Manganese self-boosting hollow nanoenzymes with glutathione depletion for synergistic cancer chemo-chemodynamic therapy.
Xinyi CaiDeng CaiXiaozhen WangDou ZhangLong QiuZhenying DiaoYong LiuJianbo SunDa-Xiang CuiYanlei LiuTing YinPublished in: Biomaterials science (2024)
Chemodynamic therapy (CDT) has outstanding potential as a combination therapy to treat cancer. However, the effectiveness of CDT in the treatment of solid tumors is limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME). GSH overexpression diminishes oxidative stress and attenuates chemotherapeutic drug-induced apoptosis in cancer cells. To counter these effects, a synergistic CDT/chemotherapy cancer treatment, involving the use of a multifunctional bioreactor of hollow manganese dioxide (HMnO 2 ) loaded with cisplatin (CDDP), was developed. Metal nanoenzymes that can auto-degrade to produce Mn 2+ exhibit Fenton-like, GSH-peroxidase-like activity, which effectively depletes GSH in the TME to attenuate the tumor antioxidant capacity. In an acidic environment, Mn 2+ catalyzed the decomposition of intra-tumor H 2 O 2 into highly toxic ·OH as a CDT. HMnO 2 with large pores, pore volume, and surface area exhibited a high CDDP loading capacity (>0.6 g -1 ). Treatment with CDDP-loaded HMnO 2 increased the intratumor Pt-DNA content, leading to the up-regulation of γ-H2Aχ and an increase in tumor tissue damage. The decreased GSH triggered by HMnO 2 auto-degradation protected Mn 2+ -generated ·OH from scavenging to amplify oxidative stress and enhance the efficacy of CDT. The nanoenzymes with encapsulated chemotherapeutic agents deplete GSH and remodel the TME. Thus, tumor CDT/chemotherapy combination therapy is an effective therapeutic strategy.
Keyphrases
- combination therapy
- oxidative stress
- induced apoptosis
- fluorescent probe
- cancer therapy
- drug delivery
- metal organic framework
- papillary thyroid
- room temperature
- endoplasmic reticulum stress
- dna damage
- systematic review
- randomized controlled trial
- cell proliferation
- wastewater treatment
- locally advanced
- stem cells
- transcription factor
- signaling pathway
- high resolution
- single molecule
- ischemia reperfusion injury
- photodynamic therapy
- squamous cell carcinoma
- highly efficient
- radiation therapy
- cell therapy
- lymph node metastasis
- transition metal
- heat stress
- childhood cancer
- drug induced
- ionic liquid