MnO2 coated multi-layer nanoplatform for enhanced sonodynamic therapy and MR imaging of breast cancer

Abstract

Sonodynamic therapy (SDT) is a promising new anti-tumor therapy that inhibits tumor growth by ultrasound activation of sonosensitizers to produce reactive oxygen species (ROS). However, the problems of hypoxia in the microenvironment within solid tumors and the effectiveness of SDT will decrease due to the little accumulation of sonosensitizers at the tumor site, as well as tumor cell tolerance, have limited the development of SDT. To overcome these problems, a core-shell structured nanoparticle (IR780/PLGA@MnO2 NPs) loaded with IR780 and manganese dioxide (MnO2) was developed as a nanocarrier to transport the sonosensitizer IR780 and the generated oxygen into the tumor tissue. The MnO2 shell layer of IR780/PLGA@MnO2 NPs can prevent the premature release of IR780 in the blood and also it can react with acidic and high H2O2, the generated oxygen can relieve tumor tissue hypoxia, and the generated Mn can enhance magnetic resonance imaging (MRI) signal intensity by acting as a contrast agent for MRI. More importantly, the released IR780 can produce ROS to kill tumor cells under ultrasound excitation. This PH-responsive and H2O2-triggered SDT based on the IR780/PLGA@MnO2NPs is an effective platform to inhibit tumor growth with negligible systemic toxicity. This work develops a multifunctional therapeutic integrated nanoplatform for breast cancer treatment, which is expected to be used in the clinic.

Delivery of miR‐3529‐3p using MnO2‐SiO2‐APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A

“…Nanosystems can not only be used to deliver medical cargo efficiently, but also have therapeutic functions. PTT mediated by MSA is an effective phototherapy modality that converts 1064 nm irradiation into heat to induce cell apoptosis or necrosis, and simultaneously decomposes endogenous H 2 O 2 into O 2 to reduce tumor hypoxia 46,47 . Our results indicate that cell hypoxia could be reduced by MSA treatment, and supplemental MSA addition 12 h later could enhance the hypoxia alleviation.…”

“…PTT mediated by MSA is an effective phototherapy modality that converts 1064 nm irradiation into heat to induce cell apoptosis or necrosis, and simultaneously decomposes endogenous H 2 O 2 into O 2 to reduce tumor hypoxia. 46,47 Our results indicate that cell hypoxia could be reduced by MSA treatment, and supplemental MSA addition 12 h later could enhance the hypoxia alleviation. Although miR-3529-3p was not demonstrated to contribute to hypoxia alleviation, increased miR-3529-3p expression was capable of promoting ROS production in lung carcinoma cells because of its ability to disrupt Complex III and IV activities possibly through downregulation of HIGD1A.…”

Tumor Microenvironment‐Related Sonodynamic Therapy Mediates Tumor Therapy

“…Cells transport glucose through GLUT1 and phosphorylate it into glucose 6-phosphate (G6P) under the action of hexokinase (HK). When O 2 levels are sufficient, normal cells use ATP produced by oxygen-mediated oxidative phosphorylation in mitochondria to pH-response HMCDB, EcaC, Ca@H, CR-PEG36-GBP [61,99,191,192] Relieve hypoxia CDP@HP-T, WOx NBs [37,98] H 2 O 2 cascade, relieve hypoxia IR780/PLGA@MnO 2 NPs [193] Catalytic production of H 2 O 2 , catalytic CDT Ti 3 C 2 /CuO 2 @BSA [194] Catalytic CDT PIOC@CM NPs [195] Consumption of GSH, catalytic CDT, relieve hypoxia mZMD NCS [55] GSH cascade PEG-PPMDT NPs [196] Consumption of GSH Ir-Hemin NS [197] Reverse immunosuppression HPNP [100] provide energy. When the cell is in a state of hypoxia, the cell undergoes glycolysis and uses G6P as the reaction substrate to provide power for the cell.…”

Manganese Dioxide-Based Nanomaterials for Medical Applications

“…14 For example, the physical and chemical advantages of MnO 2 nanomaterials have enabled their use in MRI, 15 FI, 16 PAI, 17 multispectral optoacoustic tomography imaging (MSOT), 18 and CT 19 for monitoring diseases. MnO 2 can also regulate the TME and is widely used in CDT, 6 PTT, 20 PDT, 21 SDT, 22 radiotherapy, 23 and immunotherapy. 24 MnO 2 nanomaterials can also reduce oxidative stress and the inflammatory response.…”