Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo.
Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo.
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DOI：
10.1080/10717544.2021.1895907
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发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Osaki T
中科院分区：
文献类型：
--
作者：
Yokoe I;Omata D;Unga J;Suzuki R;Maruyama K;Okamoto Y;Osaki T
聚乙二醇化阿霉素脂质体(PLD)是一种具有代表性的纳米药物，可提高肿瘤的选择性和安全性。然而，在临床医学上，PLD相对于传统阿霉素的治疗优势并不显著。微泡和超声联合治疗是一种通过改善药物传递来增强化疗药物抗肿瘤效果的有前途的策略。最近，几项临床前研究表明，脂泡(LBS)与低强度超声(LIUS)相结合具有药物输送潜力。本研究旨在阐明LBS和LIUS联合应用是否能增强PLD在同基因小鼠肿瘤模型中的积聚和抗肿瘤作用。使用LBS的对比增强超声成像显示，LUS后对比度增强显著降低，这表明LUS暴露导致肿瘤组织中LBS的破坏。定量评估显示，联合使用LBS和LUS可改善PLD在肿瘤内的蓄积。此外，PLD、LBS和LIUS联合治疗可抑制肿瘤生长。因此，LBS和LIUS联合使用通过增加PLD在肿瘤组织中的积聚来增强PLD的抗肿瘤作用。综上所述，本研究提供了重要证据，证明LBS和LIUS联合应用是提高PLD瘤内给药和体内抗肿瘤作用的有效方法。
Pegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles and ultrasound (US) is a promising strategy for enhancing the antitumor effects of chemotherapeutics by improving drug delivery. Recently, several preclinical studies have shown the drug delivery potential of lipid bubbles (LBs), newly developed monolayer microbubbles, in combination with low-intensity US (LIUS). This study aimed to elucidate whether the combined use of LBs and LIUS enhanced the intratumoral accumulation and antitumor effect of PLD in syngeneic mouse tumor models. Contrast-enhanced US imaging using LBs showed a significant decrease in contrast enhancement after LIUS, indicating that LIUS exposure induced the destruction of LBs in the tumor tissue. A quantitative evaluation revealed that the combined use of LBs and LIUS improved the intratumoral accumulation of PLD. Furthermore, tumor growth was inhibited by combined treatment with PLD, LBs, and LIUS. Therefore, the combined use of LBs and LIUS enhanced the antitumor effect of PLD by increasing its accumulation in the tumor tissue. In conclusion, the present study provides important evidence that the combination of LBs and LIUS is an effective method for enhancing the intratumoral delivery and antitumor effect of PLD in vivo.
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影响因子：
4.6
作者：
Egawa, Gyohei;Nakamizo, Satoshi;Natsuaki, Yohei;Doi, Hiromi;Miyachi, Yoshiki;Kabashima, Kenji
通讯作者：
Kabashima, Kenji
影响因子：
5.6
作者：
Paefgen V;Doleschel D;Kiessling F
通讯作者：
Kiessling F
影响因子：
3.4
作者：
Kudo, Nobuki;Okada, Kengo;Yamamoto, Katsuyuki
通讯作者：
Yamamoto, Katsuyuki
影响因子：
78.5
作者：
Chabner, BA;Roberts, TG
通讯作者：
Roberts, TG
影响因子：
4.5
作者：
Sorace AG;Warram JM;Umphrey H;Hoyt K
通讯作者：
Hoyt K