Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study.
Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study.
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DOI：
10.3390/pharmaceutics15061585
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发表时间：
2023-05-24
期刊：
影响因子：
5.4
通讯作者：
Allen IC
中科院分区：
文献类型：
--
作者：
Imran KM;Tintera B;Morrison HA;Tupik JD;Nagai-Singer MA;Ivester H;Council-Troche M;Edwards M;Coutermarsh-Ott S;Byron C;Clark-Deener S;Uh K;Lee K;Boulos P;Rowe C;Coviello C;Allen IC
胰腺肿瘤由于间质液压力高、间质致密和脉管系统紊乱而对药物渗透有抵抗力。超声空化是一种新兴的技术，可以克服许多这些限制。低强度超声波，加上共同管理的空化核组成的气体稳定亚微米级SonoTran颗粒，是有效的增加治疗性抗体递送到异种移植物侧腹肿瘤在小鼠模型。在这里，我们试图使用模拟人类胰腺癌患者的大型动物模型来评估这种方法的有效性。免疫功能低下的猪在胰腺的靶向区域中手术植入人Panc-1胰腺导管腺癌（PDAC）肿瘤。发现这些肿瘤重现了人PDAC肿瘤的许多特征。给动物静脉注射常用的癌症治疗剂西妥昔单抗、吉西他滨和紫杉醇，然后输注SonoTran颗粒。用聚焦超声靶向每只动物中的选定肿瘤以诱导空化。空化使西妥昔单抗、吉西他滨和紫杉醇的肿瘤内浓度分别增加了477%、148%和193%，与相同动物中未使用超声靶向的肿瘤相比。总之，这些数据表明，超声介导的空化，当与气体截留颗粒组合递送时，在临床相关条件下改善胰腺肿瘤中的治疗递送。
Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
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影响因子：
4.6
作者：
Hendricks-Wenger A;Aycock KN;Nagai-Singer MA;Coutermarsh-Ott S;Lorenzo MF;Gannon J;Uh K;Farrell K;Beitel-White N;Brock RM;Simon A;Morrison HA;Tuohy J;Clark-Deener S;Vlaisavljevich E;Davalos RV;Lee K;Allen IC
通讯作者：
Allen IC
兽医患者的临床前动物模型和自发性肿瘤的组织疗法消融：综述。
DOI：
10.1109/tuffc.2021.3110083
发表时间：
2022-01
期刊：
IEEE transactions on ultrasonics, ferroelectrics, and frequency control
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Bear AS;Vonderheide RH;O'Hara MH
通讯作者：
O'Hara MH
影响因子：
51.1
作者：
通讯作者：
--
DOI：
10.4297/najms.2011.31
发表时间：
2011-01
期刊：
North American journal of medical sciences
影响因子：
--
作者：
Andrén-Sandberg A
通讯作者：
Andrén-Sandberg A