title: Charge-Convertible Carbon Dots for Imaging-Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency.
abstract: Carbon dots (CDs) are remarkable nanocarriers due to their promising optical and biocompatible capabilities. However, their practical applicability in cancer therapeutics is limited by their insensitive surface properties to complicated tumor microenvironment in vivo. Herein, a tumor extracellular microenvironment-responsive drug nanocarrier based on cisplatin(IV) prodrug-loaded charge-convertible CDs (CDs-Pt(IV)@PEG-(PAH/DMMA)) was developed for imaging-guided drug delivery. An anionic polymer with dimethylmaleic acid (PEG-(PAH/DMMA)) on the fabricated CDs-Pt(IV)@PEG-(PAH/DMMA) could undergo intriguing charge conversion to a cationic polymer in mildly acidic tumor extracellular microenvironment (pH ∼ 6.8), leading to strong electrostatic repulsion and release of positive CDs-Pt(IV). Importantly, positively charged nanocarrier displays high affinity to negatively charged cancer cell membrane, which results in enhanced internalization and effective activation of cisplatin(IV) prodrug in the reductive cytosol. The in vitro experimental results confirmed that this promising charge-convertible nanocarrier possesses better therapeutic efficiency under tumor extracellular microenvironment than normal physiological condition and noncharge-convertible nanocarrier. The in vivo experiments further demonstrated high tumor-inhibition efficacy and low side effects of the charge-convertible CDs, proving its capability as a smart drug nanocarrier with enhanced therapeutic effects. The present work provides a strategy to promote potential clinical application of CDs in the cancer treatment.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, Singapore 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, Singapore 637371, Singapore.
authors.forename: Xiangzhao
authors.initials: X
authors.lastname: Ai
authors.affiliation: School of Chemistry and Materials Science, Heilongjiang University , Harbin, Heilongjiang 150080, China.|College of Materials Science and Chemical Engineering, Harbin Engineering University , Harbin, Heilongjiang 150001, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: An
authors.affiliation: College of Materials Science and Chemical Engineering, Harbin Engineering University , Harbin, Heilongjiang 150001, China.
authors.forename: Piaoping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, Singapore 637371, Singapore.|School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, Singapore 639798, Singapore.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D061848:Optical Imaging; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011073:Polyamines; C063994:polyallylamine; D011092:Polyethylene Glycols; D002244:Carbon; D002945:Cisplatin
keywords: cancer therapy; carbon dots; charge convertibility; imaging guiding; in vivo studies