About

Weibo Cai is an Affiliate Professor at the School of Pharmacy and a Professor of Radiology at the School of Medicine and Public Health at the University of Wisconsin-Madison. His research focuses on biomedical nanotechnology and molecular imaging, primarily utilizing positron emission tomography and multimodal imaging techniques. He is involved in image-guided drug delivery, theranostics, translational research, tumor targeting, and cancer diagnosis and therapy. Additionally, his work encompasses imaging of cardiovascular diseases and diabetes, contributing to advancements in medical imaging and targeted treatment strategies.

Research topics

• Medicine
• Nanotechnology
• Materials science
• Chemistry
• Internal medicine
• Political Science
• Cancer research
• Pharmacology
• Biochemistry
• Computer Science
• Biology
• Pathology
• Metallurgy
• Intensive care medicine
• Risk analysis (engineering)
• Biotechnology
• Engineering ethics
• Engineering
• Medical physics
• Immunology

Selected publications

• Integrated radio-theranostics using a [ ⁸⁹ Zr]Zr-/[ ¹⁷⁷ Lu]Lu-labeled B7-H3 antibody-drug conjugate for prostate cancer

  Theranostics · 2026-04-16

  articleOpen accessSenior author

  Rationale: Prostate cancer remains a leading cause of cancer-related mortality in men.Although PSMA-directed theranostics have achieved clinical success, heterogeneous expression and therapy-induced downregulation limit their broad applicability.B7-H3 (CD276), which is highly and stably expressed in prostate cancer, represents a promising alternative theranostic target.Methods: A B7-H3 targeted antibody-drug conjugate (ADC) was radiolabeled with [ 89 Zr]Zr-for immunoPET imaging and [ 177 Lu]Lu for radionuclide therapy.In vitro binding specificity, in vivo tumor targeting, biodistribution, therapeutic efficacy, dosimetry, and safety were systematically assessed in prostate cancer xenograft models, with comparisons to radiolabeled antibody, ADC monotherapy, sequential therapy, and vehicle controls.Results: Histological analysis in prostate cancer patients suggested B7-H3 was consistently and highly expressed in primary and metastatic lesions and remained stable under therapeutic intervention.[ 89 Zr]Zr-B7-H3 ADC immunoPET imaging demonstrated high and specific tumor uptake (33.2 1.0 %ID/g at 144 h) and favorable tumor-to-background ratios.Therapeutic studies revealed that [ 177 Lu]Lu-B7-H3 ADC achieved marked tumor growth inhibition and survival benefit, with comparable efficacy even if reduced the dose of ADC in the treatment system.Integrated [ 177 Lu]Lu-ADC therapy outperformed radiolabeled antibody, ADC monotherapy, and sequential treatment strategies.No additional organ toxicity was observed compared with ADC alone, and transient hematological changes following [ 177 Lu]Lu administration were reversible.Conclusions: The [ 89 Zr]Zr-/[ 177 Lu]Lu-B7-H3 ADC theranostic platform enables accurate imaging, precise tumor targeting, and enhanced antitumor efficacy at reduced ADC doses without increasing systemic toxicity, supporting its translational potential for prostate cancer.

  PublisherOA PDFDOI

• DNA Repair Enzyme Regulation Strategy for Enhanced Pancreatic Neuroendocrine Tumor Therapy via Targeting siRNA-Lipid Nanoparticles

  ACS Nano · 2026-04-01

  articleOpen accessCorresponding

  Pancreatic neuroendocrine tumors (panNETs) originate from neuroendocrine cells with high rates of metastasis, rendering many patients ineligible for surgical resection. The first-line chemotherapeutic agent Temozolomide (TMZ) for metastatic panNETs faces challenges related to resistance, primarily mediated by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). This resistance limits the long-term efficacy of TMZ in many patients. To overcome these challenges, we developed the lipid nanoparticles (LNPs) modified with somatostatin receptors (SSTRs) targeting peptide of Octreotide to codeliver the TMZ and MGMT-siRNA (LOTR) to improve the therapeutic efficacy of TMZ via inhibiting MGMT-mediated resistance and also reducing systemic toxicity caused by TMZ. The in vitro and in vivo results demonstrated that the LOTR system significantly sensitized the tumor response to TMZ, lowered drug resistance, and reduced off-target effects, offering a promising approach for the treatment of advanced panNETs.

  PublisherDOI

• A Calixsalan-based ionizable lipid for macrophage-targeted Trem2 siRNA delivery attenuates atherosclerosis

  Biomaterials · 2026-03-17

  articleOpen access
  PublisherOA PDFDOI

• Nanomedicine in immunotherapy of urinary system tumors: advances, synergistic strategies, and translational challenges

  Journal of Nanobiotechnology · 2026-04-07

  articleOpen access

  Urological malignancies impose a substantial global health burden, underscoring the urgent need for more effective therapeutic strategies. Although immunotherapy has transformed cancer management, its benefit in urological tumors remains inconsistent, often limited by tumor-intrinsic resistance and an immunosuppressive tumor microenvironment. In this setting, nanomedicine has emerged as a promising platform that extends beyond conventional drug delivery to actively modulate antitumor immune responses through engineered nano-bio interactions. This review presents a mechanistically organized overview of nanomedicine-enabled immunotherapeutic strategies for urological cancers, focusing on prostate cancer, renal cell carcinoma, and bladder cancer. We examine how advanced nanoplatforms regulate antitumor immunity through targeted delivery, externally activatable photodynamic immunotherapy, tumor immune microenvironment reprogramming, immunotherapy sensitization and combination strategies, and neoantigen-based vaccination. We also discuss key translational barriers-including delivery heterogeneity, biosafety, manufacturing scalability, and patient stratification-and outline design considerations for developing clinically translatable nano-based immunotherapeutic. Overall, this review highlights the potential of nanomedicine to overcome current limitations in cancer immunotherapy and to support the development of more effective, personalized treatments for urological malignancies.

  PublisherDOI

• Synergistic Gene Immunotherapy for Lung Cancer via Targeted Nanomedicine Restoring Genetic Tumor Suppression and Activating STING Pathway

  ACS Nano · 2026-02-12 · 1 citations

  articleOpen accessCorresponding

  Lung cancer, particularly non-small cell lung cancer (NSCLC), presents significant therapeutic challenges due to its high mortality and complex pathogenesis. General strategies, including chemotherapy, immunotherapy, and even novel gene therapy, fail to provide comprehensive inhibition against NSCLC individually. Here, a novel gene-immunotherapeutic nanomedicine, pTMEM163/cGAMP@cRGD-BSA/LDHs (TGR-BLDHs), was developed by employing cyclic Arg-Gly-Asp (cRGD)-modified bovine serum albumin/layered double hydroxide (BSA-LDH) nanoparticles for targeted delivery of TMEM163, a newly identified tumor suppressor gene (TSG) of NSCLC and cGAS/STING agonist (cGAMP). TGR-BLDHs exhibited highly specific NSCLC tumor suppression via desirable tumor-targeted TSG gene therapy. Meanwhile, TGR-BLDHs successfully evoked potent antitumor effects by activating the cGAS/STING pathway in both antigen-presenting and cancerous cells, eventually inhibiting tumor progression in vivo. The current study highlighted the potential of TGR-BLDHs for effective gene immunotherapy against NSCLC with desirable tumor specificity and biocompatibility, offering a promising gene-immunotherapeutic strategy for NSCLC.

  PublisherDOI

• Improved X-ray absorption capability of Core-shell nano-transducer in situ enhances γ-ray-excited radioluminescence imaging in vivo

  Journal of Nanobiotechnology · 2026-01-13

  articleOpen access

  Radioluminescence imaging (RLI) using nanoscintillators offers great potential for biomedical applications, yet remains constrained by low quantum efficiency and the reliance of Cerenkov imaging on high-energy radionuclides. The rational design of core-shell nano-transducers overcomes these constraints by enhancing X-ray absorption and energy confinement, thereby enabling efficient γ-ray excited radioluminescence. We engineered NaGdF₄:15%Eu@NaLuF₄ core-shell nanoparticles as a superior nano-scintillator, designed to leverage Technetium-99m (99mTc) as an ideal excitation source. The key advantage of our system lies in its ability to efficiently convert the low-energy electron emissions from 99mTc into intense radioluminescence, completely bypassing the Cerenkov threshold and thus overcoming the key limitations of Cerenkov radiation. The optimized core-shell structure exhibited a radioluminescence intensity slope (k1) of 10.9 × 104 (p/s/cm2/sr)/MBq under 99mTc excitation, representing a 110% enhancement over the core-only nanoparticles. This enhanced scintillation output was paired with a remarkable CT contrast slope (k₂) of 47.6 HU/(mg/mL), demonstrating superior X-ray absorption capability. Capitalizing on these attributes, when integrated with 99mTc-sulfur colloid, this platform enabled background-free, multimodal SPECT/CT/RLI for high-contrast sentinel lymph node mapping and precise image-guided resection in murine models, the success of which was conclusively confirmed by histology. This work presents a progressive optimization of lanthanide-based nanoparticles (LnNPs) scintillators, unveiling their structure-dependent radioluminescence properties for enhanced output efficiency. It thereby provides key insights into energy transfer processes within core-shell architectures and fundamentally expands the repertoire of applicable radionuclides for optical imaging.

  PublisherDOI

• Enhanced tumor retention and therapeutic potency in radionuclide therapy using GSH-induced self-assembling peptides

  Journal of Controlled Release · 2025-08-08 · 4 citations

  articleOpen accessCorresponding
  PublisherOA PDFDOI

• Targeting Claudin18.2 for cancer theranostics: From molecular imaging to precision therapy

  iScience · 2025-09-02

  reviewOpen access

  Claudin18.2 (CLDN18.2), a specific tight junction protein isoform, is minimally expressed in normal gastric mucosa but aberrantly overexpressed in various cancers. It plays a key role in regulating tumor cell differentiation, proliferation, and migration, making it an attractive therapeutic target, especially in gastric cancer. Moreover, molecular imaging techniques such as immuno-positron emission tomography, immuno-single photon emission computed tomography, and near-infrared fluorescence imaging enable non-invasive evaluation of CLDN18.2 expression, improving diagnosis and guiding personalized treatment. This review summarizes recent advances in CLDN18.2-targeted therapies and molecular imaging for cancer management. We outline the biomarker's biological functions and signaling pathways across cancers, highlighting the development of precision therapeutics. We also discuss applications and limitations of CLDN18.2-targeted theranostics in digestive malignancies and address clinical translation challenges and future directions.

  PublisherDOI

• In situ radiochemical doping of functionalized inorganic nanoplatforms for theranostic applications: a paradigm shift in nanooncology

  Journal of Nanobiotechnology · 2025-06-02 · 6 citations

  reviewOpen access

  In situ radiochemical doping presents a transformative approach for synthesizing radiolabeled inorganic nanoparticles (NPs) for cancer theranostics. Traditional radiolabeling techniques rely on bifunctional chelators, which often require harsh reaction conditions that can degrade the physicochemical properties of NPs. Additionally, the enzymatic dissociation of radiometals can potentially induce in vivo toxicity. In contrast, in situ doping directly incorporates radiometals into the NP crystal lattice, significantly enhancing both radiolabeling yield and radiochemical stability. This method preserves the pharmacokinetic profiles of the radiolabeled NPs, improving their theranostic efficacy. This review provides an up-to-date overview of the progress made in the development of radiolabeled inorganic nanoplatforms through in situ doping, with a focus on their stability, physicochemical characteristics, and applications in cancer theranostics. Our findings highlight the advantages in situ doping as a more efficient and stable alternative to conventional radiolabeling methods, offering substantial potential for the development of more effective cancer theranostic agents.

  PublisherOA PDFDOI

• Radiolabeled Nanogels: From Multimodality Imaging to Combination Therapy of Cancer

  Small Science · 2025-06-19 · 2 citations

  reviewOpen accessCorresponding

  Advancements in nanotechnology over the past few decades have offered tremendous possibilities toward cancer theranostics. Radiolabeled nanogels (NGs) represent a promising nanoplatform in this direction, offering a multifunctional toolset for both imaging and therapeutic interventions. This review encapsulates the progressions and potential of radiolabeled NGs in the realm of cancer research. Firstly, multifunctional radiolabeled NGs serve as potent contrast agents for multimodality imaging, enabling precise visualization of tumor sites through various techniques such as positron emission tomography, single-photon emission computed tomography, optical imaging and magnetic resonance imaging. Furthermore, by incorporating more than one therapeutic payload such as chemotherapeutic drugs, nucleic acids, and/or therapeutic radionuclides, they enable synergistic treatment modalities that address the heterogeneity of cancer cells and their microenvironment. This combination approach allows for enhanced therapeutic efficacy while minimizing systemic toxicity, addressing challenges associated with conventional cancer therapies. Furthermore, the radiolabeling of NGs provides a means for real-time monitoring of therapeutic distribution and pharmacokinetics, offering valuable insights into treatment response and optimization. Overall, radiolabeled NGs represent a promising platform for the integration of multimodality imaging and combination therapy in the fight against cancer with increased efficacy, reduced toxicity, and improved patient outcomes.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01CA169365

  NIH · $602k · 2017

• Ultrasound-Activated Piezoelectric P(VDF-TrFE) Nanoparticles for Electric Ablation of Cancer Cells

  NIH · $413k · 2019–2022

• NIH Grant R01CA16936501A1

  NIH · $302k · 2016

Frequent coauthors

• Todd E. Barnhart

  University of Wisconsin–Madison

  240 shared

• Jonathan W. Engle

  University of Wisconsin–Madison

  200 shared

• Dawei Jiang

  192 shared

• Hao Hong

  North China Electric Power University

  180 shared

• Shreya Goel

  University of Utah

  127 shared

• Stephen A. Graves

  University of Iowa

  113 shared

• Reinier Hernandez

  University of Wisconsin–Madison

  110 shared

• Hector F. Valdovinos

  Lawrence Livermore National Laboratory

  102 shared

Labs

• Weibo Cai LabPI

  Not provided