<p>Combinational phototherapy and hypoxia-activated chemotherapy favoring antitumor immune responses</p>

Abstract

Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment. Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis. Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs). Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes. Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.

Targeting ferroptosis in osteosarcoma

“…Tirapazamine (TPZ) has been identified for targeting hypoxic tumour cells and previously as an adjuvant for cisplatin to enhance its efficacy [66] . Recently, TPZ is often dependent on nanoplatform and combined with phototherapy for its hypoxia-activated prodrug effect, and a variety of TPZ-dependent photodynamic therapies have been validated for significant efficacy which is closely correlated with the production of ROS [67] , [68] , [69] . However the specific association of TPZ with ROS and the cell killing mechanisms involved remain elusive.…”

Firing up the Tumor Microenvironment with Nanoparticle-Based Therapies

“…Jiang et al targeted tumor hypoxia with nanoparticle-engineered CXCR4-overexpressing adipose-derived stem cells [ 62 ]. Hypoxia-activated chemicals such as tirapazamine (TPZ) when modified with PEG-PCL have been proven to trigger ICD and boost dendritic cell (DC) maturation, subsequently activating toxic T lymphocytes [ 63 ]. Nanoscale metal-organic frameworks have emerged as unique carriers for immunoadjuvants by generation of reactive oxygen species (ROS) for ICD and in situ cancer vaccination [ 64 ].…”

Bone-Targeted Erythrocyte-Cancer Hybrid Membrane-Camouflaged Nanoparticles For Enhancing Photothermal And Hypoxia-Activated Chemotherapy of Bone Invasion By OSCC

“…Synthesis of polyester H40-poly(ethylene glycol) (H40-PEG) and H40-PEG NPs were performed as previously described [43]. H40-PEG loading TPZ/IR780 nanoparticles were prepared using the oil-in-water emulsion solvent diffusion method as follows: H40-PEG (25 mg) and IR780 (2.5 mg) were dissolved in 5 mL of chloroform while TPZ was dissolved in 5 mL of deionized water [44]. Both solutions were mixed and ultrasonicated.…”