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Intratumoral injection of hydrogel-embedded nanoparticles enhances retention in glioblastoma
Nanoscale ( IF 5.8 ) Pub Date : 2020-11-25 , DOI: 10.1039/d0nr05053a Giulia Brachi 1 , Javier Ruiz-Ramírez , Prashant Dogra , Zhihui Wang , Vittorio Cristini , Gianluca Ciardelli , Robert C Rostomily , Mauro Ferrari , Andrei M Mikheev , Elvin Blanco , Clara Mattu
Nanoscale ( IF 5.8 ) Pub Date : 2020-11-25 , DOI: 10.1039/d0nr05053a Giulia Brachi 1 , Javier Ruiz-Ramírez , Prashant Dogra , Zhihui Wang , Vittorio Cristini , Gianluca Ciardelli , Robert C Rostomily , Mauro Ferrari , Andrei M Mikheev , Elvin Blanco , Clara Mattu
Affiliation
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Intratumoral drug delivery is a promising approach for the treatment of glioblastoma multiforme (GBM). However, drug washout remains a major challenge in GBM therapy. Our strategy, aimed at reducing drug clearance and enhancing site-specific residence time, involves the local administration of a multi-component system comprised of nanoparticles (NPs) embedded within a thermosensitive hydrogel (HG). Herein, our objective was to examine the distribution of NPs and their cargo following intratumoral administration of this system in GBM. We hypothesized that the HG matrix, which undergoes rapid gelation upon increases in temperature, would contribute towards heightened site-specific retention and permanence of NPs in tumors. BODIPY-containing, infrared dye-labeled polymeric NPs embedded in a thermosensitive HG (HG–NPs) were fabricated and characterized. Retention and distribution dynamics were subsequently examined over time in orthotopic GBM-bearing mice. Results demonstrate that the HG–NPs system significantly improved site-specific, long-term retention of both NPs and BODIPY, with co-localization analyses showing that HG–NPs covered larger areas of the tumor and the peri-tumor region at later time points. Moreover, NPs released from the HG were shown to undergo uptake by surrounding GBM cells. Findings suggest that intratumoral delivery with HG–NPs has immense potential for GBM treatment, as well as other strategies where site-specific, long-term retention of therapeutic agents is warranted.
中文翻译：
瘤内注射水凝胶嵌入纳米粒子可增强胶质母细胞瘤中的保留
瘤内给药是治疗多形性胶质母细胞瘤（GBM）的一种有前途的方法。然而，药物清除仍然是 GBM 治疗中的一个主要挑战。我们的策略旨在减少药物清除并提高特定位点的停留时间，涉及对由嵌入热敏水凝胶（HG）内的纳米颗粒（NP）组成的多组分系统进行局部管理。在此，我们的目标是检查 GBM 中该系统瘤内给药后 NP 及其货物的分布。我们假设，HG 基质在温度升高时会快速凝胶化，有助于增强纳米颗粒在肿瘤中的位点特异性保留和持久性。制备并表征了嵌入热敏 HG（HG-NP）中的含 BODIPY 的红外染料标记的聚合物纳米颗粒。随后，随着时间的推移，在原位携带 GBM 的小鼠中检查了保留和分布动态。结果表明，HG-NPs 系统显着改善了 NPs 和 BODIPY 的位点特异性、长期保留，共定位分析表明 HG-NPs 在稍后的时间点覆盖了更大的肿瘤区域和肿瘤周围区域。此外，从 HG 释放的 NP 被周围 GBM 细胞吸收。研究结果表明，HG-NPs 的瘤内递送对于 GBM 治疗以及需要在特定部位长期保留治疗药物的其他策略具有巨大潜力。
更新日期：2020-11-25
中文翻译：
瘤内注射水凝胶嵌入纳米粒子可增强胶质母细胞瘤中的保留
瘤内给药是治疗多形性胶质母细胞瘤（GBM）的一种有前途的方法。然而，药物清除仍然是 GBM 治疗中的一个主要挑战。我们的策略旨在减少药物清除并提高特定位点的停留时间，涉及对由嵌入热敏水凝胶（HG）内的纳米颗粒（NP）组成的多组分系统进行局部管理。在此，我们的目标是检查 GBM 中该系统瘤内给药后 NP 及其货物的分布。我们假设，HG 基质在温度升高时会快速凝胶化，有助于增强纳米颗粒在肿瘤中的位点特异性保留和持久性。制备并表征了嵌入热敏 HG（HG-NP）中的含 BODIPY 的红外染料标记的聚合物纳米颗粒。随后，随着时间的推移，在原位携带 GBM 的小鼠中检查了保留和分布动态。结果表明，HG-NPs 系统显着改善了 NPs 和 BODIPY 的位点特异性、长期保留，共定位分析表明 HG-NPs 在稍后的时间点覆盖了更大的肿瘤区域和肿瘤周围区域。此外，从 HG 释放的 NP 被周围 GBM 细胞吸收。研究结果表明，HG-NPs 的瘤内递送对于 GBM 治疗以及需要在特定部位长期保留治疗药物的其他策略具有巨大潜力。
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