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Mitochondria are key organelles in mammalian cells whose dysfunctions are linked to various diseases. Drugs targeting mitochondrial proteins thus provide a highly promising strategy for potential therapeutics. Current methods of mitochondria-targeting delivery of small molecule drugs are available, but not suitable for macromolecules such as proteins (including antibodies). Herein, we report the first example of mitochondria-targeting intracellular delivery of native proteins (and antibodies) by using biodegradable silica nanoparticles (BS-NPs). Endowed with surface-modified triphenylphosphonium (TPP) and cell-penetrating poly(disulfide)s (CPD), these protein-loaded nanocapsules were capable of rapid intracellular uptake with minimal endolysosomal trapping, thus providing sufficient time for effective mitochondrial localization followed by glutathione-triggered biodegradation and mitochondrial release of native functional proteins to take part in further biological processes.
This article was published in the following journal.
Name: Angewandte Chemie (International ed. in English)
Intracellular compartment drug delivery is a promising strategy for the treatment of diseases. By this way, medicines can delivered to particular intracellular compartments. This maximizes the therape...
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Protein domains of approximately 120 amino acids that form two perpendicular anti-parallel beta sheets connected by a loop of variable length and a C-terminal amphipathic helix. PH domains occur in many INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS where they bind PHOSPHATIDYLINOSITOLS within the CELL MEMBRANE and INTRACELLULAR MEMBRANES, as well as proteins that include the Betagamma-subunits of HETEROTRIMERIC GTP-BINDING PROTEINS, and PROTEIN KINASE C. These interactions allow the targeting of proteins to different cellular compartments and SIGNAL TRANSDUCTION PATHWAYS.
Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available.
Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
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