Magnetic Targeting and Ultrasound Activation of Liposome-Microbubble Conjugate for Enhanced Delivery of Anticancer Therapies
Magnetic Targeting and Ultrasound Activation of Liposome-Microbubble Conjugate for Enhanced Delivery of Anticancer Therapies
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DOI：
10.1021/acsami.0c05308
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发表时间：
2020-05-27
影响因子：
9.5
通讯作者：
Xu, Ronald
中科院分区：
文献类型：
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作者：
Dwivedi, Pankaj;Kiran, Sonia;Xu, Ronald
以最小的毒性和最大的结果有效地递送化学治疗剂在临床上是重要的，但在技术上具有挑战性。在这里，我们合成了一种复合物的阿霉素（DOX）-负载磁脂质体（DOX-ML）微泡（DOX-ML-MB）的磁响应和超声敏感的抗癌治疗，提高效率的交付。合成了6.8 +/- 1.36 nm的柠檬酸盐稳定的氧化铁纳米颗粒（MN），在172 +/- 9.2 nm的寡层囊泡的核心中负载有DOX，并与全氟化碳（PFC）气体负载的微泡共价缀合以形成类似于4 μ m的DOX-ML-MB。DOX-ML-MB表现出显著的磁性，并且能够在暴露于超声（US）脉冲时立即释放化疗剂和DOX-ML。体外研究表明，DOX-ML-MB在US脉冲存在下促进细胞凋亡，并且即使在低剂量下也高度有效地杀死BxPc-3和Panc 02胰腺癌细胞。在裸鼠的胰腺癌异种移植模型中，与对照组相比，在静脉内施用DOX-ML-MB后观察到肿瘤体积的显著减小。在US刺激的存在下，清楚地观察到在整个磁靶向肿瘤组织中深深穿透的氧化铁纳米颗粒。我们的研究证明了使用DOX-ML-MB进行位点特异性靶向和药物控释的潜力。它为胰腺癌和其他组织恶性肿瘤的治疗开辟了一条新的途径，其中需要精确递送治疗药物。
Effective delivery of chemotherapeutics with minimal toxicity and maximal outcome is clinically important but technically challenging. Here, we synthesize a complex of doxorubicin (DOX)-loaded magneto-liposome (DOX-ML) microbubbles (DOX-ML-MBs) for magnetically responsive and ultrasonically sensitive delivery of anticancer therapies with enhanced efficiency. Citrate-stabilized iron oxide nanoparticles (MNs) of 6.8 +/- 1.36 nm were synthesized, loaded with DOX in the core of oligolamellar vesicles of 172 +/- 9.2 nm, and covalently conjugated with perfluorocarbon (PFC)-gas-loaded microbubbles to form DOX-ML-MBs of similar to 4 mu m. DOX-ML-MBs exhibited significant magnetism and were able to release chemotherapeutics and DOX-MLs instantly upon exposure to ultrasound (US) pulses. In vitro studies showed that DOX-ML-MBs in the presence of US pulses promoted apoptosis and were highly effective in killing both BxPc-3 and Panc02 pancreatic cancer cells even at a low dose. Significant reduction in the tumor volume was observed after intravenous administration of DOX-ML-MBs in comparison to the control group in a pancreatic cancer xenograft model of nude mice. Deeply penetrated iron oxide nanoparticles throughout the magnetically targeted tumor tissues in the presence of US stimulation were clearly observed. Our study demonstrated the potential of using DOX-ML-MBs for site-specific targeting and controlled drug release. It opens a new avenue for the treatment of pancreatic cancer and other tissue malignancies where precise delivery of therapeutics is necessary.