title: Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery.
abstract: In this work, pH/redox dual-responsive carbon dots (CDs-RGD-Pt(IV)-PEG) were fabricated for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. The system consists of fluorescent carbon dots as imaging-guided drug nanocarriers, cisplatin(IV) as prodrug, and RGD peptide as active targeting ligand, which is covered by monomethoxypolyethylene glycol (mPEG) through tumor extracellular pH (6.5-6.8) responsive benzoic-imine bond. The drug nanocarriers could be tracked by multicolor fluorescence of carbon dots. After the hydrolysis of benzoic-imine bond at the tumor extracellular pH to expose the inner targeting RGD peptide, the drug nanocarriers showed effective uptake by cancer cells through RGD-integrin αvβ3 (ligand-receptor) interaction. Upon the internalization, the loaded cisplatin(IV) prodrug was reduced to cytotoxic cisplatin in reductive cytosol of cancer cells to exhibit therapeutic effects. Confocal imaging, flow cytometry, and cell viability assays using CDs-RGD-Pt(IV)-PEG were performed to reveal the enhanced uptake and better therapeutic efficiency to cancer cells with high integrin αvβ3 expression at tumor extracellular pH than that in physiological condition. The developed CDs-RGD-Pt(IV)-PEG offers a new strategy to provide safe and effective therapeutic agents based on carbon dots for promising cancer therapy.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, 637371, Singapore.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, 637371, Singapore.
authors.forename: Xiangzhao
authors.initials: X
authors.lastname: Ai
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, 637371, Singapore.
authors.forename: Huimin
authors.initials: H
authors.lastname: Ong
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, 637371, Singapore.|School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D002945:Cisplatin; D016503:Drug Delivery Systems; D006801:Humans; D039302:Integrin alphaVbeta3; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D002244:Carbon; D002945:Cisplatin
keywords: carbon dots; dual responsiveness; enhanced cancer therapy; imaging-guided delivery; tumor targeting