이재영 (충남대학교 약학대학, 현 서울대학교 약학대학) | 한빛사논문 > 한빛사

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충남대학교 약학대학, 현 서울대학교 약학대학

Nat. Nanotechnol., Aug 2023, 18 (8) | https://doi.org/10.1038/s41565-023-01381-8 Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery.

Min-Jun Baek ¹, Duy-Thuc Nguyen ¹, Dahan Kim ¹, So-Yeol Yoo², Sang Min Lee ², Jae-Young Lee ² & Dae-Duk Kim ¹

¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.

²College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.

Corresponding authors : Correspondence to Jae-Young Lee or Dae-Duk Kim.

Abstract

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.

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