title: pH-responsive metallo-supramolecular nanogel for synergistic chemo-photodynamic therapy.
abstract: Benefited from the high orientation of coordinated interaction, metallo-supramolecular materials have attracted enormous interest in many fields. Herein, a novel metallo-supramolecular nanogel (SNG)-based drug delivery system for synergistic chemo-photodynamic therapy is explored to enhance anticancer efficacy. It is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. It can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells. Zn-Por moieties in SNG keep the photosensitivity in the range of visible wavelength and possess the ability of generating active oxygen species for photodynamic therapy. The drug-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy. Compared with the single chemotherapy of free doxorubicine (DOX) or photodynamic therapy of Zn-Por in SNG, DOX-loaded SNG with irradiation shows higher in vitro cytotoxicity and in vivo anticancer therapeutic activity, endowing the SNG with great potential in cancer treatments.
  A combination of multiple non-cross-resistant anticancer agents has been widely applied clinically. Applying multiple drugs with different molecular targets can raise the genetic barriers and delay the cancer adaption process. Multiple drugs targeting different cellular pathways can function synergistically, giving higher therapeutic efficacy and target selectivity. Overall, developing a combination therapeutic approach might even be the key to enhance anticancer efficacy and overcome chemo-resistance. Herein, a novel metallo-supramolecular nanogel (SNG) is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. The DOX-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy because it can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells.
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China. Electronic address: chenl686@nenu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D000080385:Nanogels; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D008670:Metals; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Chemo-photodynamic therapy; Metallo-supramolecular nanogel; Synergistic treatment; pH-responsiveness