title: Promotion of initial anti-tumor effect via polydopamine modified doxorubicin-loaded electrospun fibrous membranes.
abstract: Drug-loaded electrospun PLLA membranes are not conducive to adhesion between materials and tissues due to the strong hydrophobicity of PLLA, which possibly attenuate the drugs' effect loaded on the materials. In the present work, we developed a facile method to improve the hydrophilicity of doxorubicin (DOX)-loaded electrospun PLLA fibrous membranes, which could enhance the anti-tumor effect at the early stage after implantation. A mussel protein, polydopamine (PDA), could be easily grafted on the surface of hydrophobic DOX-loaded electrospun PLLA membranes (PLLA-DOX/pDA) in water solution. The morphology analysis of PLLA-DOX/pDA fibers displayed that though the fiber diameter was slightly swollen, they still maintained a 3D fibrous structure, and the XPS analysis certified that pDA had successfully been grafted onto the surface of the fibers. The results of surface wettability analysis showed that the contact angle decreased from 136.7° to 0° after grafting. In vitro MTT assay showed that the cytotoxicity of PLLA-DOX/pDA fibers was the strongest, and the stereologic cell counting assay demonstrated that the adhesiveness of PLLA/pDA fiber was significantly better than PLLA fiber. In vivo tumor-bearing mice displayed that, after one week of implantation, the tumor apoptosis and necrosis of PLLA-DOX/pDA fibers were the most obvious from histopathology and TUNEL assay. The caspase-3 activity of PLLA-DOX/pDA group was the highest using biochemical techniques, and the Bax: Bcl-2 ratio increased significantly in PLLA-DOX/pDA group through qRT-PCR analysis. All the results demonstrated that pDA can improve the affinity of the electrospun PLLA membranes and enhance the drug effect on tumors.
authors.affiliation: Department of General Surgery, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University 600 Yishan Road, Shanghai 200233, P. R. China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Orthopedic Institute, Soochow University 708 Renmin Road, Suzhou 215006, Jiangsu, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University 600 Yishan Road, Shanghai 200233, P. R. China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University 600 Yishan Road, Shanghai 200233, P. R. China.
authors.forename: Wangwang
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Orthopedic Institute, Soochow University 708 Renmin Road, Suzhou 215006, Jiangsu, P. R. China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University 600 Yishan Road, Shanghai 200233, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Orthopedic Institute, Soochow University 708 Renmin Road, Suzhou 215006, Jiangsu, P. R. China ; Department of Orthopedics, The First Affiliated Hospital of Soochow University 188 Shizi Street, Suzhou 215006, Jiangsu, P. R. China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008567:Membranes, Artificial; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008968:Molecular Conformation; D009336:Necrosis; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013499:Surface Properties; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D004337:Drug Carriers; D004343:Drug Implants; D007211:Indoles; D008567:Membranes, Artificial; D011091:Polyesters; D011108:Polymers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C568283:polydopamine; D019344:Lactic Acid; C033616:poly(lactide); D004317:Doxorubicin; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Cancer; PLLA; electrospun; hydrophobicity; polydopamine