Preparation and Application of a Bioorganic Nanoparticle-Enhanced PDL1-Targeted Small-Molecule Probe

Abstract

Programmed death ligand 1 (PDL1) is a specific molecular target for the diagnosis and immunotherapy of solid tumors. PET imaging can be used for noninvasive assessments of PDL1 expression in tumors to aid in therapy selection. The most frequently reported small-molecule radiotracer of PDL1 is limited by low imaging specificity, short residence time, and singular functionality. Here, we combined a biocompatible melanin nanoprobe with the PDL1-binding peptide WL12 to construct a novel radiotracer, 124I-WPMN, to enhance PDL1 targeting. The radiochemical purity of 124I-WPMN was >95%, and uptake in A549PDL1 cells was 1.49 ± 0.08% at 2 h. The uptake was blocked by WL12 (0.39 ± 0.03%, P < 0.0001). This novel radiotracer showed a higher affinity for PDL1 (K d = 18.5 nM) than 68Ga-NOTA-WL12 (K d = 24.0 nM). Micro-PET/CT imaging demonstrated specific uptake and a high signal-to-noise ratio in an A549PDL1 xenograft mouse model with a tumor-to-muscle ratio of 27.31 ± 7.03 at 2 h. The levels increased or remained steady for more than 72 h, and tumor uptake was significantly higher than 68Ga-NOTA-WL12, at 6.08 ± 0.62 at 2 h. Prolonged retention of 124I-WPMN makes it possible to conduct PET/MRI imaging over long periods and to perform various imaging techniques. A clear advantage of 124I-WPMN over 68Ga-NOTA-WL12 was observed for PDL1-targeted PET imaging after nanoparticle modification, supporting the utility of 124I-WPMN PET imaging as an effective diagnostic tool for optimizing PDL1-targeted therapies.

Construction and Application of a PD-L1-Targeted Multimodal Diagnostic and Dual-Functional Theranostics Nanoprobe

“… 21 Our previous study had attempted to use organic melanin nanoparticles carrying WL12-SH (WL12 peptide modified with mercaptopropionic acid) peptide to construct a targeted enhanced PET imaging probe, which showed better targeting effects than small molecule probes, while also exhibiting long retention time at the tumor site, providing a reference for subsequent targeted tumor research. 22 Additionally, PET/MRI have achieved great value in the diagnosis of malignant tumors as a new type of nuclear medicine equipment. 23 , 24 But only PET/MRI diagnosis cannot replace contrast-enhanced imaging.…”

“…During this period, we leveraged the high compatibility of melanin nanoparticles to construct a broadly applicable PD-L1-targeted probe for PET/MRI dual-modality enhancement, which is feasible and will benefit more patients. 22 …”

Hyaluronic Acid-Conjugated Fluorescent Probe-Shielded Polydopamine Nanomedicines for Targeted Imaging and Chemotherapy of Bladder Cancer

“…The development of nanotechnology provides new opportunities for the diagnosis and treatment of tumors in recent years . Nanocarriers have advantages in many aspects, such as high drug loading efficiency, increased drug solubility, reduced drug toxicity, biological imaging, etc .…”