Silica-based nanoarchitecture for an optimal combination of photothermal and chemodynamic therapy functions of Cu_2–xS cores with red emitting carbon dots

Abstract

This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities, in addition to luminescence. The activity of the silica nanoparticles is derived from their plasmonic properties, which are a result of infusing the silica nanoparticles with multiple Cu_2–xS cores. This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant. The key factors that enable the internal incorporation of the Cu_2–xS cores and the external deposition of red-emitting carbon dots are identified. The Cu_2–xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy, which are essential for photothermal and chemodynamic activities. The silica nanoparticles’ small size (no more than 70 nm) and high colloidal stability are prerequisites for their cell internalization. The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques. The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity, and the mechanisms of cell death are evaluated using an apoptotic assay. The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared (1064 nm) irradiation.

Graphical abstract

Keywords

copper sulfide nanoparticles / chemodynamic therapy / photothermal therapy / carbon dots / silica nanoparticles

References

[1] Kim M, Lee J H. Plasmonic photothermal nanoparticles for niomedical applications. Advancement of Science, 2019, 6: 1900471

[2] Nikam A N, Pandey A, Fernandes G, Kulkarni S, Mutalik S P, Padya B S, George S D, Mutalik S. Copper sulphide based heterogeneous nanoplatforms for multimodal therapy and imaging of cancer: recent advances and toxicological perspectives. Coordination Chemistry Reviews, 2020, 419: 213356

[3] Sun H, Zhang Y, Chen S, Wang R, Chen Q, Li J, Luo Y, Wang X, Chen H. Photothermal Fenton nanocatalysts for synergetic cancer therapy in the second near-infrared window. ACS Applied Materials & Interfaces, 2020, 12(27): 30145–30154

[4] Goel S, Chen F, Cai W. Synthesis and biomedical applications of copper sulfide nanoparticles: from sensors to theranostics. Small, 2014, 10(4): 631–645

[5] Tian Q, Jiang F, Zou R, Liu Q, Chen Z, Zhu M, Yang S, Wang J, Wang J, Hu J. Hydrophilic Cu₉S₅ nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. ACS Nano, 2011, 5(12): 9761–9771

[6] Marin R, Skripka A, Besteiro L V, Benayas A, Wang Z, Govorov A O, Canton P, Vetrone F. Highly efficient copper sulfide-based near-infrared photothermal agents: exploring the limits of macroscopic heat conversion. Small, 2018, 14(49): 1803282

[7] Li Y, Lu W, Huang Q, Li C, Chen W. Copper sulfide nanoparticles for photothermal ablation of tumor cells. Nanomedicine, 2010, 5(8): 1161–1171

[8] Yan C, Tian Q, Yang S. Recent advances in the rational design of copper chalcogenide to enhance the photothermal conversion efficiency for the photothermal ablation of cancer cells. RSC Advances, 2017, 7(60): 37887–37897

[9] Li S L, Chu X, Dong H L, Hou H Y, Liu Y. Recent advances in augmenting Fenton chemistry of nanoplatforms for enhanced chemodynamic therapy. Coordination Chemistry Reviews, 2023, 479: 215004

[10] Behzadi S, Serpooshan V, Tao W, Hamaly M A, Alkawareek M Y, Dreaden E C, Brown D, Alkilany A M, Farokhzad O C, Mahmoudi M. Cellular uptake of nanoparticles: journey inside the cell. Chemical Society Reviews, 2017, 46(14): 4218–4244

[11] Xu M, Yang G, Bi H, Xu J, Dong S, Jia T, Wang Z, Zhao R, Sun Q, Gai S. . An intelligent nanoplatform for imaging-guided photodynamic/photothermal/chemo-therapy based on upconversion nanoparticles and CuS integrated black phosphorus. Chemical Engineering Journal, 2020, 382: 122822

[12] Wang J, Shah Z H, Zhang S, Lu R. Silica-based nanocomposites via reverse microemulsions: classifications, preparations, and applications. Nanoscale, 2014, 6(9): 4418–4437

[13] Wei W, Wei M, Liu S. Silica nanoparticles as a carrier for signal amplification. Reviews in Analytical Chemistry, 2012, 31(3–4): 163–176

[14] Yu M, Zhao Z. Plasmon-enhanced up-conversion luminescence and oxygen vacancy defect-induced yellow light in annealed Cu₈S₅@SiO₂@Er₂O₃ nanocomposites. Journal of Luminescence, 2020, 225: 117361

[15] Yu M, Tang P, Zhang Q, Zhao Z, Huang S. Plasmon-enhanced up-conversion luminescence in multiple Cu_2–xS@SiO₂-embedded Er(OH)CO₃ composites. Journal of Alloys and Compounds, 2021, 853: 156906

[16] Liu K, Liu K, Liu J, Ren Q, Zhao Z, Wu X, Li D, Yuan F, Ye K, Li B. Copper chalcogenide materials as photothermal agents for cancer treatment. Nanoscale, 2020, 12(5): 2902–2913

[17] Wang L, Ma X, Cai K, Li X. Morphological effect of copper sulfide nanoparticles on their near infrared laser activated photothermal and photodynamic performance. Materials Research Express, 2019, 6(10): 105406

[18] Mutalik C, Okoro G, Krisnawati D I, Jazidie A, Rahmawati E Q, Rahayu D, Hsu W T, Kuo T R. Copper sulfide with morphology-dependent photodynamic and photothermal antibacterial activities. Journal of Colloid and Interface Science, 2022, 607: 1825–1835

[19] Dimitriev O, Slominskii Y, Giancaspro M, Rizzi F, Depalo N, Fanizza E, Yoshida T. Giancaspro, Rizzi F, Depalo N, Fanizza E, Yoshida T. Assembling near-infrared dye on the surface of near-infrared silica-coated copper sulphide plasmonic nanoparticles. Nanomaterials, 2023, 13(3): 510

[20] Fanizza E, Mastrogiacomo R, Pugliese O, Guglielmelli A, Sio L D, Castaldo R, Scavo M P, Giancaspro M, Rizzi F, Gentile G. . NIR-absorbing mesoporous silica-coated copper sulphide nanostructures for light-to-thermal energy conversion. Nanomaterials, 2022, 12(15): 2545

[21] Luo B, Huang X, Ye Y, Cai J, Feng Y, Cai X, Wang X. CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy. Journal of Inorganic Chemistry, 2022, 235: 111940

[22] Wang Y, An L, Lin J, Tian Q, Yang S. A hollow Cu₉S₈ theranostic nanoplatform based on a combination of increased active sites and photothermal performance in enhanced chemodynamic therapy. Chemical Engineering Journal, 2020, 385: 123925

[23] Fedorenko S, Stepanov A, Bochkova O, Kholin K, Dovjenko A, Zairov R, Nizameev I, Gerasimova T, Strelnik I, Voloshina A. . Tailoring of silica nanoarchitecture to optimize Cu_2–xS based image-guided chemodynamic therapy agent. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021, 626: 126996

[24] Fedorenko S, Farvaeva D, Stepanov A, Bochkova O, Kholin K, Nizameev I, Drobyshev S, Gerasimova T, Voloshina A, Fanizza E. . Tricks for organic-capped Cu_2–xS nanoparticles encapsulation into silica nanocomposites co-doped with red emitting luminophore for NIR activated-photothermal/chemodynamic therapy. Journal of Photochemistry and Photobiology A Chemistry, 2022, 433: 114187

[25] Ren G, Yu L, Zhu B, Tang M, Chai F, Wang C, Su Z. Orange emissive carbon dots for colorimetric and fluorescent sensing of 2,4,6-trinitrophenol by fluorescence conversion. RSC Advances, 2018, 8(29): 16095–16102

[26] Davydov N, Mustafina A, Burilov V, Zvereva E, Katsyuba S, Vagapova L, Konovalov A, Antipin I. Complex formation of d-metal ions at the interface of Tb^III -doped silica nanoparticles as a basis of substrate-responsive Tb^III-centered luminescence. ChemPhysChem, 2012, 13(14): 3357–3364

[27] Donahue N D, Acar H, Wilhelm S. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Advanced Drug Delivery Reviews, 2019, 143: 68–96

[28] Manzanares D, Ceña V. Endocytosis: the nanoparticle and submicron nanocompounds gateway into the cell. Pharmaceutics, 2020, 12(4): 371

[29] Augustine R, Hasan A, Primavera R, Wilson R J, Thakor A S, Kevadiya B D. Cellular uptake and retention of nanoparticles: insights on particle properties and interaction with cellular components. Materials Today. Communications, 2020, 25: 101692

[30] Fedorenko S V, Mustafina A R, Mukhametshina A R, Jilkin M E, Mukhametzyanov T A, Solovieva A O, Pozmogova T N, Shestopalova L V, Shestopalov M A, Kholin K V. . Cellular imaging by green luminescence of Tb(III)-doped aminomodified silica nanoparticles. Materials Science and Engineering A, 2017, 76: 551–558

[31] Elistratova J, Mukhametshina A, Kholin K, Nizameev I, Mikhailov M, Sokolov M, Khairullin R, Miftakhova R, Shammas G, Kadirov M. . Interfacial uploading of luminescent hexamolybdenum cluster units onto amino-decorated silica nanoparticles as new design of nanomaterial for cellular imaging and photodynamic therapy. Journal of Colloid and Interface Science, 2019, 538: 387–396

[32] de la Torre C, Gavara R, Garcia-Fernandez A, Mikhaylov M, Sokolov M N, Miravet J F, Sancenon F, Martinez-Manez R, Galindo F. Enhancement of photoactivity and cellular uptake of (Bu₄N)₂[Mo₆I₈(CH₃COO)₆] complex by loading on porous MCM-41 support. Photodynamic studies as an anticancer agent. Biomaterials Advances, 2022, 140: 213057

[33] Zhang Z, Zhu H, Peng N, Song J, Sun R, Wang J, Zhu F, Wang Y. Red emissive carbon dots-based probe for rapid identification and continuous tracking of Gram-positive bacteria in tumor cells. Materials Letters, 2023, 341: 134233

[34] Wang X, Cao Y, Hu X, Cai L, Wang H, Fang G, Wang S. A novel fluorescent biomimetic sensor based on cerium, nitrogen co-doped carbon quantum dots embedded in cobalt-based metal organic framework@molecularly imprinted polymer for selective and sensitive detection of oxytetracycline. Microchemical Journal, 2023, 190: 108606

[35] Luo F, Zhu M, Liu Y, Sun J, Gao F. Ratiometric and visual determination of copper ions with fluorescent nanohybrids of semiconducting polymer nanoparticles and carbon dots. Spectrochimica Acta. Part A: Molecular and Biomolecular Spectroscopy, 2023, 295: 122574

[36] Wang Y, Wu R, Zhang Y, Cheng S, Zhang Y. High quantum yield nitrogen doped carbon dots for Ag⁺ sensing and bioimaging. Journal of Molecular Structure, 2023, 1283: 135212

[37] Sajwan R K, Solanki P R. Gold@carbon quantum dots nanocomposites based two-in-one sensor: a novel approach for sensitive detection of aminoglycosides antibiotics in food samples. Food Chemistry, 2023, 415: 135590

[38] Bochkova O, Dovjenko A, Zairov R, Kholin K, Biktimirova R, Fedorenko S, Nizameev I, Laskin A, Voloshina A, Lyubina A. . Silica-supported assemblage of Cu^II ions with carbon dots for self-boosting and glutathione-induced ROS generation. Coatings, 2022, 12(1): 97

[39] Yu Y, Song M, Chen C, Du Y, Li C, Han Y, Yan F, Shi Z, Feng S. Bortezomib-encapsulated CuS/carbon dot nanocomposites for enhanced photothermal therapy via stabilization of polyubiquitinated substrates in the proteasomal degradation pathway. ACS Nano, 2020, 14(8): 10688–10703

[40] Roper D K, Ahn W, Hoepfner M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. Journal of Physical Chemistry C, 2007, 111(9): 3636–3641

[41] Ain N, Abdul Nasir J, Khan Z, Butler I S, Rehman Z. Copper sulfide nanostructures: synthesis and biological applications. RSC Advances, 2022, 12(12): 7550–7567

[42] Zhang L, Pan H, Li Y, Li F, Huang X. Constructing Cu₇S₄@SiO₂/DOX multifunctional nanoplatforms for synergistic photothermal-chemotherapy on melanoma tumors. Frontiers in Bioengineering and Biotechnology Sec. Biomaterials, 2020, 8: 579439

[43] An N, Wang Y, Li M, Lin H, Qu F. The synthesis of core-shell Cu₉S₅@mSiO₂-ICG@PEG-LA for photothermal and photodynamic therapy. New Journal of Chemistry, 2018, 42(22): 18318–18327

[44] Tang Z, Liu Y, He M, Bu W. Chemodynamic therapy: tumour microenvironment mediated Fenton and Fenton-like reactions. Angewandte Chemie International Edition, 2019, 58(4): 946–956

[45] Gao F, Liu J, Gong P, Yang Y, Jiang Y. Carbon dots as potential antioxidants for the scavenging of multi-reactive oxygen and nitrogen species. Chemical Engineering Journal, 2023, 462: 142338

[46] Zhang K, Meng X, Yang Z, Dong H, Zhang X. Enhanced cancer therapy by hypoxia-responsive copper metal-organic frameworks nanosystem. Biomaterials, 2020, 258: 120278

[47] Komarnicka U K, Pucelik B, Wojtala D, Lesiów M K, Stochel G, Kyzioł A. Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate. Scientific Reports, 2021, 11(1): 23943

[48] Tsvetkov T, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler Ryan D, Eaton J K, Frenkel E, Kocak M, Corsello S M, Lutsenko S, Kanarek N, Santagata S, Golub T R. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 2022, 375(6586): 1254–1261

[49] McBride H M, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Current Biology, 2006, 16(14): R551–R560

Competing interests

The authors declare that they have no competing interests.

Acknowledgments

The reported study was funded by RFBR and CNR, project number 20-53-7802. Authors gratefully acknowledge to Assigned Spectral-Analytical Center of FRC Kazan Scientific Center of RAS for providing necessary facilities to carry out physical-chemical measurements. The authors thanks to Interdisciplinary Center for Analytical Microscopy at KFU for assistance with the confocal microscopy experiments.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11705-023-2362-4 and is accessible for authorized users.

RIGHTS & PERMISSIONS

2023 Higher Education Press