Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Jul 27

PMID 35890353

Authors

Son Long Ho

Huan Yue

Sangyeol Lee

Tirusew Tegafaw

Mohammad Yaseen Ahmad

Shuwen Liu

Abdullah Khamis Ali Al Saidi

Dejun Zhao

Ying Liu

Sung-Wook Nam

Kwon Seok Chae

Yongmin Chang

Gang Ho Lee

Affiliations

Soon will be listed here.

Abstract

Hydrophilic and biocompatible PAA-coated ultrasmall GdO nanoparticles (d = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-GdO and cRGD/FA-PAA-GdO nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T magnetic resonance imaging (MRI). cRGD/FA-PAA-GdO nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-GdO nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-GdO nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-GdO nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-GdO nanoparticles, which prolonged their circulation in the blood.

Citing Articles

Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment.

Cecchi D, Jackson N, Beckham W, Chithrani D Pharmaceutics. 2024; 16(2).

PMID: 38399237 PMC: 10891984. DOI: 10.3390/pharmaceutics16020175.

In situ cellular hitchhiking of nanoparticles for drug delivery.

Udofa E, Zhao Z Adv Drug Deliv Rev. 2023; 204:115143.

PMID: 38008185 PMC: 10841869. DOI: 10.1016/j.addr.2023.115143.

References

Nie S . Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine (Lond). 2010; 5(4):523-8. PMC: 2913868. DOI: 10.2217/nnm.10.23. View

Bridot J, Faure A, Laurent S, Riviere C, Billotey C, Hiba B . Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. J Am Chem Soc. 2007; 129(16):5076-84. DOI: 10.1021/ja068356j. View

Mohammadinejad R, Moosavi M, Tavakol S, Ozkan Vardar D, Hosseini A, Rahmati M . Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy. 2018; 15(1):4-33. PMC: 6287681. DOI: 10.1080/15548627.2018.1509171. View

Owens 3rd D, Peppas N . Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2005; 307(1):93-102. DOI: 10.1016/j.ijpharm.2005.10.010. View

Zou Y, Wei Y, Sun Y, Bao J, Yao F, Li Z . Cyclic RGD-Functionalized and Disulfide-Crosslinked Iodine-Rich Polymersomes as a Robust and Smart Theranostic Agent for Targeted CT Imaging and Chemotherapy of Tumor. Theranostics. 2019; 9(26):8061-8072. PMC: 6857068. DOI: 10.7150/thno.37184. View

Gagliardini E, Conti S, Benigni A, Remuzzi G, Remuzzi A . Imaging of the porous ultrastructure of the glomerular epithelial filtration slit. J Am Soc Nephrol. 2010; 21(12):2081-9. PMC: 3014021. DOI: 10.1681/ASN.2010020199. View

Choi H, Liu W, Misra P, Tanaka E, Zimmer J, Ipe B . Renal clearance of quantum dots. Nat Biotechnol. 2007; 25(10):1165-70. PMC: 2702539. DOI: 10.1038/nbt1340. View

Kattel K, Park J, Xu W, Kim H, Lee E, Bony B . A facile synthesis, in vitro and in vivo MR studies of d-glucuronic acid-coated ultrasmall Ln₂O₃ (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential MRI contrast agent. ACS Appl Mater Interfaces. 2011; 3(9):3325-34. DOI: 10.1021/am200437r. View

Saul J, Annapragada A, Natarajan J, Bellamkonda R . Controlled targeting of liposomal doxorubicin via the folate receptor in vitro. J Control Release. 2003; 92(1-2):49-67. DOI: 10.1016/s0168-3659(03)00295-5. View

10.

Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H . Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. J Control Release. 2011; 153(2):141-8. DOI: 10.1016/j.jconrel.2011.03.012. View

11.

Massoud T, Gambhir S . Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003; 17(5):545-80. DOI: 10.1101/gad.1047403. View

12.

Benoit D, Zhu H, Lilierose M, Verm R, Ali N, Morrison A . Measuring the grafting density of nanoparticles in solution by analytical ultracentrifugation and total organic carbon analysis. Anal Chem. 2012; 84(21):9238-45. PMC: 4538977. DOI: 10.1021/ac301980a. View

13.

Tang Y, Wang X, Li J, Nie Y, Liao G, Yu Y . Overcoming the Reticuloendothelial System Barrier to Drug Delivery with a "Don't-Eat-Us" Strategy. ACS Nano. 2019; 13(11):13015-13026. DOI: 10.1021/acsnano.9b05679. View

14.

Yoo J, Chambers E, Mitragotri S . Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Curr Pharm Des. 2010; 16(21):2298-307. DOI: 10.2174/138161210791920496. View

15.

Ho S, Yue H, Tegafaw T, Ahmad M, Liu S, Nam S . Gadolinium Neutron Capture Therapy (GdNCT) Agents from Molecular to Nano: Current Status and Perspectives. ACS Omega. 2022; 7(3):2533-2553. PMC: 8793081. DOI: 10.1021/acsomega.1c06603. View

16.

Wahsner J, Gale E, Rodriguez-Rodriguez A, Caravan P . Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers. Chem Rev. 2018; 119(2):957-1057. PMC: 6516866. DOI: 10.1021/acs.chemrev.8b00363. View

17.

Angelopoulou A, Kolokithas-Ntoukas A, Fytas C, Avgoustakis K . Folic Acid-Functionalized, Condensed Magnetic Nanoparticles for Targeted Delivery of Doxorubicin to Tumor Cancer Cells Overexpressing the Folate Receptor. ACS Omega. 2020; 4(26):22214-22227. PMC: 6933766. DOI: 10.1021/acsomega.9b03594. View

18.

Yong K, Roy I, Law W, Hu R . Synthesis of cRGD-peptide conjugated near-infrared CdTe/ZnSe core-shell quantum dots for in vivo cancer targeting and imaging. Chem Commun (Camb). 2010; 46(38):7136-8. DOI: 10.1039/c0cc00667j. View

19.

Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H . Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 2005; 40(11):715-24. DOI: 10.1097/01.rli.0000184756.66360.d3. View

20.

Akhtar M, Ahamed M, Alhadlaq H, Alrokayan S . Toxicity Mechanism of Gadolinium Oxide Nanoparticles and Gadolinium Ions in Human Breast Cancer Cells. Curr Drug Metab. 2019; 20(11):907-917. DOI: 10.2174/1389200220666191105113754. View