Tirazone (tirapazamine) / Teclison, SRI International - LARVOL DELTA

Oxygen-Adaptive Covalent Organic Framework Nanoarchitectonics with High Photothermal Conversion Efficiency for Quadruple-Modal Tumor Therapy. (PubMed, Adv Healthc Mater) - "Remarkably, GTPZ exhibits a record-high photothermal conversion efficiency of 72% among COF-based nanomedicines, enabling spatiotemporal control over hypoxia-activated tirapazamine (TPZ) release to generate cytotoxic radicals...In MCF-7 models, GTPZ achieves high tumor suppression through synergistic lipid peroxidation, cell cycle arrest, and ferroptosis. This work provides a paradigm for designing intelligent nanomedicines capable of dynamically adapting to TME."

Journal • Oncology

Cholesterol Metabolism Regulated Nanoliposome Ameliorates Chemo/Photothermal Therapy Reversing CD8+ T Cell Exhaustion. (PubMed, Exploration (Beijing)) - "Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses...When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Rationally designed thiazole-based COF with multiphoton activity for drug delivery and synergistic therapy of deep-seated tumors. (PubMed, J Nanobiotechnology) - "Furthermore, tirapazamine (TPZ), a hypoxia-activated chemotherapeutic drug, was encapsulated into DT-COF pores with anastomosing dimensions (drug loading efficiency = 76.2%)...Additionally, DT-COF consumed the limited intratumoral oxygen to generate singlet oxygen, which further cooperated with the hypoxic tumor microenvironment to promote the activation of TPZ, thereby achieving synergistic antitumor therapy through the combination of photodynamic therapy and chemotherapy. This study provides a new strategy for the development of MPAPSs and demonstrates their potential in cancer theranostics."

Journal • Oncology • PAPSS1

A phase 2, open-label single-arm, multi-center study of trans-arterial tirapazamine embolization (TATE) combined with nivolumab (nivo) in patients with advanced immunotherapy-refractory hepatocellular carcinoma (HCC). (ASCO-GI 2026) - P2 | "TATE plus nivo is promising in the salvage setting of advanced HCC patients who failed at least one line of immunotherapy. Further investigation is warranted to confirm the efficacy of this combination. Best overall response in all evaluable patients."

Clinical • IO biomarker • Metastases • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

PISTOL MRI allows noninvasive assessment of changes in tumor oxygenation post hypoxia targeted therapy. (PubMed, Sci Rep) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Hydroxylated dendrimer nanogels co-deliver drugs and cytokines for chemoimmunotherapy of glioma. (PubMed, Mater Today Bio) - "Herein, we develop a dual pH/reactive oxygen species-responsive dendrimer nanogel (DNG) platform based on generation 3 poly(amidoamine) (G3 PAMAM) dendrimers for co-delivery of the hypoxia-activated prodrug tirapazamine (TPZ) and the immunomodulatory cytokine interferon-gamma (IFN-γ)...Leveraging the rich hydroxyl groups and the enhanced permeability and retention effect of DNGs, the DNGs-TPZ/IFN-γ can penetrate the BBB and demonstrate potent therapeutic efficacy in an orthotopic mouse glioma model. The developed DNGs-TPZ/IFN-γ with a simple composition may be developed to co-deliver drugs and cytokines to tackle other cancer types."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • IFNG

NIR-light triggered photodynamic therapy combined with hypoxia activated chemotherapy for anti-tumor effects. (PubMed, Nanoscale) - "To overcome these limitations, we rationally designed a composite upconversion nanoparticle, UCNPs@MSN-Ce6/TPZ (UMCT), integrating the photosensitizer chlorin e6 (Ce6) and the hypoxia-activated prodrug tirapazamine (TPZ) for synergistic PDT and chemotherapy...Significantly, UMCT shows effective accumulation at the tumor site, achieving a potent and synergistic tumor-suppressing effect both in vitro and in vivo. This work provides a promising strategy for designing more efficient PDT nanoplatforms and advancing their biomedical applications."

Journal • Oncology

Facile Preparation of Nanoscale Chlorin-Integrated Covalent Organic Frameworks for Combined Chemophototherapy. (PubMed, Biomacromolecules) - "The optimized TPCCOF morphology was used to load tirapazamine (TPZ), forming the biocompatible TPCCOF@TPZ nanoplatform...This synergistic PDT/PTT/chemotherapy combination effectively suppresses 4T1 tumor cell proliferation under both normoxic and hypoxic conditions. Our work advances nanoscale COF design for multimodal cancer therapy and supports preclinical development of porphyrin-based photosensitizers."

Journal • Oncology

Microbiota-directed lactic acid depleting nanoenzyme reactivates antitumor immunity and chemosensitivity in hypoxic tumor. (PubMed, Mater Today Bio) - "To tackle this challenge, we engineered a delivery platform (TML NPs) for lactate oxidase (LOX) and chemotherapeutic drug tirapazamine (TPZ) by modifying the carrier with metronidazole (MTZ), an antibiotic bearing hypoxia-responsive functional group. By directly targeting the symbiotic anaerobic bacterial metabolism, this strategy introduces a novel paradigm for modulating TME acidification, reversing the LA-mediated suppression of anti-tumor immune responses and chemosensitivity. Our strategy offers a promising translational platform for the precise treatment of TNBC and other hypoxic malignancies."

Journal • Oncology • Triple Negative Breast Cancer

AMFR-mediated ER-phagy regulation and therapeutic targeting in osteosarcoma: a multifunctional nanoplatform strategy. (PubMed, J Nanobiotechnology) - "The nanoplatform, thoroughly characterized via established methods, co-delivers CRISPR-Cas9 RNP and tirapazamine to disrupt AMFR and enhance reactive oxygen species production, inhibiting tumor growth in mouse models...Second near-infrared window imaging validates targeted drug delivery. This approach provides a precise strategy to disrupt hypoxia tolerance in OS and potentially other hypoxia-tolerant tumors, offering promise for improved therapeutic outcomes."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Targeted Protein Degradation

Dual-Responsive Nanodelivery System Synergizes Elevation in Hypoxia with PD-L1 Blocking to Activate Systemic Immunity and Inhibit Distant Tumors. (PubMed, ACS Appl Mater Interfaces) - "This study has constructed a nanomicelle (HACA/GOx@AF/TPZ) that is composed of a coassembly of hyaluronic acid-cinnamaldehyde Schiff base (HACA), glucose oxidase (GOx), tirapazamine (TPZ), and acriflavine (AF)...Meanwhile, AF can specifically inhibit HIF-1α through a multistage response, downregulating the expression of VEGF and facilitating the conversion of the tumor microenvironment (TME) to an antitumor TME, inducing dendritic cell maturation and polarization of M2 macrophages to M1. The "hypoxia-activated immune modulation" combination therapy strategy using HACA/GOx@AF/TPZ may provide more possibilities for combined tumor treatment."

IO biomarker • Journal • Immune Modulation • Immunology • Oncology • HIF1A

Photo-Empowered Macrophage-Based Drug Delivery System Overcomes Motility Suppression and Significantly Enhances Deep Tumor Drug Delivery. (PubMed, Adv Sci (Weinh)) - "In this work, the PEM system is loaded with two antitumor drugs: doxorubicin (Dox) and tirapazamine (TPZ). Particularly after deep infiltration into tumor tissues, the PEM system efficiently eradicates hypoxic and drug-resistant tumor cells, showcasing remarkable performance. This innovative PEM strategy provides a new approach for deep tumor drug delivery and addressing multidrug resistance, holding great promise for a significant breakthrough in antitumor therapy."

Journal • Oncology

Supramolecular Aggregation-Induced Emission Photosensitizer Encapsulated by Cucurbit[8]uril Nanocavity Boosts Hypoxia-Activated Tumor Therapy. (PubMed, ACS Appl Nano Mater) - "When coadministered with the hypoxia-activated chemotherapeutic tirapazamine (TPZ), we found that 2SC-3/CB[8] further amplified TPZ's antitumor efficacy in MDA-MB-231 breast cancer cells...In addition, we found that CB[8]-induced depletion of intracellular spermine further contributed to the death of the tumor cells. Together, these findings highlight the potential of combining supramolecular photosensitizers with hypoxia-activated chemotherapy as a promising and synergistic strategy for the treatment of solid tumors."

Journal • Breast Cancer • Oncology • Solid Tumor

Tumor necrosis-induced expansion of anti-tumor T cells enhanced the efficacy of immune checkpoint inhibitors (ICIs) and salvaged patients with immunotherapy-refractory cancers (SITC 2025) - P2 | "Patients received ICI Q3W IV starting day 1, Trans-arterial Tirapazamine embolization (TATE) on Days 8, 29 and on demand to achieve optimal tumor necrosis confirmed by MRI scans...Further investigation is warranted to confirm the efficacy of expanded T cells.Acknowledgements Funding was provided by Teclison, Inc.Trial Registration NCT03259867, NCT04701476Ethics Approval UCI #16-94; China Medical Univ. LT004/CMUH113-REC1-025; Chang-Gung Memorial Linkou Hospital, LT004/#202400098A0; TSGH LT004/B202501001Abstract 594 Figure 1Request permissionsExpansion and newly generated CDR3 clones after tumor necrosis-inducing therapy"

Checkpoint inhibition • Clinical • IO biomarker • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Phase 2 single-arm study of Trans-Arterial Tirapazamine Embolization (TATE) plus pembrolizumab for liver metastatic colorectal cancer who have progressed on at least two lines of chemotherapy (SITC 2025) - P2 | "The most common adverse events were nausea, transient elevation of AST and ALT, consistent with safety profile of TATE.Conclusions Combination of TATE with pembro shows promising efficacy for treatment refractory mCRC with an acceptable safety profile. A follow-up randomized control trial is underway to assess efficacy compared to standard of care chemotherapy.Acknowledgements Funding was supported by Teclison, Inc.Trial Registration NCT03259867, NCT04701476Ethics Approval Ethics approval was obstained by the IRB of each participating hospitals, including UC-Irvine Medical Center, CA, USA (UCI IRB HS#2017-3393, UCI 16-94); Chinese Medical College, Taiwan; Triservice General Hospital, Taiwan.Abstract 492 Figure 1Request permissionsAbscopal effect in lung lesions after metastatic liver lesions were treated with TATE"

Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Nitroreductase (NTR)-Triggered Degradable Polymeric Sulfur Dioxide (SO2) Prodrug. (PubMed, Biomacromolecules) - "Hypoxia-activated anticancer drug tirapazamine (TPZ) is encapsulated into the polymeric nanoaggregates, and 63% drug release is observed at pH 6.0 in the presence of NTR. Anticancer activity of the polyprodrug (SO2 as a cytotoxic agent) and TPZ-loaded polymeric nanoaggregate (SO2 and TPZ as cytotoxic agents) is demonstrated with cobalt chloride (CoCl2, hypoxia mimetic mediator). Overall, the present work reveals the impact of the NTR-responsive degradable polyprodrug as an anticancer therapeutic and gives a new perspective on enzyme-responsive gas therapy."

Journal • Oncology

Membrane calcification-reinforced tumor therapy mediated by versatile hollow manganese dioxide nanoplatform. (PubMed, Colloids Surf B Biointerfaces) - "Herein, based on the distinctive biological impact of cell membrane calcification, we constructed a multi-functional nanoplatform of hollow manganese dioxide (MnO2) encapsulated with calcium carbonate (CaCO3) and a hypoxia-activated anticancer prodrug tirapazamine (TPZ)...Meanwhile, aggravated hypoxia within tumor cells caused by membrane calcification also activates TPZ cytotoxicity, which can produce highly active and cytotoxic benzotriazinyl (BTZ) radical, leading to cell death and anti-tumor effect. The synergy of multiple effects enables the carefully designed platform of HMn@CaT to demonstrate excellent tumor inhibition both in vitro and in vivo, hence establishing a novel approach for tumor treatment."

Journal • Oncology

MOF-Based Nanoplatform Enables Synergistic Hypoxia-Activated Chemotherapy and Chemodynamic Therapy for Colon Cancer. (PubMed, ACS Appl Mater Interfaces) - "This platform codelivered β-lapachone (Lap) and the hypoxia-activated prodrug tirapazamine (TPZ) within a pH-responsive, biodegradable, copper-doped, zeolitic imidazolate framework...The H2O2 generated from this process served as a substrate for Cu+-mediated Fenton-like reactions, leading to the production of highly cytotoxic hydroxyl radicals and thereby enhancing the effect of chemodynamic therapy (CDT). The experimental findings confirmed that this strategy effectively integrates hypoxia-activated chemotherapy with CDT, resulting in significantly improved therapeutic outcomes compared to monotherapies."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • NQO1

Localized Oxygen Delivery via High-Pressure-Synthesized Oxygen Gas-Entrapping Materials Enhances Radiotherapy Efficacy and Improves Outcomes in Solid Tumors (ASTRO 2025) - "Mice in a third cohort were administered tirapazamine (0.12 mmol/kg/day) 30 minutes prior to irradiation... These findings highlight O2-GeMs as a promising strategy to overcome tumor hypoxia, enhance radiotherapy efficacy, and improve survival outcomes in solid tumors."

Clinical • Oncology • Sarcoma • Solid Tumor

Dual-Functional Biomimetic Nanoprobes for PET Imaging-Guided Sonodynamic Therapy and Chemotherapy of Triple-Negative Breast Cancer. (PubMed, ACS Appl Mater Interfaces) - "The nanoprobe encapsulates chlorin e6 (Ce6) for sonodynamic therapy (SDT) and tirapazamine (TPZ), a hypoxia-activated prodrug, to enable synergistic hypoxia-responsive chemotherapy...Notably, treatment mitigated splenomegaly and normalized aberrant immune cell counts, underscoring the critical role of immunomodulation in TNBC management. Hybrid biomimetic nanoprobes can overcome key limitations of TNBC therapy, offering a promising platform for future clinical translation."

Journal • Breast Cancer • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer

ZnO-Based Nanoparticles for Targeted Cancer Chemotherapy and the Role of Tumor Microenvironment: A Systematic Review. (PubMed, Int J Mol Sci) - "Chemotherapeutic agents (doxorubicin, 5-fluorouracil, docetaxel, cisplatin, gemcitabine, and tirapazamine) were loaded into ZnO-based carriers, with improved anticancer efficacy compared to free drug formulations, particularly in multidrug-resistant cell lines and in vivo murine xenografts. ZnO-NPs might constitute a versatile and promising strategy for targeted cancer chemotherapy, offering synergistic anticancer effects and improved safety profiles. Future studies emphasizing long-term toxicity, immune responses, and scalable production could lead to clinical translation of ZnO-based nanomedicine in oncology."

Biomarker • Journal • Review • Metabolic Disorders • Oncology

Hypoxia-amplifying polymer nanoprodrugs for sonodynamic chemotherapy for breast cancer and bone metastasis via in situ thrombogenesis. (PubMed, Mater Horiz) - "The nanoprodrug (DPTT) was fabricated via co-loading a sonodynamic semiconducting polymer (SP) and a hypoxia-activated prodrug, tirapazamine (TPZ), into an ROS-responsive nanomicelle decorated with thrombin on the nanoparticle surface...Remarkably, this therapeutic approach is demonstrated to achieve near-complete eradication of subcutaneous 4T1 breast tumors and substantial inhibition of bone metastasis progression in murine models. Our work presents a novel vascular disruption strategy for hypoxia potentiation, offering a promising therapeutic paradigm for treating hypoxic solid and metastatic tumors."

Journal • Breast Cancer • Oncology • Solid Tumor

Sono-triggered nanoamplifier mediates ferroptosis-immune regulation against bacterial pneumonia. (PubMed, J Control Release) - "In this study, we surprisingly discovered that tirapazamine (TPZ), a clinical hypoxia-activated anticancer prodrug, exhibits potent bacterial ferroptosis-inducing capability via multimodal metabolic interference, suggesting its repurposing potential for pneumonia treatment...Notably, the resulting ferroptotic bacteria function as endogenous immunostimulants, subsequently trigger a cascade of immunological responses to establish an antimicrobial-favorable microenvironment. Such RMRT nanoamplifier presents a safe, efficient, and easily accessible strategy that synergizes ferroptosis-associated metabolic regulation and immune activation to combat MDR bacterial pneumonia."

Journal • Infectious Disease • Oncology • Pneumonia • Respiratory Diseases

Tumor Microenvironment Responsive TPZ-Loaded Core-Shell Polymeric Nanoparticles for Selective Cancer Bioreductive Therapy. (PubMed, Adv Pharm Bull) - "To tackle this, we designed hypoxia-responsive Au-PEI-Azo-mPEG nanoparticles (NPs) denoted as APAP NPs for targeted delivery of hypoxia-activated prodrug (HAP), tirapazamine (TPZ) to hypoxic breast cancer cells...APAP NPs elicited comparable cytotoxicity upon MDA-MB-231 cancer cells lowering TPZ IC50 to 7.46 µg/mL after 24 h. And were capable of enhanced ROS generation (P<0.001), and reduced mitochondrial membrane potential under hypoxia condition compared to the control (P<0.0001). Further, these NPs induced widespread apoptosis in both 2D and 3D cancer cell culture (P<0.0001), significantly reduced cell adhesion density (P<0.01), increased cell uptake by ~100 folds under hypoxia condition, and destroyed large MCF-7 spheroids by 72 h. Together, APAP@TPZ as biocompatible, and multi-stage activating platforms afford deepened penetration of HAP to hypoxic tumor core, where PEG detachment and TPZ bioreduction into its active form promote selective and..."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor

A photoactivatable nano-liposome containing tripartite therapeutics for photothermal-triggered chemotherapy. (PubMed, J Mater Chem B) - "In view of the unique characteristics of nanosystems that can deliver drugs in an effective and safe manner, we report photoactivatable nano-liposomes containing a hypoxia-responsive prodrug tirapazamine (TPZ), glucose oxidase (GOx) and indocyanine green (ICG) for photothermal-triggered chemotherapy of subcutaneous metastatic breast cancer...Therefore, photothermal-triggered chemotherapy is achieved by IGT@NPs, which leads to the effective inhibition of primary tumor growth and metastatic tumor occurrence in subcutaneous 4T1 tumors. This current study thus provides a photoactivatable nanosystem containing tripartite therapeutics for cancer treatment with controllable and combined functions."

Journal • Breast Cancer • Oncology • Solid Tumor