Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles.
Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles.
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DOI：
10.1002/advs.202103745
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Lammers T
中科院分区：
文献类型：
--
作者：
Biancacci I;De Lorenzi F;Theek B;Bai X;May JN;Consolino L;Baues M;Moeckel D;Gremse F;von Stillfried S;El Shafei A;Benderski K;Azadkhah Shalmani A;Wang A;Momoh J;Peña Q;Buhl EM;Buyel J;Hennink W;Kiessling F;Metselaar J;Shi Y;Lammers T
癌症纳米药物依赖于增强的渗透性和保留（EPR）效应，以实现有效的靶位点积累。然而，EPR效应在不同肿瘤类型和癌症患者之间具有高度异质性，并且预计其程度在纳米化疗过程中会动态变化。在这里，作者开始纵向研究EPR对荧光团标记和紫杉醇负载聚合物胶束的单剂量和双剂量纳米治疗的动力学影响。使用计算机断层扫描-荧光分子断层扫描成像，表明纳米药物肿瘤积聚的程度可预测治疗结果。研究还表明，基于EPR的肿瘤蓄积的个体间异质性在治疗期间显著增加，特别是对于更有效的双剂量纳米紫杉烷治疗。此外，对于双剂量胶束治疗，肿瘤蓄积随时间显著增加，从第一次给药时的7%注射剂量/克（ID g-1）增加至第五次给药时的15% ID g-1，有助于更有效地抑制肿瘤生长。这些发现揭示了纳米医学治疗过程中EPR效应的动力学，并证明了在纳米医学治疗预测和临床翻译中使用成像的重要性。使用荧光团标记和紫杉醇负载的聚合物胶束，作者证明：1）在治疗过程中，纳米药物肿瘤蓄积的个体间异质性增加; 2）纳米药物肿瘤蓄积的程度可预测治疗结果; 3）在治疗期间多次成像肿瘤蓄积比在治疗开始时仅成像一次更有利地预测治疗结果。
Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally study the dynamics of the EPR effect upon single‐ and double‐dose nanotherapy with fluorophore‐labeled and paclitaxel‐loaded polymeric micelles. Using computed tomography‐fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR‐based tumor accumulation significantly increases during treatment, especially for more efficient double‐dose nanotaxane therapy. Furthermore, for double‐dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g–1) upon the first administration to 15% ID g–1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation. Using fluorophore‐labeled and paclitaxel‐loaded polymeric micelles, the authors demonstrate that: 1) the interindividual heterogeneity in nanomedicine tumor accumulation increases during the course of treatment; 2) the extent of nanomedicine tumor accumulation is predictive for therapy outcome; and 3) imaging tumor accumulation multiple times during treatment more favorably predicts therapy outcome than imaging just once at the start of therapy.
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影响因子：
16.6
作者：
Pérez-Medina C;Abdel-Atti D;Tang J;Zhao Y;Fayad ZA;Lewis JS;Mulder WJM;Reiner T
通讯作者：
Reiner T
影响因子：
17.1
作者：
Kunjachan S;Gremse F;Theek B;Koczera P;Pola R;Pechar M;Etrych T;Ulbrich K;Storm G;Kiessling F;Lammers T
通讯作者：
Lammers T
影响因子：
11.5
作者：
Ramanathan, Ramesh K.;Korn, Ronald L.;Fitzgerald, Jonathan B.
通讯作者：
Fitzgerald, Jonathan B.
影响因子：
--
作者：
Maeda H
通讯作者：
Maeda H
影响因子：
11.5
作者：
Keam, Susan J.
通讯作者：
Keam, Susan J.