Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer Journal Article
| Authors: | Yang, J.; Wang, T.; Zhao, L.; Rajasekhar, V. K.; Joshi, S.; Andreou, C.; Pal, S.; Hsu, H. T.; Zhang, H.; Cohen, I. J.; Huang, R.; Hendrickson, R. C.; Miele, M. M.; Pei, W.; Brendel, M. B.; Healey, J. H.; Chiosis, G.; Kircher, M. F. |
| Article Title: | Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer |
| Abstract: | Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent ultrasmall gold quantum clusters that are stabilized by the milk metalloprotein alpha-lactalbumin. We synthesized three types of these nanoprobes that together display fluorescence across the visible and near-infrared spectra when excited at a single wavelength through optical colour coding. In live tumour-bearing mice, the near-infrared nanoprobe generates contrast for fluorescence, X-ray computed tomography and magnetic resonance imaging, and exhibits long circulation times, low accumulation in the reticuloendothelial system, sustained tumour retention, insignificant toxicity and renal clearance. An intravenously administrated near-infrared nanoprobe with a large Stokes shift facilitated the detection and image-guided resection of breast tumours in vivo using a smartphone with modified optics. Moreover, the partially unfolded structure of alpha-lactalbumin in the nanoprobe helps with the formation of an anti-cancer lipoprotein complex with oleic acid that triggers the inhibition of the MAPK and PI3K–AKT pathways, immunogenic cell death and the recruitment of infiltrating macrophages. The biodegradability and safety profile of the nanoprobes make them suitable for the systemic detection and localized treatment of cancer. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | immunohistochemistry; signal transduction; mitogen activated protein kinase; protein kinase b; adult; cancer chemotherapy; controlled study; human cell; nonhuman; nuclear magnetic resonance imaging; magnetic resonance imaging; cell proliferation; mouse; animal tissue; cell death; cell viability; apoptosis; breast cancer; steady state; tumor volume; fluorescence; animal experiment; animal model; in vivo study; cytotoxicity; immunofluorescence; in vitro study; molecular imaging; drug synthesis; phosphatidylinositol 3 kinase; histology; drug mechanism; computerized tomography; medical imaging; tumors; western blotting; cell migration; drug clearance; contrast medium; real time polymerase chain reaction; conformational transition; cell cycle phase; mammals; tumor vascularization; surface plasmon resonance; breast carcinogenesis; b raf kinase; diseases; quantum dot; fluorescence imaging; theranostics; pharmacokinetic parameters; transmission electron microscopy; activin receptor like kinase 1; infrared radiation; gold; infrared devices; electrospray; oleic acid; hydrophobicity; computer assisted surgery; reticuloendothelial system; alpha-lactalbumin; autofluorescence; biodegradability; macropinocytosis; photoluminescence; lipoprotein; near infrared spectroscopy; tumor immunogenicity; gold nanoparticle; nanoprobes; renal clearance; human; female; article; plasma protein binding; long circulations; zeta potential; x-ray computed tomography; theranostic agents; photon correlation spectroscopy; theranostic nanomedicine; mda-mb-231 cell line; reticuloendothelial systems; alpha lactalbumin; mda-mb-468 cell line; dispersity; immunogenic cell death; localized treatment; single wavelength; visible and near infrared; protein unfolding |
| Journal Title: | Nature Biomedical Engineering |
| Volume: | 4 |
| Issue: | 7 |
| ISSN: | 2157-846X |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-07-01 |
| Start Page: | 686 |
| End Page: | 703 |
| Language: | English |
| DOI: | 10.1038/s41551-020-0584-z |
| PUBMED: | 32661307 |
| PROVIDER: | scopus |
| PMCID: | PMC8255032 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
