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

Light-Activated Hypoxia-Responsive Nanoparticles for Photodynamic Chemotherapy. (PubMed, ACS Omega) - "Here, we report light-activated hypoxia-responsive nanoparticles NPs-TPZ consisting of 5,10,5,20-tetrakis-(4-aminophenyl)-porphine (TAPP) modified with four azobenzene groups, cyclodextrin (CD), and 3-aminobenzotriazine-1,4-di-N-oxide tirapazamine (TPZ) by the synergy of π-π stacking, host-guest, and hydrophobic interactions for synergistic photodynamic chemotherapy (PDT-CT)...The induced hypoxia exacerbation further accelerates the release and activation of TPZ. As a result, this hypoxia-responsive nanoparticle provides an effective strategy for the ablation of hypoxic solid tumors by synergistic PDT-CT."

Journal • Oncology • Solid Tumor

PET Imaging-Guided Dual-Function Biomimetic Nanoprobes for Sonodynamic Therapy and Chemotherapy in Triple-Negative Breast Cancer (SNMMI 2025) - "We developed CCm/RBCm@D-Ce6-TPZ, combining cancer cell membranes (CCm) for tumor targeting, red blood cell membranes (RBCm) for immune evasion, sonodynamic nanoparticles Chlorin e6 (Ce6), and hypoxic chemotherapy drug tirapazamine (TPZ) for tumor destruction... Characterization confirmed the successful synthesis of CCm/RBCm@D-Ce6-TPZ, with a particle size of approximately 198 nm. In vitro studies demonstrated the generation of ROS and strong cytotoxicity under sonodynamic therapy (SDT). PET imaging, enabled by pre-targeting strategies and click chemistry, offered precise visualization of the nanoprobe’s in vivo metabolic distribution and tumor targeting."

Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer

PET Imaging-Guided Dual-Function Biomimetic Nanoprobes for Sonodynamic Therapy and Chemotherapy in Triple-Negative Breast Cancer (SNMMI 2025) - "We developed CCm/RBCm@D-Ce6-TPZ, combining cancer cell membranes (CCm) for tumor targeting, red blood cell membranes (RBCm) for immune evasion, sonodynamic nanoparticles Chlorin e6 (Ce6), and hypoxic chemotherapy drug tirapazamine (TPZ) for tumor destruction... Characterization confirmed the successful synthesis of CCm/RBCm@D-Ce6-TPZ, with a particle size of approximately 198 nm. In vitro studies demonstrated the generation of ROS and strong cytotoxicity under sonodynamic therapy (SDT). PET imaging, enabled by pre-targeting strategies and click chemistry, offered precise visualization of the nanoprobe’s in vivo metabolic distribution and tumor targeting."

Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer

Microenvironment-activatable nanoagent for real-time NIR-II monitoring and targeted therapy of arterial restenosis. (PubMed, Biomaterials) - "This nanoplatform is constructed by co-encapsulating a novel N-oxide-based molecular probe and a hypoxia-activatable prodrug tirapazamine (TPZ) into osteopontin (OPN)-targeted liposomes...In guidewire-induced restenosis models, this system achieves simultaneous real-time monitoring of lesion progression via NIR-II imaging and significantly reduce restenosis while enhancing re-endothelialization. This study offers a promising strategy for developing high-performance theranostic nanoplatforms, enabling precise detection and improved treatment of restenosis-related diseases."

Journal • Cardiovascular • SPP1

Vascular-Targeted Nanoplatform for Enhanced Immunotherapy via Synergistic Thrombosis and Hypoxia-Activated Chemotherapy. (PubMed, ACS Appl Mater Interfaces) - "ThT@ZRR consists of thrombin and tirapazamine (TPZ) coloaded within ZIF-8 nanoparticles cloaked by RGD-modified red blood cell membranes...Notably, ThT@ZRR exhibited potent antitumor efficacy in murine melanoma (B16F10) and triple-negative breast cancer (4T1) models with distinct vascular architectures, highlighting its adaptability to heterogeneous tumor microenvironments. By integration of vascular embolization, hypoxia-activated chemotherapy, and synergistic thrombosis- and ICD-driven immune activation, this nanoplatform offers a promising strategy for enhancing cancer immunotherapy and overcoming immune resistance in solid tumors."

Journal • Breast Cancer • Cardiovascular • Hematological Disorders • Melanoma • Oncology • Solid Tumor • Thrombosis • Triple Negative Breast Cancer • CD8

Smart self-assembly of a multifunctional theranostic nanozyme for self-enhanced precise chemo/chemodynamic therapy. (PubMed, Nanoscale) - "Herein, we developed a theranostic nanozyme using Mn2+-driven self-assembly of fluorenylmethyloxycarbonyl-protected cysteine (Fmoc-Cys) as a multifunctional carrier for the first time, and co-encapsulated with tirapazamine (TPZ) and glucose oxidase (GOX)...Meanwhile, the release of Mn2+ was ideal for T1 magnetic resonance imaging (MRI), and the fluctuations of sO2 could be monitored by photoacoustic imaging (PAI). Therefore, this work presents a smart self-assembly nanozyme capable of dual-modality imaging and self-enhanced combined therapy."

Journal • Breast Cancer • Oncology • Solid Tumor

Engineering hypoxia-specific core-shell nanotherapeutics: A sequential strategy for amplified multimodal synergistic breast cancer treatment. (PubMed, J Colloid Interface Sci) - "Herein, we developed a multifunctional targeted delivery nanosystem based on the tirapazamine (TPZ)-loaded BT@M/T@T(Cu)GH cascade nanoreactor to enhance the synergistic efficacy of CDT, SDT, chemotherapy (CT) and starvation therapy (ST) against breast cancer...Additionally, the administration of BT@M/T@T(Cu)GH had negligible effects on the normal growth. Taken together, this work establishes a versatile TiO2-based nanosystem integrating tumor targeting and multi-mode synergistic therapy of breast cancer, offering a novel strategy for highly effective and precise treatment of malignancies."

Journal • Breast Cancer • Oncology • Solid Tumor • CD44

A hypoxia-activated and tumor microenvironment-remodeling nanoplatform for augmenting sonodynamic-chemodynamic-chemotherapy of breast cancer. (PubMed, Biomater Sci) - "The innovative Lip-Ce6-MnO2-TPZ nanoparticle was constructed by loading Ce6, MnO2, and hypoxia responsive drug tirapazamine (TPZ) together into a cytotoxic reactive oxygen species (ROS) responsive nanocarrier...Overall, the Lip-Ce6-MnO2-TPZ platform could induce the generation of excess ROS combined with antioxidant depletion, resulting in oxidative stress and aberrant redox homeostasis of the TME. This strategy has brought forward the idea of inducing cancer cell death by synergistically working SDT, CDT, and hypoxia-activated prodrugs to maximize the therapeutic efficacy in cancer treatment."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor

Phosphorous dendrimer-mediated biomineralization for synergistic blockade therapy and hypoxia-activated chemotherapy of tumors. (PubMed, Acta Biomater) - "Herein, we report the phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties to encapsulate a hypoxia-activated tirapazamine (TPZ) to achieve synergistic blockade therapy/chemotherapy of triple-negative breast cancer (TNBC)...The developed AK176@FN/TPZ (AFT) NCs can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and αvβ3 integrin receptors, and specifically induce mineral deposition via the inherent calcium ion adsorption property of bisphosphonate groups of dendrimers, thereby triggering tumor biomineralization for blockade therapy. The AFT-mediated biomineralization on tumor cell membranes generates tumor hypoxia, which further amplifies the chemotherapeutic effect of TPZ."

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

Multifunctional Mesoporous Silicon Nanoparticles for MRI-Based Diagnostic Imaging and Glioma Therapy. (PubMed, ACS Appl Mater Interfaces) - "This system integrates tirapazamine (TPZ), glucose oxidase (GOx), in situ-synthesized copper sulfide (CuS), and CT2A glioma cell membrane coating to enable dual tumor-targeted therapy and self-imaging capabilities...Experimental results demonstrated that HCTG-C achieves real-time MRI monitoring via GSH depletion-driven Cu valence transitions, while its self-replenishing H2O2 and oxygen-activation mechanisms significantly enhance antitumor efficacy against CT2A glioma in vitro and in vivo. By innovatively combining H2O2 self-supply cascades, hypoxia-activated chemotherapy, and ferroptosis-driven CDT, this work presents a paradigm-shifting strategy for self-imaging-guided combinatorial therapy, advancing ferroptosis-based approaches for precision glioma treatment."

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

Sulforaphane enhances cytototoxic effects of novel non-thermal plasma and Tirapazamine combined therapy in pancreatic adenocarcinoma cells (AACR 2025) - "However, the Western blots show inconsistent loss of vimentin, consistent loss of E-cadherin, and no upregulation of Cx43. While these results suggest SF has potential as an adjunct agent, further investigation is needed to understand the causes of increased cytotoxicity between SF and NTP+TPZ in pancreatic adenocarcinomas."

Brain Cancer • CNS Tumor • Glioblastoma • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDH1 • VIM

Construction of a programmed activation nanosystem based on intracellular hypoxia in cisplatin-resistant tumor cells for reversing cisplatin resistance. (PubMed, Mater Today Bio) - "The cisplatin-resistant tumor cell specific intracellular hypoxia programmed activation nanomedicine (T/C@HN NPs) was constructed by the hypoxic toxic drug tirapazamine (TPZ) and encapsulating chlorin e6 (Ce6) into HA-NI using polymer assembly technology. This project systematically evaluated the effects of T/C@HN NPs on the identification and recognition of cisplatin-resistant tumors using drug-resistant patient-derived xenograft (PDX) models. This study provides a promising avenue for the development of novel treatment of cisplatin-resistant tumors."

Journal • Oncology

Synergistic Comprehensive Activation Methods for Dual-Modality PDT and Hypoxia-Triggered Chemotherapy Guided by NIR-II Imaging beyond 1700 nm in Deep Tumors. (PubMed, Small) - "Moreover, PDT aggravates tumor hypoxia, which in turn activates the hypoxia-activatable prodrugs like tirapazamine, resulting in a synergistic antitumor effect. With NIR-IIc imaging-guided dual-modality PDT, this study introduces a groundbreaking approach that unites Type I/II PDT with chemotherapy, significantly advancing the precise and effective treatment of deep hypoxic tumors."

Journal • Oncology

A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) With cTACE for Intermediate-stage Liver Cancer. (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Porphyrin-based covalent organic framework with NIR absorption: Preparation, hyaluronic acid modification, and cascading a hypoxia-sensitive drug for synergistic therapy of cancer phototherapy/chemotherapy. (PubMed, Int J Biol Macromol) - "Second, the hypoxia-responsive drug tirapazamine (TPZ) and tumor-targeted hyaluronic acid (HA) were loaded to Por-COF through the electrostatic effect to prepare a multifunction nanomedicine (Por-COF@TPZ/HA) that could simultaneously produce abundant reactive oxygen species and high temperature via808 nm laser irradiation...Combined photodynamic-photothermal therapy and chemotherapy had an outstanding synergistic effect. This work provides a promising method for Por-COF preparation and a feasible strategy for the synergistic therapy of cancers."

Journal • Oncology

5-Aminolaevulinic Acid-Mediated Photodynamic Therapy Combined with Tirapazamine Enhances Efficacy in Ovarian Cancer. (PubMed, Biomedicines) - "The enhanced therapeutic effect may be attributable to the inhibition of the hypoxia-inducible factor-1α/vascular endothelial growth factor axis and PI3K/Akt/mTOR pathway. 5-ALA-PDT combined with TPZ can overcome both the hypoxic state of ovarian cancer tissues and the increased hypoxia induced by PDT, thereby inhibiting tumour growth."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • HIF1A

Effect of conventional physiotherapy versus strain counter for trapezitis patients. (PubMed, Bioinformation) - "We found that, group 2 showed significant improvements in range of motion, pain and neck disability outcome scores. Thus, that SCS can be used as a low-cost and effective treatment for trapezitis."

Journal • Musculoskeletal Pain • Pain

Nanocapsules with dual-targeting of cell and mitochondria functions for enhanced hypoxia-activated drug therapy. (PubMed, Chem Commun (Camb)) - "The cell and mitochondria dual-targeting nanocapsules reported here could exacerbate tumor hypoxia to activate a hypoxia-activated drug, tirapazamine, producing benzotriazinyl radicals and ˙OH, which are capable of killing tumor cells via DNA damage. In addition, mitochondrial dysfunction can result from the accumulation of ˙OH. This chain reaction triggers a surge in ROS that can effectively increase the therapeutic efficiency of the nanocapsules."

Journal • Metabolic Disorders • Oncology

Coenzyme Q10 as an Inhibitor of Effector Release from One-Electron-Reduced Bioreductive Anticancer Prodrugs. (PubMed, Molecules) - "Evidence is put forward suggesting that radical anions can undergo an electron transfer to ubiquinone (CoQ10, UQ) in competition with the fragmentation of the radical anions releasing effectors. The prior inhibition of the synthesis of UQ in cells is put forward as a possible approach to increase the effectiveness of such prodrugs in killing hypoxic tumor cells."

Journal • Oncology

A Phase II/III Trial Comparing Transarterial Tirapazamine Embolization (TATE) with CTACE for Intermediate-stage Liver Cancer. (clinicaltrials.gov) - P2/3 | N=300 | Not yet recruiting | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P2/3 trial • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Evaluate the Effect of Tirazamine on Primary Liver Cancer. (clinicaltrials.gov) - P1/2 | N=16 | Terminated | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P1/2 trial • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Tumor Microenvironment-Responsive Nanodrug for Embolotherapy and Enhanced Chemotherapy. (PubMed, ACS Appl Mater Interfaces) - "This study presents a mesoporous polydopamine-based (MPDA) drug delivery platform modified by engineered fusion proteins, which can specifically embolize tumor blood vessels and deliver the hypoxia-activated prodrug tirapazamine (TPZ)...This nanodrug can actively target HER-2, interact with MMP-2 in the tumor microenvironment (TME), and embolize blood vessels; then, under TME acidic circumstances, MPDA releases TPZ, which is activated by hypoxia aggravated by embolization, and kills tumors. This embolization strategy, which is activated only under specific conditions, is extremely safe, and it compensates for the inadequacies of conventional embolization therapy, while also addressing the issue of hypoxia deficiency in hypoxia-activated prodrug therapy."

Biomarker • Journal • Oncology • MMP2

TATE and KN046 in MCRC (clinicaltrials.gov) - P2 | N=42 | Terminated | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P2 trial • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

Hypoxia-driven mobilization of altruistic cancer stem cells in platinum-treated head and neck cancer. (PubMed, Front Immunol) - "These cells displayed increased proliferation and invasion upon cisplatin treatment, suggesting a role in niche defense...Notably, inhibiting hypoxia alone with tirapazamine did not reduce TSD+ CSCs, CTCs, or R-CSCs...Additionally, the pre-clinical study provides a novel non-genetic mechanism of therapy resistance-the altruistic tumor self-defense. The tumor microenvironment, through the emergence of TSD+ CSCs, appears to act collectively to defend the tumor self-identity by hijacking an altruistic stem cell niche defense mechanism."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EPAS1

Optimizing interventional therapy: A homogeneous lipiodol formulation of Tirapazamine and Sorafenib responsive to post-embolization microenvironment. (PubMed, J Control Release) - "In summary, this study developed a novel embolization drug formulation based on embolic hypoxic microenvironment. The synergistic mechanism of TPZ and SFB enhances the therapeutic effects of hypoxia-activated prodrugs and mitigates the adverse effects of hypoxia."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor