Abstract:Nanomedicine-based combination therapy has sparked a growing interest in clinical disease treatment and pharmaceutical industry. In this study, a mitochondria-targeted and near-infrared (NIR) light-activable multitasking nanographene (i.e., GT/IR820/DP-CpG) was engineered to in situ trigger highly efficient "triple-punch" strategy of cancer photodynamic therapy, photothermal therapy, and immunotherapy. Modification of triphenylphosphonium on graphene made the vehicle specifically guide the NIR dye IR820 home t… Show more
“…The high lipophilicity of TPP with three aromatic rings and a positive charge on phosphorous enhanced the cell association and access to mitochondria. Further, the introduction of the immunostimulatory conjugate (i.e., cytosine−guanosine oligodeoxynucleotides) increased the production of proinflammatory cytokines (i.e., interleukin-6, tumor necrosis factor-α, and interferon-γ), thus, modulating the tumor immunogenicity [ 50 ]. From experimental data emerged that target nanophototherapeutics, generating ROS and heat, ultimately kill cancer cells by inducing mitochondrial collapse and irreversible cell apoptosis upon NIR laser irradiation and the target systems prompted much higher early apoptosis than non-target counterparts.…”
Section: Subcellular Localization Of Functional Graphene Nanomatermentioning
The paper reviews the network of cellular signaling pathways activated by Functional Graphene Nanomaterials (FGN) designed as a platform for multi-targeted therapy or scaffold in tissue engineering. Cells communicate with each other through a molecular device called signalosome. It is a transient co-cluster of signal transducers and transmembrane receptors activated following the binding of transmembrane receptors to extracellular signals. Signalosomes are thus efficient and sensitive signal-responding devices that amplify incoming signals and convert them into robust responses that can be relayed from the plasma membrane to the nucleus or other target sites within the cell. The review describes the state-of-the-art biomedical applications of FGN focusing the attention on the cell/FGN interactions and signalosome activation.
“…The high lipophilicity of TPP with three aromatic rings and a positive charge on phosphorous enhanced the cell association and access to mitochondria. Further, the introduction of the immunostimulatory conjugate (i.e., cytosine−guanosine oligodeoxynucleotides) increased the production of proinflammatory cytokines (i.e., interleukin-6, tumor necrosis factor-α, and interferon-γ), thus, modulating the tumor immunogenicity [ 50 ]. From experimental data emerged that target nanophototherapeutics, generating ROS and heat, ultimately kill cancer cells by inducing mitochondrial collapse and irreversible cell apoptosis upon NIR laser irradiation and the target systems prompted much higher early apoptosis than non-target counterparts.…”
Section: Subcellular Localization Of Functional Graphene Nanomatermentioning
The paper reviews the network of cellular signaling pathways activated by Functional Graphene Nanomaterials (FGN) designed as a platform for multi-targeted therapy or scaffold in tissue engineering. Cells communicate with each other through a molecular device called signalosome. It is a transient co-cluster of signal transducers and transmembrane receptors activated following the binding of transmembrane receptors to extracellular signals. Signalosomes are thus efficient and sensitive signal-responding devices that amplify incoming signals and convert them into robust responses that can be relayed from the plasma membrane to the nucleus or other target sites within the cell. The review describes the state-of-the-art biomedical applications of FGN focusing the attention on the cell/FGN interactions and signalosome activation.
“…However, RNA and DNA oligonucleotides, including MBs, are rapidly degraded under physiological conditions, and the negatively charged oligonucleotides are difficult to internalize into cancer cells; therefore, they have limited utility as therapeutic agents 11. Fortunately, the advent of nanotechnology has led to the development of different kinds of gene delivery systems, such as mesoporous silica nanoparticles 12, nanographene 13, PLGA-based nanoparticles 14, gold nanoparticles 15, and iron oxide nanoparticles. Such delivery systems are able to protect and transfer plasmid DNA 16, 17, oligonucleotides 18 and fluorescent probes 19 into living cells.…”
Background & Aims: The use of antisense oligonucleotide-based nanosystems for the detection and regulation of tumor-related gene expression is thought to be a promising approach for cancer diagnostics and therapies. Herein, we report that a cubic-shaped iron oxide nanoparticle (IONC) core nanobeacon is capable of delivering an HSP90α mRNA-specific molecular beacon (HSP90-MB) into living cells and enhancing T2-weighted MR imaging in a tumor model.Methods: The nanobeacons were built with IONC, generation 4 poly(amidoamine) dendrimer (G4 PAMAM), Pluronic P123 (P123) and HSP90-MB labeled with a quencher (BHQ1) and a fluorophore (Alexa Fluor 488).Results: After internalization by malignant cells overexpressing HSP90α, the fluorescence of the nanobeacon was recovered, thus distinguishing cancer cells from normal cells. Meanwhile, MB-mRNA hybridization led to enzyme activity that degraded DNA/RNA hybrids and resulted in downregulation of HSP90α at both the mRNA and protein levels. Furthermore, the T2-weighted MR imaging ability of the nanobeacons was increased after PAMAM and P123 modification, which exhibited good biocompatibility and hemocompatibility.Conclusions: The nanobeacons show promise for applicability to tumor-related mRNA detection, regulation and multiscale imaging in the fields of cancer diagnostics and therapeutics.
“…In vivo results demonstrated that GT/IR820/DP-CpG shows significant inhibition of tumor growth (tumor inhibition rate approximately 88%) which resulted from the combination of the photothermal effect of IR 820 and immunostimulatory activity of DP-CpG ( Fig. 5 ) [105] . Fig.…”
Section: Nanocarriers For Mitochondrial Targeting In Diagnosis and Treatment Of Cancermentioning
Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting.
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