Nano-enabled coordination platform of bismuth nitrate and cisplatin prodrug potentiates cancer chemoradiotherapy via DNA damage enhancement.
Yin-Chu MaXin-Feng TangYou-Cui XuWei JiangYong-Jie XinWei ZhaoXu HeLi-Gong LuMei-Xiao ZhanPublished in: Biomaterials science (2021)
The combination of chemotherapy and radiotherapy (chemoradiotherapy) is a promising strategy, extensively studied and applied clinically. Meanwhile, radiosensitizers play an important role in improving clinical radiotherapy therapeutic efficacy. There are still some disadvantages in practical applications, because radiosensitizers and drugs are difficult to deliver spatio-temporally to tumor sites and work simultaneously with low efficiency for DNA damage and repair inhibition, leading to an inferior synergistic effect. Herein, a suitable radiosensitizer of nano-enabled coordination platform (NP@PVP) with bismuth nitrate and cisplatin prodrug is developed by a simple synthetic route to improve the effectiveness of chemo-radiation synergistic therapy. When NP@PVP is internalized by a tumor cell, the bismuth in NP@PVP can sensitize radiation therapy (RT) by increasing the amount of reactive oxygen species generation to enhance DNA damage after X-ray radiation; meanwhile, the cisplatin in NP@PVP can inhibit DNA damage repair with spatio-temporal synchronization. NP@PVP is demonstrated to exhibit higher sensitization enhancement ratio (SER) of 2.29 and excellent tumor ablation capability upon irradiation in vivo in comparison with cisplatin (SER of 1.78). Our strategy demonstrates that the RT sensitization effect of bismuth and cisplatin based NP@PVP has great anticancer potential in chemo-radiation synergistic therapy, which is promising for clinical application.
Keyphrases
- dna damage
- locally advanced
- radiation therapy
- rectal cancer
- cancer therapy
- radiation induced
- dna repair
- oxidative stress
- squamous cell carcinoma
- reactive oxygen species
- nitric oxide
- early stage
- photodynamic therapy
- randomized controlled trial
- drug delivery
- systematic review
- high throughput
- visible light
- oxide nanoparticles
- single cell
- magnetic resonance imaging
- risk assessment
- atrial fibrillation
- magnetic resonance