Nanosized Anti-Stokes Phosphors for Antitumor Drug Delivery and Solid Tumor Theranostics
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
Nanosized Anti-Stokes Phosphors for Antitumor Drug Delivery and Solid Tumor Theranostics R. A. Akasova,b,c,*, P. A. Deminaa,c, V. V. Zasedatelevaa, N. V. Sholinab,c, D. A. Khochenkovd,e, A. N. Generalovaa,c, J. Senthil Selvanf, E. V. Khaydukovc, and Academician V. Ya. Panchenkoc Received April 10, 2020; revised April 30, 2020; accepted April 30, 2020
Abstract—Theranostics is the direction in modern biomedicine aimed at developing drugs that combine the capabilities of diagnosis and therapy of tumors in one agent. Upconversion nanophosphors (UCNPs) are inorganic crystalline materials that can be used to create a nanoplatform providing diagnostic and therapeutic modalities. They have been proposed as luminescent markers for optical imaging of biological tissue due to their anti-Stokes luminescence, lack of photodegradation and low toxicity. In this article, UCNPs as a theranostic agent for both optical imaging and delivery of anticancer drugs have been offered. To obtain biocompatible nanocomplexes, UCNP surface with a core/shell structure of NaYF4:Yb3+Tm3+/NaYF4 was modified with polylactic acid in the presence of various stabilizers (dextran, polyvinyl alcohol, and poly-N-vinylpyrrolidone). To give the therapeutic modality to the nanocomplex, the antitumor antibiotic doxorubicin was loaded into the polymer shell. The loading efficiency was up to 0.1 mg per 1 mg UCNPs. The toxicity and the intracellular accumulation of nanocomplexes were evaluated in vitro. It was concluded that the modification of UCNPs with polylactic acid provides the transport of doxorubicin, allowing the combination of diagnostic and therapeutic modalities in one agent. Keywords: upconversion nanophosphors, theranostics, doxorubicin, polylactic acid, cytotoxicity DOI: 10.1134/S1607672920050014
INTRODUCTION Currently, the development of nanosystems for tumor theranostics is one of the most rapidly developing fields in biomedicine. The most promising are multimodal systems that can be a platform for various imaging methods (e.g., for magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET)/single photon emission computed tomography (SPECT)) [1]. Such multimodal platforms include upconversion nanophosphors (UCNPs), the advantages of which as theranostic agents have been actively discussed in the last few years [2–4]. a Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia b Sechenov First Moscow State Medical University, Moscow, Russia c Federal Scientific Research Center “Crystallography and Photonics,” Russian Academy of Sciences, Moscow, Russia d Blokhin National Medical Research Center for Oncology, Ministry of Health of the Russian Federation, Moscow, Russia e Togliatti State University, Togliatti, Russia fDepartment of Nuclear Physics, University of Madras, Madras, India *e-mail: [email protected]
In this work, UCNPs loaded with anticancer drugs are proposed as agents for solid tumor theranostics. Due to
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