Local presentation of cancer drugs by injectable drug-eluting depots reduces systemic side effects and improves efficacy. However, local depots deplete their drug stores and are difficult to introduce into stiff tissues, or organs, such as the brain, that cannot accommodate increased pressure. We present a method for introducing targetable depots through injection of activated ester molecules into target tissues that react with and anchor themselves to the local extracellular matrix (ECM) and subsequently capture systemically administered small molecules through bioorthogonal click chemistry. A computational model of tissue-anchoring depot formation and distribution was verified by histological analysis and confocal imaging of cleared tissues. ECM-anchored click groups do not elicit any noticeable local or systemic toxicity or immune response and specifically capture systemically circulating molecules at intradermal, intratumoral, and intracranial sites for multiple months. Taken together, ECM anchoring of click chemistry motifs is a promising approach to specific targeting of both small and large therapeutics, enabling repeated local presentation for cancer therapy and other diseases.

中文翻译：

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用于特定组织靶向的细胞外基质锚定点击图案。

通过注射药物洗脱贮库局部呈现抗癌药物可减少全身副作用并提高疗效。然而，局部药库耗尽了它们的药物储备，并且难以引入僵硬的组织或器官，例如大脑，无法适应增加的压力。我们提出了一种通过将活化的酯分子注射到目标组织中来引入可靶向库的方法，这些组织与局部细胞外基质 (ECM) 发生反应并锚定在局部细胞外基质 (ECM) 上，然后通过生物正交点击化学捕获全身给药的小分子。通过组织学分析和清除组织的共聚焦成像验证了组织锚定库形成和分布的计算模型。ECM 锚定的点击组不会引起任何明显的局部或全身毒性或免疫反应，并在数月内在皮内、肿瘤内和颅内部位特异性地捕获全身循环分子。综上所述，点击化学基序的 ECM 锚定是一种有前途的方法，可以特异性靶向小型和大型疗法，使癌症治疗和其他疾病的重复局部呈现成为可能。