title: Bioengineered yeast-derived vacuoles with enhanced tissue-penetrating ability for targeted cancer therapy.
abstract: Despite the appreciable success of synthetic nanomaterials for targeted cancer therapy in preclinical studies, technical challenges involving their large-scale, cost-effective production and intrinsic toxicity associated with the materials, as well as their inability to penetrate tumor tissues deeply, limit their clinical translation. Here, we describe biologically derived nanocarriers developed from a bioengineered yeast strain that may overcome such impediments. The budding yeast Saccharomyces cerevisiae was genetically engineered to produce nanosized vacuoles displaying human epidermal growth factor receptor 2 (HER2)-specific affibody for active targeting. These nanosized vacuoles efficiently loaded the anticancer drug doxorubicin (Dox) and were effectively endocytosed by cultured cancer cells. Their cancer-targeting ability, along with their unique endomembrane compositions, significantly enhanced drug penetration in multicellular cultures and improved drug distribution in a tumor xenograft. Furthermore, Dox-loaded vacuoles successfully prevented tumor growth without eliciting any prolonged immune responses. The current study provides a platform technology for generating cancer-specific, tissue-penetrating, safe, and scalable biological nanoparticles for targeted cancer therapy.
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Vipul
authors.initials: V
authors.lastname: Gujrati
authors.affiliation: School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
authors.forename: Sangeun
authors.initials: S
authors.lastname: Lee
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Kim
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Sukmo
authors.initials: S
authors.lastname: Kang
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Jinjoo
authors.initials: J
authors.lastname: Kim
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Hyungsu
authors.initials: H
authors.lastname: Jeon
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea;
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea junys@gist.ac.kr syjon@kaist.ac.kr.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
authors.affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; junys@gist.ac.kr syjon@kaist.ac.kr.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D057005:Bioengineering; D016923:Cell Death / Q000187:drug effects; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D009928:Organ Specificity; D000067996:RAW 264.7 Cells; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects; D014617:Vacuoles / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: affibody; bioengineered yeast; cancer therapy; drug delivery; yeast vacuoles