Pulmonary Delivery of Theranostic Nanoclusters for Lung Cancer Ferroptosis with Enhanced Chemodynamic/Radiation Synergistic Therapy.
Yingbo LiJie YangGuangying GuXu GuoChunbo HeJiemei SunHongyan ZouHongbin WangShuang LiuXiaona LiShujun ZhangKai WangLili YangYing JiangLina WuXilin SunPublished in: Nano letters (2022)
Inefficient tumor accumulation and penetration remain as the main challenges to therapy efficacy of lung cancer. Local delivery of smart nanoclusters can increase drug penetration and provide superior antitumor effects than systemic routes. Here, we report self-assembled pH-sensitive superparamagnetic iron oxide nanoclusters (SPIONCs) that enhance in situ ferroptosis and apoptosis with radiotherapy and chemodynamic therapy. After pulmonary delivery in orthotopic lung cancer, SPIONCs disintegrate into smaller nanoparticles and release more iron ions in an acidic microenvironment. Under single-dose X-ray irradiation, endogenous superoxide dismutase converts superoxide radicals produced by mitochondria to hydrogen peroxide, which in turn generates hydroxyl radicals by the Fenton reaction from iron ions accumulated inside the tumor. Finally, irradiation and iron ions enhance tumor lipid peroxidation and induce cell apoptosis and ferroptosis. Thus, rationally designed pulmonary delivered nanoclusters provide a promising strategy for noninvasive imaging of lung cancer and synergistic therapy.
Keyphrases
- hydrogen peroxide
- cell death
- sensitive detection
- pulmonary hypertension
- iron oxide
- fluorescent probe
- high resolution
- nitric oxide
- stem cells
- emergency department
- computed tomography
- radiation therapy
- oxidative stress
- cell proliferation
- magnetic resonance imaging
- squamous cell carcinoma
- energy transfer
- fluorescence imaging
- endoplasmic reticulum stress
- drug delivery
- single molecule
- water soluble
- rectal cancer
- replacement therapy
- smoking cessation
- walled carbon nanotubes