Perfluoropentane-filled chitosan poly-acrylic acid nanobubbles with high stability for long-term ultrasound imaging in vivo

作者全名："Gao, Xuemei; Guo, Dajing; Mao, Xiang; Shan, Xuefeng; He, Xuemei; Yu, Chaoqun"

作者地址："[Gao, Xuemei; Guo, Dajing] Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Mao, Xiang] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Mao, Xiang] Chongqing Med Univ, Coll Biomed Engn, Chongqing Key Lab Biomed Engn, Chongqing 400016, Peoples R China; [Shan, Xuefeng] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China; [He, Xuemei] Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, Chongqing 400016, Peoples R China; [Yu, Chaoqun] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China"

通信作者："Yu, CQ (corresponding author), Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China."

来源：NANOSCALE

ESI学科分类：PHYSICS

WOS号：WOS:000630384400017

JCR分区：Q1

影响因子：6.7

年份：2021

卷号：13

期号：10

开始页：5333

结束页：5343

文献类型：Article

关键词：　

摘要："Reducing the size of ultrasound contrast agents (UCAs) will decrease the intensity of the ultrasound echogenic signals and reduce the stability of the bubbles. Therefore, it is a challenge to design nanobubbles that are less than 200 nm in size and that have both good imaging abilities and high stability for long-term imaging in vivo. In this work, we successfully prepared perfluoropentane-filled chitosan poly-acrylic acid (PFP-CS-PAA) nanobubbles with a size of about 100 nm via a direct simple core-template-free strategy. In vitro tests demonstrated that the nanobubbles showed satisfactory imaging capabilities in non-linear harmonic imaging mode and had significantly better stability than commercial Sonovue (R) lipid microbubbles. It was valuable to discover that the prepared PFP-CS-PAA nanobubbles could exhibit good imaging quality in rat livers for 10 min after intravenous injection. Also, the PFP-CS-PAA nanobubbles could maintain imaging capabilities in nude mouse tumors for 7 days after intratumoral injection, which indicated that these nanobubbles could keep their stability for a long time in vivo. To the best of our knowledge, the ultrasound imaging persistence time in vivo was the longest of currently reported polymer nanobubbles that are smaller than 200 nm. This new nanosized UCA with high stability has great potential for long-term ultrasound imaging in vivo. Tumor cellular uptake and histological analysis revealed that PFP-CS-PAA nanobubbles could be taken up into tumor cells, but no intracellular uptake was observed in the case of Sonovue (R). Animal fluorescence imaging in vivo demonstrated that PFP-CS-PAA nanobubbles could be effectively cleared after intravenous injection within 168 h. MTT assays indicated that PFP-CS-PAA nanobubbles had appropriate biocompatibility. Abnormal levels of blood urea nitrogen were detected after the intravenous administration of PFP-CS-PAA nanobubbles to rats, and body-weight gain was inhibited for up to 6 d, but, after that, body weights recovered their tendency to increase."

基金机构：National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81401424]

基金资助正文：We greatly acknowledge financial support from the National Natural Science Foundation of China (NSFC) under Grant No. 81401424.