Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection. When dispersed in aqueous solution, the designed CPT prodrug spontaneously assembles into supramolecular filaments with a 100% CPT loading. In both in vitro and ex vivo assays, we show that the designed CPT prodrug can be steadily released from its supramolecular filament hydrogel, effectively killing primary GBM cells derived from patients. We also found that the solution containing self-assembling CPT filaments can be directly applied to the tumor cavity after surgical removal, and forms a gel immediately upon contact with the brain tissue. Our in vivo studies with a resection and recurrence mouse model suggest that this prodrug hydrogel can release cancer therapeutics into brain parenchyma over a long period of time, suppressing tumor recurrence and leading to prolonged survival. We believe that the simplicity in prodrug design and the high efficacy in suppressing GBM growth enable the unique potential of this SAPD hydrogels for clinical translation as an adjunct therapy for GBM treatment.

中文翻译：

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自组装和自配制的前药水凝胶仪可延长胶质母细胞瘤切除和复发模型的生存期。

多形胶质母细胞瘤（GBM）是最常见和最具破坏性的原发性脑癌。尽管进行了外科手术和化学/放射疗法，但经常会复发并导致患者死亡。我们在此报告基于喜树碱（CPT）的自组装前药（SAPD）水凝胶的发展，该凝胶可用作最大肿瘤切除术后GBM的局部治疗的辅助治疗。当分散在水溶液中时，设计的CPT前药会自发组装成100％CPT负载的超分子长丝。在体外和离体试验中，我们都表明设计的CPT前药可以从其超分子细丝水凝胶中稳定释放，有效杀死源自患者的原代GBM细胞。我们还发现，含有自组装CPT细丝的溶液可在手术切除后直接应用于肿瘤腔，并在与脑组织接触后立即形成凝胶。我们对切除和复发小鼠模型的体内研究表明，这种前药水凝胶可以在很长一段时间内将癌症治疗剂释放到脑实质中，从而抑制肿瘤复发并延长生存期。我们相信，前药设计的简便性和抑制GBM增长的高效性使这种SAPD水凝胶具有独特的潜力，可作为临床翻译作为GBM治疗的辅助疗法。我们对切除和复发小鼠模型的体内研究表明，这种前药水凝胶可以在很长一段时间内将癌症治疗剂释放到脑实质中，从而抑制肿瘤复发并延长生存期。我们相信，前药设计的简便性和抑制GBM增长的高效性使这种SAPD水凝胶具有独特的潜力，可作为临床翻译作为GBM治疗的辅助疗法。我们对切除和复发小鼠模型的体内研究表明，这种前药水凝胶可在很长一段时间内将癌症治疗剂释放到脑实质中，从而抑制肿瘤复发并延长生存期。我们相信，前药设计的简便性和抑制GBM增长的高效性使这种SAPD水凝胶具有独特的潜力，可作为临床翻译作为GBM治疗的辅助疗法。