Renal Clearable H-Dots Leveraging Ligand Complexation for Enhanced Active Tumor Targeting
Yanan Cui
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
School of Pharmacy, Jining Medical College, Rizhao, Shandong, 276826 China
Search for more papers by this authorSeung Hun Park
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorWesley R. Stiles
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorAtsushi Yamashita
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorJason Dinh
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorRichard S. Kim
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorYadong Zhang
School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250021 China
Search for more papers by this authorXiaoran Yin
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Department of Oncology, The Second Affiliate Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, 710004 China
Search for more papers by this authorYoonji Baek
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorHaoran Wang
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorKai Bao
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorCorresponding Author
Homan Kang
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorCorresponding Author
Hak Soo Choi
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorYanan Cui
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
School of Pharmacy, Jining Medical College, Rizhao, Shandong, 276826 China
Search for more papers by this authorSeung Hun Park
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorWesley R. Stiles
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorAtsushi Yamashita
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorJason Dinh
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorRichard S. Kim
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorYadong Zhang
School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250021 China
Search for more papers by this authorXiaoran Yin
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Department of Oncology, The Second Affiliate Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, 710004 China
Search for more papers by this authorYoonji Baek
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorHaoran Wang
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorKai Bao
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorCorresponding Author
Homan Kang
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorCorresponding Author
Hak Soo Choi
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
Search for more papers by this authorAbstract
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.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
|---|---|
| smsc202400246-sup-0001-SuppData-S1.pdf1.3 MB | Supplementary Material |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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