Nanoformulation of the Photoactive Cisplatin Prodrug for Combined Photothermal Therapy and Bioimaging

Cancer phototheranostics is a new mode of precise treatment based on fluorescent and photothermal imaging (PTI), combined with photodynamic (PDT) and photothermal therapy (PTT). Herein, we designed a photoactive Pt(IV) prodrug Pt-1 with BODIPY-based triplet photosensitizer as an axial ligand that exhibits cytotoxic effects through both PDT and photoactivated chemotherapy (PACT). Based on the Pt-1 prodrug, we developed a multifunctional theranostic nanoplatform Pt-NPs with combined PDT/PTT activity, capable of light-induced cisplatin release and suitable for photothermal and fluorescent tumor imaging. Upon 660 nm laser irradiation, Pt-NPs efficiently causes regional hyperpyrexia, with a photothermal conversion efficiency of 42.1%. Synergistically, Pt-NPs acts as a PDT type I agent. In vivo PTI studies have shown bright fluorescence of the CT-26 tumor after intravenous injection of Pt-NPs, indicating accumulation and retention of Pt-NPs in the tumor. This is the first example of PTT/PDT-active NPs based on Pt(IV) prodrug capable of photoinduced release of cisplatin. This strategy of the synergistic light-induced PDT/PTT/PACT action of Pt-NPs provides a new platform for the future design of phototheranostic agents for enhanced tumor treatment and imaging. © 2024 American Chemical Society.

Authors
Spector D.V. , Bykusov V. , Zharova A. , Kuzmichev I. , Isaeva Y.A. , Khaydukov E.V. , Trifanova E. , Stepanov M. , Erofeev A.S. , Gorelkin P. , Kuanaeva R. , Nikitina V.N. , Dubenskii A. , Maksimova Y. , Skvortsov D.A. , Ipatova D. , Rodin I.A. , Vokuev M.F. , Martynov A.G. , Bunin D. , Pokrovsky V.S. , Babayeva G. , Uskova T. , Abakumov M.A. , Beloglazkina E.K. , Akasov R.A. , Krasnovskaya O.O.
Journal
ACS Applied Nano Materials
Publisher
American Chemical Society
Number of issue
22
Language
English
Pages
25603-25618
Status
Published
Link
External link
DOI
10.1021/ACSANM.4C04680
Volume
7
Year
2024
Organizations
  • 1 Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow, 119991, Russian Federation
  • 2 V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Kropotkinsky per. 23, Moscow, 119034, Russian Federation
  • 3 Enikolopov Institute of Synthetic Polymer Materials RAS, Profsoyuznaya St. 70, Moscow, 117393, Russian Federation
  • 4 Moscow Pedagogical State University (MPGU), 29/7 Malaya Pirogovskaya Str., Building 1, Moscow, 119991, Russian Federation
  • 5 Mendeleev University of Chemical Technology of Russia, Miusskaya Ploshchad, 9, Building 1, Moscow, 125047, Russian Federation
  • 6 Moscow Central Research Institute of Dentistry and Maxillofacial Surgery, 16, Timura Frunze Str., Moscow, 119991, Russian Federation
  • 7 National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow, 119049, Russian Federation
  • 8 Federal State Budgetary Scientific Institution Geological Institute, Russian Academy of Sciences, Pyzhevsky per., 7, Building 1, Moscow, 119017, Russian Federation
  • 9 Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky pr., 31, Building 4, Moscow, 119071, Russian Federation
  • 10 Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russian Federation
  • 11 Department of Biochemistry, Peoples Friendship University of Russia, RUDN University, 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
  • 12 Department of Medical Nanobiotechnology, N.I. Pirogov Russian National Research Medical University, Ostrovityanova Str., 1, 6, Moscow, 117997, Russian Federation
  • 13 I.M. Sechenov First Moscow State Medical University, Trubetskaya 8-2, Moscow, 119991, Russian Federation
Keywords
BODIPY; controlled release; J-aggregates; photodynamic therapy; photothermal therapy; platinum(IV) prodrugs
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