journal article·2025-01-14

Framework Nucleic Acid-Nanobody Fusion Probe-Based Pharmacokinetics Modulation and Analysis for Efficient Positron Emission Tomography Imaging

Yani Yang, Zhiqiang Ren, Dan Wang, Decui Tang, Weijun Wei, Shaoli Song, Yifan Lyu, Ding Ding, Weihong Tan

ACS Nano· Volume 19· Issue 1
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Abstract

Nanobodies are promising for immunoPET imaging due to their excellent antigen recognition and tumor targeting, yet rapid clearance limits their tumor accumulation. Although multimerization and albumin binding can extend their circulation time and improve tumor targeting, a simple and universal method for creating protein multimers is still needed. Here, we leveraged the facile synthesis, controllable size, and precise assembly of DNA nanotechnology to construct CD47-targeted framework nucleic acid-nanobody fusion probes with multiple valences and sizes. Following comprehensive structural characterization, in vitro specificity assessment and in vivo PET/CT imaging analysis were conducted on a colorectal cancer LS174T mouse model. Furthermore, a pharmacokinetic model was developed and fitted with considerable in vivo data to prove its rationality, followed by testing the effects on tumor uptake prediction by changing different pharmacokinetic parameters. Indeed, by manipulating the size of the nucleic acid scaffolding and the number of attached nanobodies, we could precisely modulate the accumulation of probes at the tumor site. Overall, this study not only developed an efficient strategy for constructing nanobody multimers but also provided a pharmacokinetic model, allowing profound insight into the multidimensional data obtained experimentally and informing the design of future imaging probes with predictable delivery efficacies.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Monoclonal and Polyclonal Antibodies Research · Advanced biosensing and bioanalysis techniques · Bacteriophages and microbial interactions

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

Affiliations

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China

Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China

Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China

Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China

Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China

Furong Laboratory, Changsha, Hunan 410082, China

Funding

Natural Science Foundation of Hunan Province · National Key Research and Development Program of China · Innovative Research Team of High-level Local University in Shanghai · Science and Technology Commission of Shanghai Municipality · Fundamental Research Funds for the Central Universities · Science and Technology Program of Hunan Province · National Natural Science Foundation of China · Scientific Research Program of FuRong Laboratory

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