Shim, Man Kyu Park, Jooho Yoon, Hong Yeol Lee, Sangmin Um, Wooram Kim, Jong-Ho Kang, Sun-Woong Seo, Joung-Wook Hyun, Soo-Wang Park, Jae Hyung Byun, Youngro Kwon, Ick Chan Kim, Kwangmeyung 2024-01-19T21:01:49Z 2024-01-19T21:01:49Z 2021-09-02 2019-01-28 0168-3659 https://pubs.kist.re.kr/handle/201004/120448 Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition. The carrier-free nanoparticles of FRRG-DOX induced cytotoxicity against cathepsin B-overexpressed tumor cells whereas the toxicity was minimized in normal cells. In particular, the FRRG-DOX nanoparticles showed the successful tumor-targeting ability and enhanced therapeutic efficiency in human colon adenocarcinoma (HT-29) tumor-bearing mice via enhanced permeation and retention (EPR) effect. Furthermore, FRRG-DOX nanoparticles did not present any severe toxicity, such as non-specific cell death and cardiac toxicity, in normal tissues due to minimal expression of cathepsin B. This carrier-free nanoparticles of FRRG-DOX can solve the unavoidable problems of current nanomedicine, such as lower targeting efficiency, toxicity of nanoparticles themselves, and difficulty in mass production that are fatally caused by natural and synthetic nano-sized carriers. English ELSEVIER SCIENCE BV DRUG-DELIVERY NANOMEDICINE EXPRESSION TOXICITY RELEASE SYSTEMS DESIGN IMPACT SIZE Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy Article 10.1016/j.jconrel.2018.11.032 1 JOURNAL OF CONTROLLED RELEASE, v.294, pp.376 - 389 JOURNAL OF CONTROLLED RELEASE 294 376 389 scie scopus 000455852000030 2-s2.0-85059456528 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article DRUG-DELIVERY NANOMEDICINE EXPRESSION TOXICITY RELEASE SYSTEMS DESIGN IMPACT SIZE Tumor targeting therapy Nanomedicine Carrier-free nanoparticles Cathepsin B-specfic prodrug