Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.
Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.
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DOI：
10.1371/journal.pone.0102727
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ahmed M
中科院分区：
文献类型：
--
作者：
Moussa M;Goldberg SN;Kumar G;Sawant RR;Levchenko T;Torchilin VP;Ahmed M
确定不同载药纳米载体（胶束和脂质体）对射频消融（RFA）联合纳米药物的递送和治疗效果的影响。使用Fischer 344大鼠（n = 196）。 首先，对单个皮下R3230肿瘤或正常肝脏进行RFA，然后立即给予IV荧光珠接下来，为了研究载体类型对药物效率的影响，将RFA与阿霉素的胶束（20 nm）或脂质体（100 nm）制剂组合（Dox;靶向HIF-1α）或槲皮素（Qu;靶向HSP 70）。动物单独接受RFA，RFA与Lipo-Dox或Mic-Dox（1 mg IV，RFA后15分钟），以及RFA前24小时或RFA后15分钟给予的RFA与Lipo-Qu或Mic-Qu（0.3 mg IV）。RFA后24小时评估肿瘤凝固和HIF-1α或HSP 70表达。第三，评价了RFA联合IV Lipo-Dox、Mic-Dox、Lipo-Qu或Mic-Qu（RFA后15分钟）与单独RFA相比对肿瘤生长和动物终点生存的影响。最后，在4-72小时比较RFA/Lipo-Dox和RFA/Mic-Dox之间的药物摄取。较小的20 nm珠在肿瘤（100 nm/500 nm）和肝脏（100 nm）中具有更大的沉积和更深的组织渗透（p<0.05）。Mic-Dox和Mic-Qu比脂质体制剂更能抑制消融周围HIF-1α或HSP 70边缘厚度（p<0.05）。RFA/Mic-Dox早期（4小时）瘤内多柔比星较高，但RFA/Lipo-Dox在RFA后24-72小时瘤内多柔比星逐渐升高（p<0.04）。RFA/Lipo-Qu和RFA/Mic-Qu之间的肿瘤生长和存活率无差异。然而，与RFA/Mic-Dox相比，RFA/Lipo-Dox导致更高的动物终点存活率（p<0.03）。对于RF消融，较小的颗粒胶束具有上级穿透性和更有效的局部分子调节。然而，更大的长循环脂质体载体可导致随着时间的推移更大的肿瘤内药物积聚和减少的肿瘤生长。因此，不同的载体提供了特定的优势，在制定最佳组合疗法时应考虑这些优势。
To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1α) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg IV, 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg IV). Tumor coagulation and HIF-1α orHSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with IV Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4–72 hr. Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24–72 hr post-RFA (p<0.04). No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03). With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly, different carriers provide specific advantages, which should be considered when formulating optimal combination therapies.
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影响因子：
19.7
作者：
Goldberg, SN;Girnan, GD;Kruskal, JB
通讯作者：
Kruskal, JB
影响因子：
9
作者：
Nijkamp, Maarten W.;van der Bilt, Jarmila D. W.;Rinkes, Inne H. M. Borel
通讯作者：
Rinkes, Inne H. M. Borel
影响因子：
5
作者：
Goldberg, SN;Kamel, IR;Raptopoulos, V
通讯作者：
Raptopoulos, V
影响因子：
3.3
作者：
Poon, Ronnie T. P.;Borys, Nicholas
通讯作者：
Borys, Nicholas
影响因子：
3.6
作者：
Perche, Federico;Torchilin, Vladimir P.
通讯作者：
Torchilin, Vladimir P.