Although cyclodextrin-based renal-clearable nanocarriers have a high potential for clinical translation in targeted cancer therapy, their designs remain to be optimized for tumour retention. Here we report on the design of a tailored structure for renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery. Twenty cyclodextrin derivatives with different charged moieties and spacers are synthesized and screened for colloidal stability. The resulting five candidates are evaluated for biodistribution and an optimized structure is identified. The optimized cyclodextrin shows a high tumour accumulation and is used for delivery of doxorubicin and ulixertinib. Higher tumour accumulation and tumour penetration facilitates tumour elimination. The improved antitumour efficacy is demonstrated in heterotopic and orthotopic colorectal cancer models.

尽管基于环糊精的肾脏可清除纳米载体在靶向癌症治疗中具有很高的临床转化潜力，但其设计仍有待针对肿瘤保留进行优化。在这里，我们报告了用于结直肠癌选择性药物递送的肾可清除两性离子环糊精的定制结构的设计。合成了二十种具有不同带电部分和间隔基的环糊精衍生物，并筛选了其胶体稳定性。对所得的五种候选物进行生物分布评估并确定优化结构。优化后的环糊精具有较高的肿瘤蓄积性，可用于输送阿霉素和乌利克替尼。较高的肿瘤积累和肿瘤渗透有利于肿瘤消除。在异位和原位结直肠癌模型中证明了抗肿瘤功效的提高。