Kim, Jinseong Shim, Man Kyu Cho, Young-Jae Jeon, Sangmin Moon, Yujeong Choi, Jiwoong Kim, Jeongrae Lee, Jaewan Lee, Jeong-Won Kim, Kwangmeyung 2024-01-19T13:03:54Z 2024-01-19T13:03:54Z 2022-01-25 2021-12 0142-9612 https://pubs.kist.re.kr/handle/201004/115981 Intraperitoneal (IP) chemotherapy has shown promising efficacy in ovarian cancer with peritoneal carcinomatosis (PC), but in vivo rapid clearance and severe toxicity of free anticancer drugs hinder the effective treatment. Herein, we propose the safe and effective IP chemotherapy with cathepsin B-specific doxorubicin prodrug nanoparticles (PNPs) in ovarian cancer with PC. The PNPs are prepared by self-assembling cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates, which are further formulated with pluronic F68. The PNPs exhibit stable spherical structure and cytotoxic DOX is specifically released from PNPs via sequential enzymatic degradation by cathepsin B and intracellular proteases. The PNPs induce cytotoxicity in cathepsin Boverexpressing ovarian (SKOV-3 and HeyA8) and colon (MC38 and CT26) cancer cells, but not in cathepsin Bdeficient normal cells in cultured condition. With enhanced cancer-specificity and in vivo residence time, IP injected PNPs efficiently accumulate within PC through two targeting mechanisms of direct penetration (circulation independent) and systemic blood vessel-associated accumulation (circulation dependent). As a result, IP chemotherapy with PNPs efficiently inhibit tumor progression with minimal side effects in peritoneal human ovarian tumor-bearing xenograft (POX) and patient derived xenograft (PDX) models. These results demonstrate that PNPs effectively inhibit progression of ovarian cancer with peritoneal carcinomatosis with minimal local and systemic toxicities by high cancer-specificity and favorable in vivo PK/PD profiles enhancing PC accumulation. English ELSEVIER SCI LTD The safe and effective intraperitoneal chemotherapy with cathepsin B-specific doxorubicin prodrug nanoparticles in ovarian cancer with peritoneal carcinomatosis Article 10.1016/j.biomaterials.2021.121189 1 BIOMATERIALS, v.279 BIOMATERIALS 279 N scie scopus 000710899600001 2-s2.0-85117802436 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article DELIVERY PACLITAXEL THERAPY Intraperitoneal chemotherapy Peritoneal carcinomatosis Ovarian cancer Nano-sized drug delivery Cathepsin B-Specific doxorubicin prodrug nanoparticle