Vipul Gujratia, Miriam Leeb, Young-Joon Kob, Sangeun Leeb, Daejin Kima, Hyungjun Kima, Sukmo Kanga, Soyoung Leea, Jinjoo Kima, Hyungsu Jeona, Sun Chang Kima, Youngsoo Junb,1, and Sangyong Jona,1
aKAIST 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;
bSchool of Life Sciences and Silver Health Bio Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
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.
affibody, bioengineered yeast, cancer therapy, drug delivery, yeast vacuoles
1To whom correspondence may be addressed.
Author contributions: V.G. and S.J. designed research; V.G., M.L., Y.-J.K., Sangeun Lee, D.K., H.K., S.K., Soyoung Lee, J.K., and H.J. performed research; S.J. contributed new reagents/analytic tools; V.G., S.C.K., Y.J., and S.J. analyzed data; V.G., Y.J., and S.J. wrote the paper; M.L., Y.-J.K., and Y.J. provided vacuoles; and S.J. conceived the project.