title: Real-time monitoring of anticancer drug release with highly fluorescent star-conjugated copolymer as a drug carrier.
abstract: Chemotherapy is one of the major systemic treatments for cancer, in which the drug release kinetics is a key factor for drug delivery. In the present work, a versatile fluorescence-based real-time monitoring system for intracellular drug release has been developed. First, two kinds of star-conjugated copolymers with different connections (e.g., pH-responsive acylhydrazone and stable ether) between a hyperbranched conjugated polymer (HCP) core and many linear poly(ethylene glycol) (PEG) arms were synthesized. Owing to the amphiphilic three-dimensional architecture, the star-conjugated copolymers could self-assemble into multimicelle aggregates from unimolecular micelles with excellent emission performance in the aqueous medium. When doxorubicin (DOX) as a model drug was encapsulated into copolymer micelles, the emission of star-conjugated copolymer and DOX was quenched. In vitro biological studies revealed that fluorescent intensities of both star-conjugated copolymer and DOX were activated when the drug was released from copolymeric micelles, resulting in the enhanced cellular proliferation inhibition against cancer cells. Importantly, pH-responsive feature of the star-conjugated copolymer with acylhydrazone linkage exhibited accelerated DOX release at a mildly acidic environment, because of the fast breakage of acylhydrazone in endosome or lysosome of tumor cells. Such fluorescent star-conjugated copolymers may open up new perspectives to real-time study of drug release kinetics of polymeric drug delivery systems for cancer therapy.
authors.affiliation: School of Chemistry and Chemical Engineering, Shanghai Key Lab of Electrical Insulation and Thermal Aging, ‡Department of Electronic Engineering, and §Instrumental Analysis Center, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Gangsheng
authors.initials: G
authors.lastname: Tong
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lu
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000032:analysis / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D004705:Endocytosis; D005453:Fluorescence; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells / Q000187:drug effects; D051379:Mice; D008823:Micelles; D015394:Molecular Structure; D041681:NIH 3T3 Cells / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006835:Hydrazones; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin