title: Immobilization of ALA-Zn(II) Coordination Polymer Pro-photosensitizers on Magnetite Colloidal Supraparticles for Target Photodynamic Therapy of Bladder Cancer.
abstract: 5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn(II) coordination polymers as shells (Fe3O4@ALA-Zn(II) ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn(II) ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA-Zn(II) microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA-Zn(II) shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, P. R. China.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003102:Colloids / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D006801:Humans; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011108:Polymers / Q000737:chemistry*; D011208:Powders; D011524:Protoporphyrins / Q000378:metabolism; D013696:Temperature; D013818:Thermogravimetry; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D014961:X-Ray Diffraction; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D003102:Colloids; D017319:Photosensitizing Agents; D011108:Polymers; D011208:Powders; D011524:Protoporphyrins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D015032:Zinc; D052203:Ferrosoferric Oxide
keywords: 5-aminolevulinic acid; cancer therapy; coordination polymers; magnetism; photosensitizers; targeted drug delivery