The gastrin-releasing peptide receptor (GRPR) is highly expressed in various malignant tumors (e.g., glioblastoma, prostate cancer, and breast cancer) and has emerged as an important molecular target for precision cancer diagnosis and therapy. In recent years, the combined application of radionuclide-labeled GRPR ligands with positron emission tomography/computed tomography (PET/CT) has achieved groundbreaking progress in noninvasive diagnosis, accurate staging, and therapeutic monitoring of GRPR-positive tumors. Meanwhile, GRPR-targeted radionuclide therapeutics have demonstrated significant therapeutic potential and promising clinical applications in trials. This GRPR-based theranostic strategy pioneers a novel approach for precision medicine in GRPR-overexpressing tumors.

The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic. Herein, we proposed a tumor-derived extracellular vesicle (EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles (DCNPs) with strong near infrared II (NIR-II) luminescence at 1,525 nm. The EVs were metabolically engineered with azide group, followed by in vivo labeling of DCNPs through copper-free click chemistry. By taking advantage of the homologous targeting property of tumor derived EVs, remarkable improvement in the tumor accumulation (6.5% injection dose (ID)/g) was achieved in the subcutaneous colorectal cancer model when compared to that of individual DCNPs via passive targeting (1.1% ID/g). Importantly, such bioorthogonal labeling significantly increased NIR-II luminescence signals and prolonged the retention at tumor sites. Our work demonstrates the great potential of EVs-mediated bioorthogonal approach for in vivo labeling of NIR-II optical probes, which provides a robust tool for tumor-specific imaging and targeted therapy.

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer (TNBC) due to its relatively low response to traditional therapeutics. The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity, resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment. To address these limitations, here we developed a robust pyroelectric BaTiO₃@Au core–shell nanostructure (BTO@Au) to selectively and persistently block energy generation of tumor cells. Stimulated by near-infrared (NIR) laser, the Au shell could generate heat to activate the BaTiO₃ core to produce reactive oxygen species (ROS) regardless of the constrained microenvironment, thus prominently inhibits mitochondrial oxidative phosphorylation (OXPHOS) and reduces ATP production to induce TNBC cell apoptosis. The therapeutic effects have been well demonstrated in vitro and in vivo, paving a new way for the development of metabolic interventions.

Peptide receptor radionuclide therapy (PRRT) specifically uses radiolabeled peptides as biological targeting vectors designed to deliver cytotoxic levels of radiation dose to cancer cells that overexpress specific receptors. In recent years, how to further improve the efficacy of radiotherapeutic drugs for PRRT has been an international research hotspot.The peptides with Evans blue motif, uses endogenous albumin as a reversible carrier to effectively extend the half-life in the blood and substantially increase targeted accumulation and retention within the tumor to achieve better efficacy. This review focuses on the clinical translational research of Evans blue modified peptides used for theranostics.