A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboida...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 116; no. 41; pp. 20296 - 20302
Main Authors Zhou, Zhixuan, Liu, Jiangping, Huang, Juanjuan, Rees, Thomas W., Wang, Yiliang, Wang, Heng, Li, Xiaopeng, Chao, Hui, Stang, Peter J.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 08.10.2019
Subjects
A549 Cells
Absorption cross sections
Animals
Biological properties
Block copolymers
Cytotoxicity
Drug Development
Humans
I.R. radiation
In vivo methods and tests
Infrared radiation
Internalization
Irradiation
Light irradiation
Localization
Lysosomes
Metal Nanoparticles
Mice
Nanoparticles
Neoplasms, Experimental - drug therapy
Organometallic compounds
Photochemotherapy - methods
Photodynamic therapy
Photon absorption
Photons
Photosensitizing Agents - chemistry
Photosensitizing Agents - pharmacology
Physical Sciences
Platinum Compounds
Reactive oxygen species
Ruthenium
Ruthenium Compounds
Self-assembly
Spheroids
Tumor cells
Tumors
self-assembly
lysosome
photodynamic therapy
2-photon absorption
coordination
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Summary:Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.
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Contributed by Peter J. Stang, August 26, 2019 (sent for review July 22, 2019; reviewed by Kendall N. Houk and Timothy M. Swager)
Author contributions: Z.Z., J.L., H.C., and P.J.S. designed research; Z.Z. and J.L. performed research; H.W. and X.L. contributed new reagents/analytic tools; Z.Z., J.L., J.H., T.W.R., Y.W., H.C., and P.J.S. analyzed data; and Z.Z., J.L., J.H., T.W.R., H.C., and P.J.S. wrote the paper.
1Z.Z. and J.L. contributed equally to this work.
Reviewers: K.N.H., University of California, Los Angeles; and T.M.S., Massachusetts Institute of Technology.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1912549116