title: Disassembly of amphiphilic small molecular prodrug with fluorescence switch induced by pH and folic acid receptors for targeted delivery and controlled release.
abstract: We develop a new type of pH-responsive amphiphilic small molecular prodrug by conjugating folic acid with anti-tumour doxorubicin via a hydrazone bond. This prodrug is featured by high and precise drug loading (55.4wt%), which can self-assemble into micellar nanoparticles in neutral environment while disassemble in the presence of tumour cells expressing folic acid receptors or the acidic tumoral endosomal environment. The prodrug nanoparticles can effectively improve anticancer efficacy due to the features of pH-triggered drug release and targeted delivery. Moreover, in vitro cell study further indicated that the resulting prodrug nanoparticles had enhanced cytotoxicity for folic-acid-positive cells (HeLa) compared to folic-acid-negative cells (MCF-7). More importantly, the induced disassembly of prodrug nanoparticles can "switch on" the inherent fluorescence of the internalized doxorubicin drug in the tumour microenvironment, which can be used for the detection of tumour cells. We believe that this strategy can pave a new way for designing small molecular drug delivery systems and facilitate tumour diagnosis and treatment simultaneously.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China. Electronic address: zgxu@swu.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Shi
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China.
authors.forename: Meili
authors.initials: M
authors.lastname: Hou
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China.
authors.forename: Yong-E
authors.initials: YE
authors.lastname: Gao
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
authors.forename: Shiying
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, PR China. Electronic address: yjkang@swu.edu.cn.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism; D005453:Fluorescence; D058973:Folate Receptors, GPI-Anchored / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D058973:Folate Receptors, GPI-Anchored; D006835:Hydrazones; D008823:Micelles; D011355:Prodrugs; D004317:Doxorubicin; D005492:Folic Acid
keywords: Cancer therapy; Controlled release; Diagnosis; Drug delivery; Small molecular prodrug