Phosphorescent Metal Halide Nanoclusters for Tunable Photodynamic Therapy

Overview

Journal Chemistry

Specialty Chemistry

Date 2022 Nov 9

PMID 36351205

Authors

Hyllana C D Medeiros

Chenchen Yang

Christopher K Herrera

Deanna Broadwater

Elliot Ensink

Matthew Bates

Richard R Lunt

Sophia Y Lunt

Affiliations

Soon will be listed here.

Abstract

Photodynamic therapy (PDT) is currently limited by the inability of photosensitizers (PSs) to enter cancer cells and generate sufficient reactive oxygen species. Utilizing phosphorescent triplet states of novel PSs to generate singlet oxygen offers exciting possibilities for PDT. Here, we report phosphorescent octahedral molybdenum (Mo)-based nanoclusters (NC) with tunable toxicity for PDT of cancer cells without use of rare or toxic elements. Upon irradiation with blue light, these molecules are excited to their singlet state and then undergo intersystem crossing to their triplet state. These NCs display surprising tunability between their cellular cytotoxicity and phototoxicity by modulating the apical halide ligand with a series of short chain fatty acids from trifluoroacetate to heptafluorobutyrate. The NCs are effective in PDT against breast, skin, pancreas, and colon cancer cells as well as their highly metastatic derivatives, demonstrating the robustness of these NCs in treating a wide variety of aggressive cancer cells. Furthermore, these NCs are internalized by cancer cells, remain in the lysosome, and can be modulated by the apical ligand to produce singlet oxygen. Thus, (Mo)-based nanoclusters are an excellent platform for optimizing PSs. Our results highlight the profound impact of molecular nanocluster chemistry in PDT applications.

Citing Articles

Phosphorescent Metal Halide Nanoclusters for Tunable Photodynamic Therapy.

Medeiros H, Yang C, Herrera C, Broadwater D, Ensink E, Bates M Chemistry. 2022; 29(7):e202202881.

PMID: 36351205 PMC: 9898232. DOI: 10.1002/chem.202202881.

References

Gonzalez-Reymundez A, de Los Campos G, Gutierrez L, Lunt S, Vazquez A . Prediction of years of life after diagnosis of breast cancer using omics and omic-by-treatment interactions. Eur J Hum Genet. 2017; 25(5):538-544. PMC: 5437894. DOI: 10.1038/ejhg.2017.12. View

P Ogrodzinski M, Teoh S, Lunt S . Targeting Subtype-Specific Metabolic Preferences in Nucleotide Biosynthesis Inhibits Tumor Growth in a Breast Cancer Model. Cancer Res. 2020; 81(2):303-314. DOI: 10.1158/0008-5472.CAN-20-1666. View

Shen W, Hu T, Liu X, Zha J, Meng F, Wu Z . Defect engineering of layered double hydroxide nanosheets as inorganic photosensitizers for NIR-III photodynamic cancer therapy. Nat Commun. 2022; 13(1):3384. PMC: 9192653. DOI: 10.1038/s41467-022-31106-9. View

P Ogrodzinski M, Teoh S, Lunt S . Metabolomic profiling of mouse mammary tumor-derived cell lines reveals targeted therapy options for cancer subtypes. Cell Oncol (Dordr). 2020; 43(6):1117-1127. DOI: 10.1007/s13402-020-00545-1. View

Iulianna T, Kuldeep N, Eric F . The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death. Cell Death Dis. 2022; 13(5):509. PMC: 9151667. DOI: 10.1038/s41419-022-04912-8. View

Zhang C, Chen W, Zhang T, Jiang X, Hu Y . Hybrid nanoparticle composites applied to photodynamic therapy: strategies and applications. J Mater Chem B. 2020; 8(22):4726-4737. DOI: 10.1039/d0tb00093k. View

Elistratova J, Mukhametshina A, Kholin K, Nizameev I, Mikhailov M, Sokolov M . Interfacial uploading of luminescent hexamolybdenum cluster units onto amino-decorated silica nanoparticles as new design of nanomaterial for cellular imaging and photodynamic therapy. J Colloid Interface Sci. 2018; 538:387-396. DOI: 10.1016/j.jcis.2018.12.013. View

Rinaldi G, Pranzini E, Van Elsen J, Broekaert D, Funk C, Planque M . In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition. Mol Cell. 2020; 81(2):386-397.e7. PMC: 9161668. DOI: 10.1016/j.molcel.2020.11.027. View

Hou Y, Fu Q, Kuang Y, Li D, Sun Y, Qian Z . Unsaturated fatty acid-tuned assembly of photosensitizers for enhanced photodynamic therapy via lipid peroxidation. J Control Release. 2021; 334:213-223. DOI: 10.1016/j.jconrel.2021.04.022. View

10.

Brandhonneur N, Boucaud Y, Verger A, Dumait N, Molard Y, Cordier S . Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer. Int J Pharm. 2020; 592:120079. DOI: 10.1016/j.ijpharm.2020.120079. View

11.

Kuttipillai P, Zhao Y, Traverse C, Staples R, Levine B, Lunt R . Phosphorescent Nanocluster Light-Emitting Diodes. Adv Mater. 2015; 28(2):320-6. DOI: 10.1002/adma.201504548. View

12.

Brandhonneur N, Hatahet T, Amela-Cortes M, Molard Y, Cordier S, Dollo G . Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer. Eur J Pharm Biopharm. 2018; 125:95-105. DOI: 10.1016/j.ejpb.2018.01.007. View

13.

Svezhentseva E, Vorotnikov Y, Solovieva A, Pozmogova T, Eltsov I, Ivanov A . From Photoinduced to Dark Cytotoxicity through an Octahedral Cluster Hydrolysis. Chemistry. 2018; 24(68):17915-17920. DOI: 10.1002/chem.201804663. View

14.

Goodarzi H, Zhang S, Buss C, Fish L, Tavazoie S, Tavazoie S . Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins. Nature. 2014; 513(7517):256-60. PMC: 4440807. DOI: 10.1038/nature13466. View

15.

Qi S, Guo L, Yan S, Lee R, Yu S, Chen S . Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway. Acta Pharm Sin B. 2019; 9(2):279-293. PMC: 6437636. DOI: 10.1016/j.apsb.2018.12.004. View

16.

Simelane N, Kruger C, Abrahamse H . Photodynamic diagnosis and photodynamic therapy of colorectal cancer and . RSC Adv. 2022; 10(68):41560-41576. PMC: 9058000. DOI: 10.1039/d0ra08617g. View

17.

Radu A, Conde R, Fontolliet C, Wagnieres G, van den Bergh H, Monnier P . Mucosal ablation with photodynamic therapy in the esophagus: optimization of light dosimetry in the sheep model. Gastrointest Endosc. 2003; 57(7):897-905. DOI: 10.1016/s0016-5107(03)70027-3. View

18.

Xu G, Li C, Chi C, Wu L, Sun Y, Zhao J . A supramolecular photosensitizer derived from an Arene-Ru(II) complex self-assembly for NIR activated photodynamic and photothermal therapy. Nat Commun. 2022; 13(1):3064. PMC: 9163081. DOI: 10.1038/s41467-022-30721-w. View

19.

Broadwater D, Bates M, Jayaram M, Young M, He J, Raithel A . Modulating cellular cytotoxicity and phototoxicity of fluorescent organic salts through counterion pairing. Sci Rep. 2019; 9(1):15288. PMC: 6814864. DOI: 10.1038/s41598-019-51593-z. View

20.

Zhou Z, Liu J, Huang J, Rees T, Wang Y, Wang H . A self-assembled Ru-Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy. Proc Natl Acad Sci U S A. 2019; 116(41):20296-20302. PMC: 6789806. DOI: 10.1073/pnas.1912549116. View