期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 17, 页码 15212-15221出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b21679
关键词
dendrimers; gold nanoparticles; RGD peptide; zwitterions; dual mode CT/MR imaging; lung cancer metastasis
资金
- National Natural Science Foundation of China [21773026, 81761148028]
- Science and Technology Commission of Shanghai Municipality [17540712000, 18520750400]
- Program of Shanghai Academic Reseach Leader [19XD1400100]
- FCT-Fundacao para a Ciencia e a Tecnologia [PEst-OE/QUI/UI0674/2019]
- project PROEQUIPRAM - Reforco do Investimento em Equipamentos e Infraestruturas Cientificas na RAM [M1420-01-0145-FEDER-000008]
- ARDITI-Agencia Regional para o Desenvolvimento da Investigacao Tecnologia e Inovacao [M1420-01-0145-FEDER-000005, Madeira 14-20]
Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 +/- 0.9 mV display a good X-ray attenuation property, relatively high r(1) relaxivity (13.17 mM s(-1)), acceptable cytocompatibility, and targeting specificity to alpha(v)beta(3) integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.
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