Hydrogel Microtumor Arrays to Evaluate Nanotherapeutics.
Hydrogel Microtumor Arrays to Evaluate Nanotherapeutics.
复制标题
用于评估纳米疗法的水凝胶微肿瘤阵列。
DOI：
10.1002/adhm.202201696
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发表时间：
2023
影响因子：
10
通讯作者：
Kilian,KristopherA
中科院分区：
文献类型：
--
作者：
Liu,Yiling;Nemec,Stephanie;Kopecky,Chantal;Stenzel,MartinaH;Kilian,KristopherA
纳米粒制剂具有靶向选择性好、无全身毒性、给药后肿瘤微环境药物浓度增加等优点，在肿瘤治疗中具有许多优势。然而，纳米医学的前景受到临床前模型的限制，这些模型在进入人体试验之前未能准确评估新药。在这项工作中，展示了一种使用通过水凝胶微图案化形成的微肿瘤阵列来测试纳米药物的新方法。这项技术允许在几何图案内划分不同的细胞状态-其中曲率的边界区域启动干细胞样组分-允许以高重复性同时探测不同癌细胞组分的药物摄取和疗效。使用不同转移潜能的黑色素瘤细胞，发现干细胞分数和纳米颗粒摄取之间的关系。形变细胞术显示，干细胞样群表现出更易机械变形的细胞膜。由于肿瘤中的干细胞部分与耐药、复发和转移有关，研究结果表明纳米药物制剂非常适合在癌症治疗中针对这一危险细胞群体。
Nanoparticle drug formulations have many advantages for cancer therapy due to benefits in targeting selectivity, lack of systemic toxicity, and increased drug concentration in the tumor microenvironment after delivery. However, the promise of nanomedicine is limited by preclinical models that fail to accurately assess new drugs before entering human trials. In this work a new approach to testing nanomedicine using a microtumor array formed through hydrogel micropatterning is demonstrated. This technique allows partitioning of heterogeneous cell states within a geometric pattern—where boundary regions of curvature prime the stem cell‐like fraction—allowing to simultaneously probe drug uptake and efficacy in different cancer cell fractions with high reproducibility. Using melanoma cells of different metastatic potential, a relationship between stem fraction and nanoparticle uptake is discovered. Deformation cytometry reveals that the stem cell‐like population exhibits a more mechanically deformable cell membrane. Since the stem fraction in a tumor is implicated in drug resistance, recurrence, and metastasis, the findings suggest that nanoparticle drug formulations are well suited for targeting this dangerous cell population in cancer therapy.