in pancreatic cancer patients after neoadjuvant treatment and pancreatoduodenectomy. Surgery 2020; 167(5): 803-11.
[http://dx.doi.org/10.1016/j.surg.2019.12.008] [PMID: 31992444]
[5]
Engberg H, Steding-Jessen M, Øster I, Jensen JW, Fristrup CW, Møller H. Regional and socio-economic variation in survival after a pancreatic cancer diagnosis in Denmark. Dan Med J 2020; 67(2): A08190438.
[PMID: 32053483]
[6]
Matsumoto T, Okabayashi T, Sui K, Morita S, Iwata J, Shimada Y. Preoperative neutrophili-to-lymphocyte ratio is useful for stratifying the prognosis of tumor markers-negative pancreatic cancer patients. Am J Surg 2020; 219(1): 93-8.
[http://dx.doi.org/10.1016/j.amjsurg.2019.04.014] [PMID: 31030989]
[7]
Preuss K, Thach N, Liang X, et al. Using quantitative imaging for personalized medicine in pancreatic cancer: A review of radiomics and deep learning applications. Cancers 2022; 14(7): 1654.
[http://dx.doi.org/10.3390/cancers14071654] [PMID: 35406426]
[8]
Vieira NF, Serafini LN, Novais PC, et al. The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis. Oncotarget 2021; 12(17): 1638-50.
[http://dx.doi.org/10.18632/oncotarget.28038] [PMID: 34434493]
[9]
Dou H, Sun G, Zhang L. CA242 as a biomarker for pancreatic cancer and other diseases. Prog Mol Biol Transl Sci 2019; 162: 229-39.
[http://dx.doi.org/10.1016/bs.pmbts.2018.12.007] [PMID: 30905452]
[10]
Ping C, Wenyuan Y. Application of combined detection of CEA, AFP, CA199 and CA50 in screening for gastrointestinal tumours in healthy individuals. Acta Med Mediter 2019; 35(4): 2179-83.
[11]
Jeon M, Halbert MV, Stephen ZR, Zhang M. Iron oxide nanoparticles as T1 contrast agents for magnetic resonance imaging: Fundamentals, challenges, applications, and prospectives. Adv Mater 2020; 33(23): 1906539.
[PMID: 32495404]
[12]
Zhang J, Jin M, Park YI, Jin L, Quan B. Facile synthesis of ultra-small hollow manganese silicate nanoparticles as pH/GSH-responsive T1-MRI contrast agents. Ceram Int 2020; 46(11): 18632-8.
[http://dx.doi.org/10.1016/j.ceramint.2020.04.175]
[13]
Besenhard MO, Panariello L, Kiefer C, et al. Gavriilidis. Small iron oxide nanoparticles as MRI T-1 contrast agent: Scalable inexpensive water-based synthesis using a flow reactor dagger. Nanoscale 2021; 13(19): 8795-805.
[14]
Park J, Jo S, Lee YM, Saravanakumar G, Kim WJ. Enzyme-triggered disassembly of polymeric micelles by controlled depolymerization via cascade cyclization for anticancer drug delivery. ACS Appl Mater Interfaces 2021; 13(7): 8060-70.
[http://dx.doi.org/10.1021/acsami.0c22644]
[15]
Zhu X, Lu N, Zhou Y, et al. Targeting pancreatic cancer cells with peptide-functionalized polymeric magnetic nanoparticles. Int J Mol Sci 2019; 20(12): 2988.
[http://dx.doi.org/10.3390/ijms20122988] [PMID: 31248076]
[16]
Ghosh B, Biswas S. Polymeric micelles in cancer therapy: State of the art. J Control Release 2021; 332(6): 127-47.
[http://dx.doi.org/10.1016/j.jconrel.2021.02.016] [PMID: 33609621]
[17]
Matsumura Y. Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev 2011; 63(3): 184-92.
[http://dx.doi.org/10.1016/j.addr.2010.05.008] [PMID: 20561951]
[18]
Ahmad H, Arya A, Agrawal S, Dwivedi AK. Chapter 6 - PLGA scaffolds: Building blocks for new age therapeutics.Materials for Biomedical Engineering. 2019; pp. 155-201.
[19]
Silva LM, Hill LE, Figueiredo E, Gomes CL. Delivery of phytochemicals of tropical fruit by-products using poly (dl-lactide-co-glycolide) (PLGA) nanoparticles: Synthesis, characterization, and antimicrobial activity. Food Chem 2014; 165: 362-70.
[http://dx.doi.org/10.1016/j.foodchem.2014.05.118] [PMID: 25038688]
[20]
Mares AG, Pacassoni G, Marti JS, Pujals S, Albertazzi L. Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology. PLoS One 2021; 16(6): e0251821.
[http://dx.doi.org/10.1371/journal.pone.0251821] [PMID: 34143792]
[21]
Liu J, Chen H, Zheng G, et al. Functionalized PLGA-PEG nanoparticles conjugated with aptamer for targeting circulating tumor cells for drug delivery. Nanomedicine 2016; 12(2): 508-9.
[http://dx.doi.org/10.1016/j.nano.2015.12.176]
[22]
Zhang X, Zeng X, Liang X, et al. The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug. Biomaterials 2014; 35(33): 9144-54.
[http://dx.doi.org/10.1016/j.biomaterials.2014.07.028] [PMID: 25109439]
[23]
Paulino da Silva Filho O, Ali M, Nabbefeld R, et al. A comparison of acyl-moieties for noncovalent functionalization of PLGA and PEG-PLGA nanoparticles with a cell-penetrating peptide. RSC Advances 2021; 11(57): 36116-24.
[http://dx.doi.org/10.1039/D1RA05871A] [PMID: 35492790]
[24]
Valetti S, Maione F, Mura S, et al. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor. J Control Release 2014; 192: 29-39.
[http://dx.doi.org/10.1016/j.jconrel.2014.06.039] [PMID: 24984010]
[25]
Valetti S, Mura S, Noiray M, et al. Peptide conjugation: Before or after nanoparticle formation? Bioconjug Chem 2014; 25(11): 1971-83.
[http://dx.doi.org/10.1021/bc5003423] [PMID: 25313527]
[26]
Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B Biointerfaces 2005; 45(3-4): 167-73.
[http://dx.doi.org/10.1016/j.colsurfb.2005.08.005] [PMID: 16198092]
[27]
Wang Z, Sun J, Qiu Y, et al. Specific photothermal therapy to the tumors with high EphB4 receptor expression. Biomaterials 2015; 68: 32-41.
[http://dx.doi.org/10.1016/j.biomaterials.2015.07.058] [PMID: 26264644]
[28]
Kim KS, Park W, Hu J, Bae YH, Na K. A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle. Biomaterials 2014; 35(1): 337-43.
[http://dx.doi.org/10.1016/j.biomaterials.2013.10.004] [PMID: 24139764]
[29]
Popescu Din IM, Balas M, Hermenean A, et al. Novel polymeric micelles-coated magnetic nanoparticles for in vivo bioimaging of liver: Toxicological profile and contrast enhancement. Materials 2020; 13(12): 2722.
[http://dx.doi.org/10.3390/ma13122722] [PMID: 32549296]
[30]
Fei Z, Yoosefian M. Design and development of polymeric micelles as nanocarriers for anti-cancer Ribociclib drug. J Mol Liq 2021; 329(23): 115574.
[http://dx.doi.org/10.1016/j.molliq.2021.115574]
[31]
Lumachi F, Ubiali P, Tozzoli R, Del Conte A, Basso SMM. Serum tumor markers carcinoma antigen (CA) 72-4 versus carcinoembryonic antigen (CEA) in patients with early stage (IA-IB) gastric cancer. Eur J Cancer 2017; 72: S74.
[http://dx.doi.org/10.1016/S0959-8049(17)30321-0]
[32]
Wu B, Deng K, Lu ST, et al. Reduction-active Fe3O4-loaded micelles with aggregation-enhanced MRI contrast for differential diagnosis of Neroglioma. Biomaterials 2021; 268: 120531.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120531] [PMID: 33253964]
[33]
Zhang P, Wang Z, Wang Y, et al. An MRI contrast agent based on a zwitterionic metal-chelating polymer for hepatorenal angiography and tumor imaging. J Mater Chem B Mater Biol Med 2020; 8(31): 6956-63.
[http://dx.doi.org/10.1039/D0TB00893A] [PMID: 32490870]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy