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与京尼平交联的大孔壳聚糖/海藻酸盐水凝胶会聚集并保留胶质母细胞瘤癌细胞。

Macroporous chitosan/alginate hydrogels crosslinked with genipin accumulate and retain glioblastoma cancer cells.

作者信息

Parès Lauriane, Naasri Sahar, Delattre Lisa, Therriault Hélène, Liberelle Benoît, De Crescenzo Gregory, Lauzon Marc-Antoine, Faucheux Nathalie, Paquette Benoit, Virgilio Nick

机构信息

Research Center for High Performance Polymer and Composite Systems (CREPEC), Department of Chemical Engineering, Polytechnique Montréal Montréal H3C 3A7 Québec Canada

Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke Sherbrooke J1H 5N4 Québec Canada

出版信息

RSC Adv. 2024 Nov 5;14(48):35286-35304. doi: 10.1039/d4ra06197g. eCollection 2024 Nov 4.

DOI:10.1039/d4ra06197g
PMID:39502176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11537210/
Abstract

Grade IV multiforme glioblastoma (GBM) is an aggressive cancer that remains incurable due to the GBM cells invading and proliferating in the surrounding healthy tissues, even after tumor resection. A new therapeutic paradigm to treat GBM is to attract and accumulate GBM cells in a macroporous hydrogel inserted in the surgical cavity after tumor resection, followed by a targeted high dose of radiotherapy. This work presents a molding-based method to prepare macroporous hydrogels composed of sodium alginate and chitosan, homogeneously mixed in solution using sodium bicarbonate, and subsequently crosslinked with genipin and calcium chloride. The gels display a blue color, the result of chitosan crosslinking with genipin, fully interconnected pores with an average diameter of 180 μm (and tunable over a wide range), with a compression modulus of 10 kPa, close to the value of brain tissues. The gels are stable in cell culture media and keep their integrity after radiation doses comparable to current GBM treatment levels. Finally, F98 GBM cells accumulate relatively homogeneously and are retained within the gels.

摘要

四级多形性胶质母细胞瘤（GBM）是一种侵袭性癌症，即使在肿瘤切除后，由于GBM细胞在周围健康组织中侵袭和增殖，仍然无法治愈。一种治疗GBM的新治疗模式是在肿瘤切除后，将GBM细胞吸引并聚集在插入手术腔的大孔水凝胶中，然后进行靶向高剂量放疗。这项工作提出了一种基于成型的方法来制备由海藻酸钠和壳聚糖组成的大孔水凝胶，它们在溶液中使用碳酸氢钠均匀混合，随后用京尼平（genipin）和氯化钙交联。凝胶呈现蓝色，这是壳聚糖与京尼平交联的结果，具有平均直径为180μm（且在很宽范围内可调）的完全相互连通的孔，压缩模量为10kPa，接近脑组织的值。凝胶在细胞培养基中稳定，在与当前GBM治疗水平相当的辐射剂量后保持其完整性。最后，F98 GBM细胞相对均匀地聚集并保留在凝胶内。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/825006f3a982/d4ra06197g-f13.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/825006f3a982/d4ra06197g-f13.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/037db0d71b07/d4ra06197g-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/6fa4b0f610a9/d4ra06197g-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/7ddb2a2fac7d/d4ra06197g-f10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aff/11537210/825006f3a982/d4ra06197g-f13.jpg

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