Yang Haiyan, Zheng Guangrong, Li GuoChen, Chen Jincui, Qi Licui, Luo Yong, Ke Tengfei, Xiong Jie, Ji Xiaojuan
Department of Ultrasound, Chongqing General Hospital, Chongqing University, Chongqing, 401147, China.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
Cancer Cell Int. 2024 Dec 28;24(1):434. doi: 10.1186/s12935-024-03627-4.
Gas therapy represents a promising strategy for cancer treatment, with nitric oxide (NO) therapy showing particular potential in tumor therapy. However, ensuring sufficient production of NO remains a significant challenge. Leveraging ultrasound-responsive nanoparticles to promote the release of NO is an emerging way to solve this challenge. In this study, we successfully constructed ultrasound-responsive nanoparticles, which consisted of poly (D, L-lactide-co-glycolic acid) (PLGA) nanoparticles, natural L-arginine (LA), and superparamagnetic iron oxide nanoparticles (SPIO, FeO NPs), denote as FeO-LA-PLGA NPs. The FeO-LA-PLGA NPs exhibited effective therapeutic effects both in vitro and in vivo, particularly in NO-assisted antitumor gas therapy and photoacoustic (PA) imaging properties. Upon exposure to ultrasound irradiation, LA and FeO NPs were rapidly released from the PLGA NPs. It was demonstrated that LA could spontaneously react with hydrogen peroxide (HO) present in the tumor microenvironment to generate NO for gas therapy. Concurrently, FeO NPs could rapidly react with HO to produce a substantial quantity of reactive oxygen species (ROS), which can oxidize LA to further facilitate the release of NO. In conclusion, the proposed ultrasound-responsive NO delivery platform exhibits significant potential in effectively inhibiting the growth of breast cancer.
气体疗法是一种很有前景的癌症治疗策略，其中一氧化氮（NO）疗法在肿瘤治疗中显示出特别的潜力。然而，确保足够的NO生成仍然是一个重大挑战。利用超声响应纳米颗粒来促进NO的释放是解决这一挑战的一种新兴方法。在本研究中，我们成功构建了超声响应纳米颗粒，其由聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米颗粒、天然L-精氨酸（LA）和超顺磁性氧化铁纳米颗粒（SPIO，FeO NPs）组成，记为FeO-LA-PLGA NPs。FeO-LA-PLGA NPs在体外和体内均表现出有效的治疗效果，特别是在NO辅助的抗肿瘤气体疗法和光声（PA）成像特性方面。在超声照射下，LA和FeO NPs从PLGA NPs中快速释放。结果表明，LA可与肿瘤微环境中存在的过氧化氢（HO）自发反应生成NO用于气体疗法。同时，FeO NPs可与HO快速反应产生大量活性氧（ROS），ROS可氧化LA以进一步促进NO的释放。总之，所提出的超声响应性NO递送平台在有效抑制乳腺癌生长方面具有显著潜力。
