摘要
Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody.Here,a molecular engineering technique was used for sitespecific conjugation of antibodies to nanoparticles.We designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 cys.The activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer cells.High binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy.Consistent with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases.Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.
基金
funded by grants from the Global Core Research Center(GCRC,Grant No.2011-0030001)of the National Research Foundation(NRF),Ministry of Science and ICT(MSIT),Republic of Korea
the MSIT,Republic of Korea(NRF-2018R1A2A1A05019203
NRF-2018R1A5A2024425)
the Korean Health Technology R&D Project(No.HI19C0664),Ministry of Health&Welfare,Republic of Korea
作者简介
Hobin Yang,These authors made equal contributions to this work;Quoc-Viet Le,These authors made equal contributions to this work;Corresponding authors:Gayong Shim,E-mail addresses:shimg@snu.ac.kr;Corresponding authors:Yu-Kyoung Oh,E-mail addresses:ohyk@snu.ac.kr;Corresponding authors:Young Kee Shin,E-mail addresses:ykeeshin@snu.ac.kr.
