Penetrative and Sustained Drug Delivery Using Injectable Hydrogel Nanocomposites for Postsurgical Brain Tumor Treatment
Penetrative and Sustained Drug Delivery Using Injectable Hydrogel Nanocomposites for Postsurgical Brain Tumor Treatment
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DOI：
10.1021/acsnano.2c10094
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发表时间：
2023-03-16
期刊：
影响因子：
17.1
通讯作者：
Choi, Seung Hong
中科院分区：
文献类型：
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作者：
Kang, Taegyu;Cha, Gi Doo;Choi, Seung Hong
多形性胶质母细胞瘤（GBM）的术后全身化疗和放疗往往是无效的。肿瘤细胞深入脑实质是根除GBM的重要障碍。在这里，我们提出了一个潜在的解决方案，这一挑战，通过引入可注射的温敏水凝胶纳米复合材料。作为一种含有载药胶束和水分散性亚铁磁性氧化铁纳米立方体（wFIONs）的液体溶液，水凝胶纳米复合材料在手术后被注射到切除的肿瘤部位。它在体温下迅速凝胶化，作为一个柔软的、深层的皮质内药物储存库。载药胶束靶向残留的GBM细胞，并以最小的过早释放递送药物。交变磁场通过wFION产生的热量加速扩散，从而实现穿透式药物递送。在原位小鼠GBM模型中证明了显著抑制的肿瘤生长和改善的存活率。我们的系统证明了水凝胶纳米复合材料平台用于手术后GBM治疗的潜力。
Postsurgical treatment of glioblastoma multiforme (GBM) by systemic chemotherapy and radiotherapy is often inefficient. Tumor cells infiltrating deeply into the brain parenchyma are significant obstacles to the eradication of GBM. Here, we present a potential solution to this challenge by introducing an injectable thermoresponsive hydrogel nanocomposite. As a liquid solution that contains drug-loaded micelles and water-dispersible ferrimagnetic iron oxide nanocubes (wFIONs), the hydrogel nanocomposite is injected into the resected tumor site after surgery. It promptly gelates at body temperature to serve as a soft, deep intracortical drug reservoir. The drug loaded micelles target residual GBM cells and deliver drugs with a minimum premature release. Alternating magnetic fields accelerate diffusion through heat generation from wFIONs, enabling penetrative drug delivery. Significantly suppressed tumor growth and improved survival rates are demonstrated in an orthotopic mouse GBM model. Our system proves the potential of the hydrogel nanocomposite platform for postsurgical GBM treatment.