我们报道了一种可注射的树枝状聚合物水凝胶（DH）的成功合成，该水凝胶携带有美法仑，一种用于视网膜母细胞瘤治疗的临床药物，有结合形式和游离形式。聚酰胺胺 (PAMAM) 树枝状大分子第 5 代 (G5) 使用酸敏感的缩醛-二苯并环辛炔接头进行表面修饰，然后与美法仑-PEG-N3 缀合物进行叠氮-炔环加成，形成 G5-缩醛-美法仑。在 G5-缩醛-美法仑和 PEG-二丙烯酸酯之间的 DH 凝胶化过程中，添加游离美法仑，形成携带缀合和游离形式药物的水凝胶（G5-缩醛-美法仑-DH/美法仑）。马法兰从 G5-缩醛-马法兰-DH/马法兰中缓慢释放，由于酸触发的缩醛键断裂，结合的马法兰在 pH 5.3 时释放得更快。该制剂的体外安全性和有效性是在人角膜上皮细胞 (HCE-2) 和视网膜母细胞瘤细胞 (Y79) 上建立的。在视网膜母细胞瘤体内 Y79 肿瘤异种移植模型中，瘤内注射 G5-美法仑-DH 制剂可延长肿瘤抑制时间。这种可注射、多模式、pH 响应型制剂显示出玻璃体内注射治疗视网膜母细胞瘤的前景。

We report the successful synthesis of an injectable dendrimer hydrogel (DH) carrying melphalan, a clinical drug for retinoblastoma treatment, in both conjugated and free forms. Polyamidoamine (PAMAM) dendrimer generation 5 (G5) is surface-modified with an acid-sensitive acetal-dibenzocyclooctyne linker and then undergoes azide-alkyne cycloaddition with melphalan-PEG-N3 conjugate to form G5-acetal-melphalan. During the DH gelation between G5-acetal-melphalan and PEG-diacrylate, free melphalan is added, resulting in a hydrogel (G5-acetal-melphalan-DH/melphalan) that carries the drug in both conjugated and free forms. Melphalan is slowly released from G5-acetal-melphalan-DH/melphalan, with the conjugated melphalan released more quickly at pH 5.3 due to acid-triggered acetal bond cleavage. The formulation's in vitro safety and efficacy were established on human corneal epithelia (HCE-2) and retinoblastoma cells (Y79). In an in vivo Y79 tumor xenograft model of retinoblastoma, intratumorally injected G5-melphalan-DH formulation prolonged tumor suppression. This injectable, multimodal, pH-responsive formulation shows promise for intravitreal injection to treat retinoblastoma.