Light-Triggered Trafficking to the Cell Nucleus of a Cationic Polyamidoamine Functionalized with Ruthenium Complexes

Mascheroni, Luca; Francia, Valentina; Rossotti, Beatrice; Ranucci, Elisabetta; Ferruti, Paolo; Maggioni, Daniela; Salvati, Anna

doi:10.1021/acsami.0c08033

Cited by 7 publications

(4 citation statements)

References 59 publications

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“…Apoptotic cell death mechanism by the AO/EB staining assay of RuG0 , RuG1 , and RuG2 in A549, MDA MB 231, and HepG2 cells is shown in Figures , S16, and S17, respectively. As illustrated in the fluorescence microscopy images of Ru(II) coordination entity-treated cells, the AO/EB staining clearly indicates that the coordination entities have induced apoptosis in the respective cell lines, − as evident from the MTT assay. The AO/EB fluorescence microscopy images of HepG2 cell lines have shown higher apoptosis with the prepared coordination entities.…”

Section: Resultsmentioning

confidence: 83%

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities

Raju,

Javan Nikkhah,

et al. 2023

ACS Appl. Bio Mater.

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This paper studies the anticancer potency of dendritic poly(aryl ether)-substituted polypyridyl ligand-based ruthenium(II) coordination entities. The dendritic coordination entities were successfully designed, synthesized, and characterized by different spectral methods such as Fourier transform infrared (FTIR), 1H and 13C− NMR, and mass spectrometry. Further, to understand the structure and solvation behavior of the coordination entities, we performed all-atom molecular dynamics (MD) simulations. The behavior, configuration, and size of the coordination entities in DMSO and water were studied by calculating the radius of gyration (R g) and solvent-accessible surface area (SASA). The MTT assay was used to assess the in vitro cytotoxicity of all of the coordination entities against cancerous A549 (lung cancer cells), MDA MB 231 (breast cancer cells), and HepG2 (liver cancer cells) and was found to be good with comparable IC50 values with respect to the standard drug cisplatin. The coordination entities exhibited dose dependence, and the highest activity was shown against HepG2 cell lines in comparison to the other cancer cell lines. In addition, fluorescence staining studies, such as AO/EB, DAPI, and cell death analysis by PI staining, were performed on the coordination entities to understand the apoptosis mechanism. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays confirmed apoptosis in cancer cells via the mitochondrial pathway. The DNA fragmentation assay was done followed by molecular docking analysis with DNA executed to strengthen and support the experimental observations.

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Section: Resultsmentioning

confidence: 83%

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities

Raju,

Javan Nikkhah,

et al. 2023

ACS Appl. Bio Mater.

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“…Such nuclear stains are cationic in nature and highly aminated, which promotes electrostatic as well as hydrogen bonding interactions with the phosphate backbone of DNA . Similarly, previous studies have demonstrated that cationic nanoparticles preferentially target the nucleus. , To achieve this with aC′ dots, we condensed (3-(2-aminoethylamino)propyl)trimethoxysilane (AEAPTMS) onto the surface of DEAC-aC′ dots via PPSMI. Unreacted AEAPTMS was removed using GPC.…”

Section: Results and Discussionmentioning

confidence: 96%

“…43 Similarly, previous studies have demonstrated that cationic nanoparticles preferentially target the nucleus. 44,45 To achieve this with aC′ dots, we condensed (3-(2-aminoethylamino)propyl)trimethoxysilane (AEAPTMS) onto the surface of DEAC-aC′ dots via PPSMI. Unreacted AEAPTMS was removed using GPC.…”

Section: Three-color Labeling Of Actin and Tubulin Network As Well As...mentioning

confidence: 99%

Antibody Functionalization of Ultrasmall Fluorescent Core–Shell Aluminosilicate Nanoparticle Probes for Advanced Intracellular Labeling and Optical Super Resolution Microscopy

et al. 2023

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Fluorescent labeling of cellular substructures is commonly performed using antibody–organic dye conjugates. Organic dyes do not exhibit ideal optical properties in terms of brightness and photostability, however, in particular when it comes to advanced optical super-resolution microscopy (SRM) applications. Here, we demonstrate the efficient conjugation of widely available secondary antibodies and cationic species to ultrasmall (sub-10 nm) fluorescent silica corepoly(ethylene glycol) shell (core–shell) aluminosilicate nanoparticles (aC′ dots) encapsulating different color dyes for specific targeting and high-quality fluorescence imaging of structures of the cytoskeleton (tubulin and actin) and nucleus, respectively. We show that the different color aC′ dots provide enhanced brightness and photostability relative to their parent dyes. As recently discovered, we further demonstrate that they exhibit photo-induced blinking with low ON–OFF duty cycles enabling optical SRM, for example, in the form of stochastic optical reconstruction microscopy (STORM), without the need for complex imaging setups or cocktails. After carefully optimizing Ab–aC′ dot conjugation as well as cell structure labeling protocols in fixed and permeabilized HeLa and MDA-MB-231 cells, we demonstrate three-color STORM and exemplify improved resolution compared to standard antibody–dye conjugates. This work paves the way to next-generation multifunctional optical probes based on ultrasmall silica nanoparticle platforms for advanced applications in bioimaging, nanomedicine, and beyond.

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“…Compared to the monomeric complex, the polymer exhibits similar subcellular distribution but remarkably lower (photo)cytotoxicity. Salvati, Maggioni, and co-workers have utilized a cationic PAMAM as the backbone for attaching ruthenium(II) complexes for PDT applications. , The resultant metallopolymer ( 149 ) shows more efficient cellular uptake in live HeLa cells compared to its zwitterionic counterpart 148b . It enters cells via an active uptake mechanism and undergoes trafficking along the endosomal/lysosomal compartments.…”

Section: Luminescent Transition Metal Conjugates For Bioimagingmentioning

confidence: 99%

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications

Lee,

2024

Chem. Rev.

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Luminescence imaging is a powerful and versatile technique for investigating cell physiology and pathology in living systems, making significant contributions to life science research and clinical diagnosis. In recent years, luminescent transition metal complexes have gained significant attention for diagnostic and therapeutic applications due to their unique photophysical and photochemical properties. In this Review, we provide a comprehensive overview of the recent development of luminescent transition metal complexes for bioimaging and biosensing applications, with a focus on transition metal centers with a d 6 , d 8 , and d 10 electronic configuration. We elucidate the structure−property relationships of luminescent transition metal complexes, exploring how their structural characteristics can be manipulated to control their biological behavior such as cellular uptake, localization, biocompatibility, pharmacokinetics, and biodistribution. Furthermore, we introduce the various design strategies that leverage the interesting photophysical properties of luminescent transition metal complexes for a wide variety of biological applications, including autofluorescence-free imaging, multimodal imaging, organelle imaging, biological sensing, microenvironment monitoring, bioorthogonal labeling, bacterial imaging, and cell viability assessment. Finally, we provide insights into the challenges and perspectives of luminescent transition metal complexes for bioimaging and biosensing applications, as well as their use in disease diagnosis and treatment evaluation.

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Light-Triggered Trafficking to the Cell Nucleus of a Cationic Polyamidoamine Functionalized with Ruthenium Complexes

Cited by 7 publications

References 59 publications

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities

Antibody Functionalization of Ultrasmall Fluorescent Core–Shell Aluminosilicate Nanoparticle Probes for Advanced Intracellular Labeling and Optical Super Resolution Microscopy

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications

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