Renal Clearable H-Dots Leveraging Ligand Complexation for Enhanced Active Tumor Targeting

IF 11.1 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Yanan Cui, Seung Hun Park, Wesley R. Stiles, Atsushi Yamashita, Jason Dihn, Richard S. Kim, Yadong Zhang, Xiaoran Yin, Yoonji Baek, Haoran Wang, Kai Bao, Homan Kang, Hak Soo Choi
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引用次数: 0

Abstract

The use of ligand conjugation onto nanoparticle surfaces as an active targeting strategy has gained significant attention in the pursuit of improving tumor-specific delivery and retention. However, the chemical conjugation of targeting moieties often induces alterations in the physicochemical properties of nanoparticles, including size, conformation, charge-to-mass ratio, and hydrophilicity/lipophilicity, resulting in unexpected biodistribution and pharmacokinetic profiles. Here, the enhanced active targeting efficiency achieved by integrating cyclic arginine–glycine–aspartic acid (cRGD) peptides onto ultrasmall nanocarrier H-dot while preserving its essential physicochemical and pharmacokinetic attributes is investigated. The resulting cRGD/H-dots demonstrate improved cellular uptake via integrin αvβ3 receptors, accompanied by negligible cytotoxicity. Notably, the active targeting efficacy of cRGD/H-dots compared to unmodified H-dots (1.2%ID/g, two-fold increase) is quantitatively evaluated, validated through fluorescence imaging and histological analysis. The findings highlight that cRGD/H-dots offer enhanced tumor targetability and prolonged tumoral retention while maintaining active renal clearance of unbound molecules.

Abstract Image

利用配体络合增强肿瘤靶向活性的肾脏可清除 H-Dots
将配体缀合到纳米粒子表面作为一种主动靶向策略,在改善肿瘤特异性递送和保留的过程中获得了极大关注。然而,靶向分子的化学共轭往往会导致纳米粒子的理化性质发生改变,包括尺寸、构象、电荷质量比和亲水性/亲油性,从而导致意想不到的生物分布和药代动力学特征。本文研究了将环精氨酸-甘氨酸-天冬氨酸(cRGD)多肽整合到超小型纳米载体 H-dot 上,在保留其基本物理化学和药代动力学特性的同时提高其活性靶向效率。研究结果表明,cRGD/H-点通过整合素αvβ3受体提高了细胞吸收率,同时细胞毒性可忽略不计。值得注意的是,与未修饰的 H-点相比,cRGD/H-点的主动靶向功效得到了定量评估(1.2%ID/g,增加了两倍),并通过荧光成像和组织学分析进行了验证。研究结果表明,cRGD/H-dots 可增强肿瘤靶向性,延长肿瘤保留时间,同时保持未结合分子在肾脏的主动清除。
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来源期刊
CiteScore
14.00
自引率
2.40%
发文量
0
期刊介绍: Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.
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