目的 提取稳定的生物合成纳米级气泡(BNBs),并研究BNBs在小鼠体内的安全性,为BNBs作为超声造影剂等临床应用提供理论支撑.方法 培养嗜盐古菌获得性质均一稳定的BNBs,并通过聚乙二醇(PEG)修饰降低BNBs的免疫原性.选用16只9周龄健康雄性小鼠,随机分为2组,每组8只,实验组按每3 d 1次尾静脉注射PEG修饰后的BNBs,共计注射3次,对照组按相同频率注射等剂量磷酸盐缓冲液(PBS).分别于实验开始前、每次注射完2 d后记录所有小鼠的体重,在最后一次注射完成后采集小鼠血液进行生化分析,观察小鼠的行为和精神状态,并取主要器官进行组织切片观察.结果 成功筛选出BNBs并完成PEG修饰,实验组和对照组小鼠在体重变化和生化指标结果上差异无统计学意义(P＞0.05),实验组小鼠未出现精神和行为异常,各组织切片未见病理损伤.结论 PEG修饰的BNBs生产工艺简单,易于推广,在小鼠体内具有一定的生物安全性,为BNBs作为超声造影剂和其他临床应用提供了前期基础.
Extraction of biosynthetic nanobubbles and there in vivo biosafety evaluation in mice
Objective The aim of this study is to isolate stable biosynthetic nanobubbles(BNBs)for safety evaluation in mice,with the ultimate goal of supporting the use of BNBs as ultrasound contrast agents and in various clinical applications.Methods Halophilic archaea were cultured to produce consistently stable BNBs,with their immunogenicity reduced by polyethylene glycol(PEG)modification.Sixteen healthy male mice,9 weeks old,were randomly assigned into 2 groups of 8 mice each.The experimental group received injections of PEG-modified BNBs every 3 days via the tail vein for a total of 3 injections,while the control group received phosphate buffer solution(PBS)at the same intervals.Body weights were measured before the experiment and 2 days after each injection.Following the final injection,blood samples were collected for biochemical analysis,and the mice's behavior,mental state,and organ tissues were examined using histological slices.Results BNBs were successfully screened and PEG-modified.There were no significant differences in body weight changes and biochemical indicators between the experimental and control groups(P＞0.05).Mice in the experimental group exhibited no abnormal behavior or mental status,and histological analysis of various tissues showed no pathological damage.Conclusions PEG-modified BNBs have a straightforward and easily scalable production process,showing a certain level of biosafety in mice.This sets the stage for their potential use as ultrasound contrast agents and in various clinical applications.
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