Journal Article

Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine

Chen, Haiyan, Zhao, Ming, Wang, Yaonan, Wu, Jianhui, Zhang, Xiaoyi, Zhang, Yixin, Peng, Shiqi

2020

Overview

1-(4-isopropylphenyl)-β-carboline-3-carboxylic acid (ICCA) was modified by Trp-Phe-Phe to form 1-(4-isopropylphenyl)-β-carboline-3-carbonyl-Trp-Phe-Phe (ICCA-WFF). The object of preparing ICCA-WFF was to enhance the in vivo efficacy of ICCA, to explore the possible targeting action, and to visualize the nano-feature. The advantages of ICCA-WFF over ICCA were demonstrated by a series of in vivo assays, such as anti-tumor assay, anti-arterial thrombosis assay, anti-venous thrombosis assay, P-selectin expression assay, and GPIIb/IIIa expression assay. The nano-features of ICCA-WFF were visualized by TEM, SEM and AFM images. The thrombus targeting and tumor-targeting actions were evidenced by FT-MS spectrum analysis. The minimal effective dose of ICCA-WFF slowing tumor growth and inhibiting thrombosis was 10-fold lower than that of ICCA. ICCA-WFF, but not ICCA, formed nano-particles capable of safe delivery in blood circulation. In vivo ICCA-WFF, but not ICCA, can target thrombus and tumor. In thrombus and tumor, ICCA-WFF released Trp-Phe-Phe and/or ICCA. Modifying ICCA with Trp-Phe-Phe successfully enhanced the anti-tumor activity, improved the anti-thrombotic action, formed nano-particles, targeted tumor tissue and thrombus, and provided an oligopeptide modification strategy for heterocyclic compounds.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
• Subject: Animal care / Animal welfare / Animals / anti-tumor / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Carbolines - chemistry / Carbolines - pharmacology / Catalytic Domain / Cell Line, Tumor / Drug Screening Assays, Antitumor / Embolisms / Fibrinolytic Agents - chemistry / Fibrinolytic Agents - pharmacology / Heterocyclic compounds / Humans / Hydrochloric acid / ICCA / Laboratory animals / Lung cancer / Male / Mice, Inbred ICR / modification / Molecular Docking Simulation / nano-species / Nanoparticles - chemistry / Original Research / P-Selectin - chemistry / P-Selectin - metabolism / Peptides - chemistry / Peptides - pharmacology / Platelet Glycoprotein GPIIb-IIIa Complex - metabolism / Rats, Sprague-Dawley / release / Thromboembolism / Thrombophlebitis / Thrombosis / Thrombosis - blood / Thrombosis - drug therapy / thrombus targeting / Toxicity / Trp-Phe-Phe / Tumors