Is tumor cell specificity distinct from tumor selectivity in vivo?A quantitative NIR molecular imaging analysis of nanoliposome targeting
作者机构：Wellman Center for PhotomedicineMassachusetts General Hospital and Harvard Medical SchoolBostonMA02114USA Department of BioengineeringUniversity of Texas at DallasRichardsonTX75080USA Thayer School of EngineeringDartmouth CollegeHanoverNH037551USA Armour College of EngineeringIllinois Institute of TechnologyChicagoIL60616USA Division of Health Sciences and TechnologyHarvard University and Massachusetts Institute of TechnologyCambridgeMA02139USA
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2021年第14卷第5期
页 面：1344-1354页
核心收录：
学科分类：1002[医学-临床医学] 0808[工学-电气工程] 0809[工学-电子科学与技术（可授工学、理学学位）] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学] 0702[理学-物理学]
基 金：This work was supported by the National Institutes of Health(Nos.K99CA215301 and R00CA215301 to G.O.,No.R37CA212187 to K.S.,and Nos.P01CA084203,R01CA156177,R01CA160998,S10ODO1232601,and R21CA220143 to T.H.) the Bullock-Wellman Fellowship(G.O.),Science Foundation Ireland and the Irish Research Council(S.C.),the American Society of Lasers in Surgery and Medicine Research Grant(S.M.).
主 题：molecular recognition receptors nanoparticles specificity cancer
摘 要：The significance and ability for receptor targeted nanoliposomes(tNLs)to bind to their molecular targets in solid tumors in vivo has been questioned,particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity.This study presents,for the first time,in situ near-infrared(NIR)molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors,as opposed to tumor selectivity,which includes influences of enhanced tumor permeability and retention.Results show that neither tumor delivery nor selectivity(tumor-to-normal ratio)of cetuximab and IRDye conjugated tNLs correlate with epidermal growth factor receptor(EGFR)expression in U251,U87,and 9L tumors,and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%.Conversely,their in vivo specificity,which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging,correlates positively with EGFR expression levels in vitro and ex vivo(Pearson’s r=0.92 and 0.96,respectively).This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity.The findings encourage their continued adoption as platforms for precision medicine,and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.
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