  Citation: Jarockyte, G.; Poderys, V.; Barzda, V.; Karabanovas, V.; Rotomskis, R. Blood Plasma Stabilized Gold Nanoclusters for Personalized Tumor Theranostics. Cancers 2022, 14, 1887. https:// doi.org/10.3390/cancers14081887 Academic Editor: Giacomo Reina Received: 11 March 2022 Accepted: 6 April 2022 Published: 8 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article Blood Plasma Stabilized Gold Nanoclusters for Personalized Tumor Theranostics Greta Jarockyte 1,2,3 , Vilius Poderys 1 , Virginijus Barzda 3,4,5 , Vitalijus Karabanovas 1,6, * and Ricardas Rotomskis 1,3 1 Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania; greta.jarockyte@nvi.lt (G.J.); vilius.poderys@nvi.lt (V.P.); ricardas.rotomskis@nvi.lt (R.R.) 2 Life Science Center, Vilnius University, LT-10257 Vilnius, Lithuania 3 Laser Research Center, Faculty of Physics, Vilnius University, LT-10223 Vilnius, Lithuania; virgis.barzda@utoronto.ca 4 Department of Chemical and Physical Sciences, University of Toronto Mississauga, Toronto, ON L5L 1C6, Canada 5 Department of Physics, University of Toronto, Toronto, ON M5S 1A7, Canada 6 Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania * Correspondence: vitalijus.karabanovas@nvi.lt Simple Summary: Cancer is a disease that has a high fatality rate over the world. Nanotechnology is one of the most promising current approaches for developing novel diagnostic and treatment methods in accomplishing more personalized medicine. Personalized gold nanoclusters have potential to be used in cancer theranostics. We demonstrate that biocompatible gold nanoclusters could be synthesized directly in human blood plasma. Such gold nanoclusters have a wide photoluminescence band in the optical tissue window and generate reactive oxygen species under irradiation with visible light, thus are suitable for cancer theranostics. Abstract: Personalized cancer theranostics has a potential to increase efficiency of early cancer diag- nostics and treatment, and to reduce negative side-effects. Protein-stabilized gold nanoclusters may serve as theranostic agents. To make gold nanoclusters personalized and highly biocompatible, the clusters were stabilized with human plasma proteins. Optical properties of synthesized nanoclusters were investigated spectroscopically, and possible biomedical application was evaluated using stan- dard cell biology methods. The spectroscopic investigations of human plasma proteins stabilized gold nanoclusters revealed that a wide photoluminescence band in the optical tissue window is suitable for cancer diagnostics. High-capacity generation of singlet oxygen and other reactive oxygen species was also observed. Furthermore, the cluster accumulation in cancer cells and the photodynamic effect were evaluated. The results demonstrate that plasma proteins stabilized gold nanoclusters that accumulate in breast cancer cells and are non-toxic in the dark, while appear phototoxic under irradiation with visible light. The results positively confirm the utility of plasma protein stabilized gold nanoclusters for the use in cancer diagnostics and treatment. Keywords: biosynthesis; nanomedicine; fluorescent diagnostic; photodynamic cancer therapy 1. Introduction Cancer remains one of the diseases with a high level of complexity that necessitates multi-step diagnostic and treatment procedures. With rapid nanotechnology development, there has been, recently, an increased use of nanomedicine in oncology. In the last decade, ample efforts were dedicated to the development of molecular and particle agents that can be used for both cancer diagnosis and treatment. The field of such research known as “theranostics”, a term used to characterize the combined therapeutic and diagnostic Cancers 2022, 14, 1887. https://doi.org/10.3390/cancers14081887 https://www.mdpi.com/journal/cancers