Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule.
Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule.
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DOI：
10.3390/pharmaceutics14030667
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发表时间：
2022-03-18
期刊：
影响因子：
5.4
通讯作者：
Celli J
中科院分区：
文献类型：
--
作者：
Petrovic LZ;Oumano M;Hanlon J;Arnoldussen M;Koruga I;Yasmin-Karim S;Ngwa W;Celli J
金纳米颗粒（GNP）已显示出作为放射增敏剂和作为补充药物递送剂以改善癌症治疗中的治疗指数的特别前景。然而，最佳实施方式关键取决于GNP在照射时的定位，这反过来又取决于它们的大小、形状和化学功能化，以及生物体水平的药代动力学和与肿瘤微环境的相互作用。在这里，我们使用A549肺癌细胞的体外3D培养物，其重现与细胞外基质（ECM）组分的相互作用，结合定量荧光成像来研究超小GNP在肿瘤和ECM中的时间依赖性定位如何影响对肿瘤细胞的损伤增强程度。荧光标记的GNP在3D培养物中的共聚焦成像显示，纳米颗粒最初嵌入ECM中，并且仅在多天内逐渐积累在癌细胞中。此外，GNP从ECM重新分布到细胞区室的时机直接影响功效，当GNP在3D肿瘤结节中显著积累后进行照射时，损伤增强。这些结果强调了治疗计划中的时机和时间安排的重要性，以确保最佳的放射增敏，以及在重现肿瘤微环境相互作用要素的模型系统中研究这些效应的必要性。
Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on their size, shape, and chemical functionalization, as well as organism-level pharmacokinetics and interactions with the tumor microenvironment. Here, we use in vitro 3D cultures of A549 lung carcinoma cells, which recapitulate interaction with extracellular matrix (ECM) components, combined with quantitative fluorescence imaging to study how time-dependent localization of ultrasmall GNPs in tumors and ECM impacts the degree of damage enhancement to tumor cells. Confocal imaging of fluorescence-labeled GNPs in 3D culture reveals that nanoparticles are initially embedded in ECM and only gradually accumulate in cancer cells over multiple days. Furthermore, the timing of GNP redistribution from ECM to cellular compartments directly impacts efficacy, with major damage enhancement when irradiation is performed after GNPs have accumulated significantly in 3D tumor nodules. These results underscore the importance of the timing and scheduling in treatment planning to ensure optimal radiosensitization, as well as the necessity of studying these effects in model systems that recapitulate elements of tumor microenvironment interaction.
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影响因子：
12.4
作者：
Glidden MD;Celli JP;Massodi I;Rizvi I;Pogue BW;Hasan T
通讯作者：
Hasan T
影响因子：
3.5
作者：
Hao Y;Altundal Y;Moreau M;Sajo E;Kumar R;Ngwa W
通讯作者：
Ngwa W
影响因子：
17.1
作者：
Huang K;Ma H;Liu J;Huo S;Kumar A;Wei T;Zhang X;Jin S;Gan Y;Wang PC;He S;Zhang X;Liang XJ
通讯作者：
Liang XJ
影响因子：
4.7
作者：
Moreau M;Yasmin-Karim S;Kunjachan S;Sinha N;Gremse F;Kumar R;Chow KF;Ngwa W
通讯作者：
Ngwa W
影响因子：
4.6
作者：
McQuaid HN;Muir MF;Taggart LE;McMahon SJ;Coulter JA;Hyland WB;Jain S;Butterworth KT;Schettino G;Prise KM;Hirst DG;Botchway SW;Currell FJ
通讯作者：
Currell FJ