title: Preparation of Engineered Salmonella Typhimurium-Driven Hyaluronic-Acid-Based Microbeads with Both Chemotactic and Biological Targeting Towards Breast Cancer Cells for Enhanced Anticancer Therapy.
abstract: In this study, a new type of targeted bacteriobots is prepared and investigated as a therapeutic strategy against solid tumors. Maleimide-functionalized hyaluronic acid (HA) polymer is synthesized and cross-linked with four-arm-thiolated polyethylene glycol (PEG-SH) to form HA microbeads with diameter of 8 μm through the Michael-type addition. Docetaxel (DTX)-loaded nanoparticles are encapsulated in HA-PEG microbeads and sustained in vitro drug-release pattern of the DTX from the HA-PEG microbeads is observed for up to 96 h. Dual-targeted bacteriobots are prepared using CD 44 receptor-targeted HA microbeads synthesized via microfluidics, followed by the attachment of the flagellar bacterium Salmonella typhimurium, which have been genetically engineered for tumor targeting, onto the surface of the HA microbeads by the specific interaction between streptavidin on the HA beads and biotin on the bacteria. After the attachment of bacteria, the bacteriobots show an average velocity of 0.72 μm s(-1) and high chemotactic migration velocity of 0.43 μm s(-1) towards 4T1 cells lysates. CD 44 receptor-specific cellular uptake is verified through flow cytometry analysis and confocal imaging, demonstrating enhanced intracellular uptake in CD 44 receptor positive tumor cells compared to normal cells. Therefore, the present study suggests that these bacteriobots have dual-tumor-targeting abilities displaying their potential for targeted anticancer therapy.
authors.affiliation: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.
authors.forename: Saji
authors.initials: S
authors.lastname: Uthaman
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Zheng
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Cho
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Van Du
authors.initials: VD
authors.lastname: Nguyen
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Jong-Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: School of Mechanical Engineering Chonnam National University, 77 Yongbong-ro, Gwangju, 500-757, Republic of Korea.
authors.forename: Sukho
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects*; D000077143:Docetaxel; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005818:Genetic Engineering; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D008863:Microspheres; D009068:Movement; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066244:Proton Magnetic Resonance Spectroscopy; D012486:Salmonella typhimurium / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D008301:Maleimides; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid
keywords: CD 44 receptor; Salmonella typhimurium; bacteriobots; dual-tumor targeting; hyaluronic acid