DataVXACS NanoPaper
journal article·2025-01-28

Preclinical and First-in-Human Study of a Compact Radionuclide Labeled Self-Assembly Nanomedicine for Chemo-Radio-Theranostics of Cancer

Hehe Xiong, Rongxi Wang, Heng Zhang, Qianyu Zhang, Yatong Qin, Chao Du, Xinyi Zhang, Jinmin Ye, Changrong Shi, Huaxiang Shen, Zhaohui Zhu, Zijian Zhou, Xiaoyuan Chen, Jingjing Zhang

ACS Nano· Volume 19· Issue 3
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Source abstract

Abstract

The emerging combination of chemotherapy and radionuclide therapy has been actively investigated to overcome the limitations of monotherapy and augment therapeutic efficacy. However, it remains a challenge to design a single delivery vehicle that can incorporate chemotherapeutics and radionuclides into a compact structure. Here, a chelator DOTA- or NOTA-modified Evans blue conjugated camptothecin molecule (EB-CPT) nanoprodrug was synthesized, which could self-assemble into nanoparticles due to its inherent amphiphilicity. The nanoparticles could then be effectively labeled with therapeutic radionuclide lutetium-177 ( 177 Lu) or diagnostic radionuclides gallium-68 ( 68 Ga)/copper-64 ( 64 Cu) with high radiolabeling efficiency and radiochemical stability. Impressively, a single-dose chemoradiation therapy of [ 177 Lu]Lu-DOTA-EB-CPT plus EB-CPT effectively inhibited tumor growth in HCT116 tumor-bearing mice compared to the respective individual therapeutic approach. The [ 64 Cu]Cu-NOTA-EB-CPT nanoparticles also exhibited excellent in vivo characteristics including favorable blood circulation properties and prolonged tumor retention in tumor-bearing mice. The safety, feasibility, tolerability, and biodistribution of [ 68 Ga]Ga-NOTA-EB-ss-CPT were also preliminarily characterized in a first-in-human study. This study presents a simple but robust EB-CPT radiopharmaceutical that leverages EB as an albumin binder to strike a delicate balance between enhanced tumor accumulation, safety, and diagnostic efficacy, facilitating an integrated theranostic strategy within a single molecular structure. This radionuclide-labeled EB-CPT nanomedicine presents a step toward clinical translation of the combination of chemotherapy and radiotheranostics.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Radiopharmaceutical Chemistry and Applications · Nanoparticle-Based Drug Delivery · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen 361102, China

Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China

Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore

Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, 11 Biopolis Way, Helios, 138667, Singapore

Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore

Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, 117575 Singapore

Funding

National Medical Research Council · Ministry of Education - Singapore · China Postdoctoral Science Foundation · Natural Science Foundation of Fujian Province · National Research Foundation Singapore · Science, Technology and Innovation Commission of Shenzhen Municipality · National University of Singapore · National Natural Science Foundation of China · Xiamen University · Fujian Province

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