Research progress on nanoformulations for protecting radiation-induced intestinal injury
[Background]Radiation-induced acute and chronic intestinal injury is a common complication in patients with abdominal/pelvic tumors such as prostate cancer and colorectal cancer.The pathogenesis of acute radiation-induced intestinal injury is mainly related to damage to intestinal epithelial cells,vascular endothelial cells,and microbial and immune barriers.Conversely,the chronic radiation-induced intestinal injury is associated with fibrosis of intestinal wall tissue.At present,as an cytoprotective agent in cancer radiotherapy,amifostine has been approved for protecting against radiation-induced intestinal injury.However,its clinical application is limited by some drawbacks such as short half-life and significant side effects.Therefore,there is an urgent need to develop new drug formulations for radiation-induced intestinal injury protection.[Progress]Currently,drug protection remains a key focus in preventing radiation-induced intestinal injury.It is well known that,the reactive oxygen species(ROS)induced by radiation is the key factor in radiation-induced intestinal injury.Consequently,clearing ROS generated by radiation may be a potential strategy for preventing radiation-induced intestinal injury.Except for amifostine,some other synthetic small molecule compounds such as misoprostol,sucralfate,aminosalicylic acid,and glutamine have been tested to prevent radiation-induced intestinal injury.However,the effects in human body are undetermined due to the lack of clinical reseach evidence.In addition,the strategy of"new use for old drugs"provides new ideas for the development of radiation-induced intestinal injury protective drugs.Metformin,cimetidine,BCN057,sitagliptin and nicotinamide mononucleotide have been founded to effectively prevent radiation-induced intestinal injury.Compared with synthetic chemical drugs,natural plant compounds such as polyphenols and flavonoids,including apigenin extracted from celery,epigallocatechin-3-gallate(EGCG),resveratrol,γ-aminobutyric acid,sanguine and curcumin,have also been proven to have good radiation protection effects due to their antioxidant ability.In addition,some Chinese herbal extracts with anti-inflammatory and antioxidant effects,such as ginsenoside Rd and ginsenoside Re,rosin,baicalin,thymoquinone and Goji Berry polysaccharides,have shown their potential in preventing or mitigating radiation-induced intestinal injury.However,there are still some challeges with the above strategies.For example,small molecule compounds have shown some limitaitons,such as short half-life time,poor stability,and low bioavailability.With the rapid development of carrier materials and formulation technology,nanomedicine has become an alternative strategy due to its advantages in prolonging drug half-life,reducing toxicity,and improving drug bioavailability.Currently,nanoparticles,such as cerium oxide nanoparticles and carbon based nanoparticles,have been reported to prevent radiation-induced intestinal injury due to their inherent radiation protection properties.Moreover,nanomedicine prepared by encapsulating some small moleculer drug into nanocarriers or by self-assembly methods have been reported to overcome the limitations of free drug,thus improving efficacy of radiation protection.Therefore,nanomedicines are expected to become a widely applicable strategy for preventing radiation-induced intestinal injury.[Perspective]We first summarizes the pathogenesis of acute and chronic radiation-induced intestinal injury,and then reviews the current research status and clinical application progress in strategies in the prevention of radiation-induced intestinal injury.It also addresses the key challenges in the design of protective formulations against radiation-induced intestinal injury,highlighting the ideal design of nanomedicines for radiation-induced injury prevention.In the future,important strategies for protecting against radiation-induced intestinal injury will include clearing ROS generated by radiation,repairing cell DNA damage caused by radiation,and reducing radiation-induced programmed necrosis and death of intestinal cells.In addition,the development of nanomedicine strategies for radiation-induced intestinal injury protection should avoid the potential toxicity caused by complex synthesis processes.
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