Politecnico di Torino, DIMEAS, C.so Duca degli Abruzzi 24, 10129 Torino, Italy.
Nanoscale. 2020 Dec 8;12(46):23838-23850. doi: 10.1039/d0nr05053a.
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.
瘤内药物递送是治疗多形性胶质母细胞瘤（GBM）的一种很有前途的方法。然而，药物清除仍然是 GBM 治疗的一个主要挑战。我们的策略旨在减少药物清除并增强药物在特定部位的停留时间，该策略涉及局部给予由嵌入在温敏水凝胶（HG）中的纳米颗粒（NPs）组成的多组分系统。在此，我们的目的是研究该系统在 GBM 中的瘤内给药后 NPs 及其货物的分布情况。我们假设，HG 基质在温度升高时会迅速胶凝，这将有助于增加 NPs 在肿瘤中的特定部位保留和持久性。制备并表征了含有 BODIPY 的、红外染料标记的聚合物 NPs 嵌入在温敏 HG（HG-NPs）中。随后在荷 GBM 原位模型的小鼠中随时间研究了保留和分布动力学。结果表明，HG-NPs 系统显著提高了 NPs 和 BODIPY 的特定部位、长期保留率，共定位分析表明，HG-NPs 在后期覆盖了更大的肿瘤和肿瘤周围区域。此外，从 HG 释放的 NPs 被证明被周围的 GBM 细胞摄取。这些发现表明，HG-NPs 的瘤内给药具有巨大的 GBM 治疗潜力，以及其他需要特定部位、长期保留治疗剂的策略。
