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Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

机译：组织蛋白酶B可降解，NIR响应纳米颗粒平台，用于靶特异性癌症治疗

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Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.
机译：刺激响应性抗癌配方可以促进靶肿瘤内的药物释放和活化，促进细胞摄取，以及提高药物的治疗效果，降低偏移效应。在本作工作中，开发并表征吲哚菁绿（ICG）聚谷氨酸（PGA）纳米颗粒。用组织蛋白酶B消化纳米粒子，在晚期肿瘤的微环境中过表达的基质金属蛋白酶，降低粒度和ICG细胞摄取增加。在PGA纳米粒子中掺入ICG在组织蛋白酶B存在下，具有时间依赖性改变的光学性质的NIR吸收剂。具有最小的暗毒性，在NIR暴露时，制剂表现出显着的细胞毒性。结合配方用Saporin，一种核糖体灭活蛋白质，导致协同增强的细胞毒性，归因于Endo /溶酶体的光泌素的光素释放。结果表明，这种治疗方法可以在治疗浅表性恶性肿瘤时提供显着的治疗益处，例如头部和颈部肿瘤。

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