Tirazone (tirapazamine)

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.

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.

Furthermore, the spheroid size test demonstrates the superior penetration capability of N@P/T, leading to significant alterations in tumor spheroid size and morphology. Our integrated computational and experimental approach demonstrates that N@P/T effectively targets hypoxic cancer cells through specific molecular interactions, offering a promising strategy for BC treatment.

Here, a vaccine-integrated hollow MnO2 nanoplatform (TMLV), co-loaded with tirapazamine (TPZ) and lactate oxidase (LOX), is developed to orchestrate lactate-activatable multiple immune regulations against tumor...The activation of cGAS-STING pathway will further promote the cross-presentation between activated APCs and CD8+ T cells, significantly strengthening the adaptive immunity. This adjuvant-free design enabling multi-pathway immune activation might offer a novel strategy to overcome key challenges in antitumor immunotherapy.

The scaffold, composed of soybean isolate protein, polyvinyl alcohol, sodium alginate, and magnesium acetate, was loaded with doxorubicin (DOX) and tirapazamine (TPZ) to establish a sequential therapeutic cascade...Furthermore, magnesium acetate serves a dual immunomodulatory role by functioning as an immune adjuvant that facilitates CD8+ T cell activation and promotes tumor-associated macrophage repolarization towards the M1 phenotype. This multifunctional dual-drug depot demonstrates potential as an effective therapeutic platform for preventing tumor recurrence and addressing the limitations of conventional postoperative therapies.

Here, MnO2 nanosheets are synthesized with oxidase-like activity using fucoidan as a protective agent, and construct a multifunctional delivery system MnO2@DNAzyme-TPZ (MDT) by loading DNAzymes and hypoxia-activated prodrug Tirapazamine (TPZ) for tumor treatment and metastasis inhibition...MDT significantly inhibits tumor growth and metastasis in vivo in an in situ tumor model. The strategy of combining selective gene silencing based on DNAzymes with nanozymes and hypoxia-activated prodrug provides a new approach to anti-tumor metastasis therapy.

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.

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.

P2/3, N=300, Recruiting, Zhejiang Raygene Pharmaceuticals Co., Ltd | Not yet recruiting --> Recruiting

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.

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.

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.