Metal–Organic Framework (MOF)‐Based Ultrasound‐Responsive Dual‐Sonosensitizer Nanoplatform for Hypoxic Cancer Therapy

Abstract

Sonodynamic therapy (SDT), which uses reactive oxygen species to target tumors, has shown promise in the management of unresectable cancers. However, the hypoxic tumor environment limits SDT efficiency, making complete tumor destruction challenging. Here, a dual-sonosensitizer nanoplatform is developed by loading an alkyl radical generator (2,2-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) onto a zirconium metal-organic framework (Zr-MOF). The Zr-MOF@AIPH nanoparticles (NPs) can produce singlet oxygen, which can kill tumor cells under normoxic conditions, as well as alkyl radicals, which can kill tumor cells under both normoxic and hypoxic conditions. The combination of these free radicals further enhances SDT efficiency. Meanwhile, the nitrogen generated owing to AIPH decomposition can reduce the cavitation threshold and enhance the acoustic cavitation effect, thereby promoting NP penetration at the tumor site. Moreover, Zr-MOF@AIPH NPs exhibit good photoacoustic, fluorescence, and ultrasound imaging abilities due to their porphyrin-based structure and the nitrogen generated, which can remotely control NP delivery and determine the optimal therapeutic time window, ensuring the maximization of SDT efficiency. In vitro and in vivo examinations prove the superior antitumor efficacy, excellent biocompatibility, and favorable imaging ability of Zr-

Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication ofPseudomonas aeruginosaBiofilms

“…The prolongation of the duty cycle was associated with decreased CV staining and decreased bacterial viability in the XTT assay (Figure S2a,d), with similar changes being observed for the increases in power (Figure S2b,e) and frequency (Figure S2c,f), consistent with enhanced biofilm clearance. To further confirm the NP-induced disruption of the biofilm barrier and the associated bacterial killing, the biofilms were cultured in confocal dishes and subjected to PBS, US, MEM, MN+US, MPN+US, or TPMN+US treatment, with US performed using optimal therapeutic settings (1.5 W/cm 2 , 50% duty cycle, 1 MHz). − After treatment, these biofilms were stained with CV (Figure a) and analyzed by the XTT assay (Figure b). Relative to the control group and other experimental groups, TMPN treatment was associated with highly efficient dissociation of the integrity of the biofilm and bacterial killing.…”

Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma

“…Of the many signaling mechanisms of NO, it is appreciated that epigenetic regulation has gained ground in recent years. NO promotes an immunosuppressive microenvironment by modifying the redox state of cells, reprogramming cellular metabolism, and inducing changes in nucleic acids, lipids, and proteins [ 29 , 59 , 60 , 61 , 62 , 63 ]. All these effects of NO in melanoma are also supported by our results.…”

Curcumin- and resveratrol-co-loaded nanoparticles in synergistic treatment of hepatocellular carcinoma

“…Tumour volume was calculated using the following formula: tumour volume (mm 3 ) = 0.5 × length × width 2 . The mice were sacrificed on Day 21 posttreatment, and the frozen tumour tissue sections were incubated with a terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) reaction mixture (Roche Diagnostics) at 37 °C for 1 h. The slides were then visualized under a fluorescence microscope [ 57 ]. Additionally, routine Ki-67 immunohistochemistry was carried out according to the manufacturer’s instructions and visualized under a fluorescence microscope [ 57 ].…”