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Lysosomes have become an important target for anticancer therapeutics because lysosomal cell death bypasses the classical caspase-dependent apoptosis pathway, enabling the targeting of apoptosis- and drug-resistant cancers. However, only a few small molecules-mostly repurposed drugs-have been tested so far, and these typically exhibit low cancer selectivity, making them suitable only for combination therapies. Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells. This selectivity results from distinct pH-dependent aggregation events, starting from the formation of small, endocytosis-prone clusters at cell surfaces and ending with the formation of large and well-ordered nanoparticle assemblies and crystals inside cancer lysosomes. These assemblies cannot be cleared by exocytosis and cause lysosome swelling, which gradually disrupts the integrity of lysosomal membranes, ultimately impairing lysosomal functions and triggering cell death.
This article was published in the following journal.
Name: Nature nanotechnology
Fluorescence imaging is a powerful tool in biomedical research. It has been frequently used to uncover or better understand physiological mechanisms in disease-related processes such as cancer. The ma...
Binary alloy nanoparticles were fabricated by two combinatorial methods: (I) co-sputtering from elemental targets into the ionic liquid 1-butyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)imide [...
Pathogenesis hallmarks for tuberculosis (TB) are the mycobacterium tuberculosis (Mtb) escape from phagolysosomal destruction and limited drug delivery into host cells. Several nanomaterials can ent...
lthough co-crystallization has provided a promising platform to develop new organic optoelectronic materials, it is still a big challenge to purposely design and achieve specific optoelectronic proper...
The functionalization of gold nanoparticles is commonly based on the use of thiol groups for the anchoring of organic ligands. To functionalize gold nanoparticles with mixed layers in defined proporti...
Silver nanoparticles are one of most nanoparticles use nowadays in the research area because it has specific physical and chemical properties, in medical fields silver nanoparticles can in...
The purpose of this study is to determine whether oral topic silver nanoparticles are effective to reduce potential pathogen microbial loads in mechanical ventilation patients.
Endarterectomy of the carotid artery procedure will be performed at Sheba Medical center vascular surgery department, followed by fixation and histology. Tissues will then be transferred t...
Due to the great toxicity of chemotherapeutic drugs to both the healthy and cancerous area, the efficient targeting could be of great benefit for a patient with advanced or metastatic tumo...
The nanoparticles (NP) are defined as particles whose size is no greater than 100 nanometers. However, their impact on health remains little evaluated. Placental transfer of NP has been p...
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver.
A layer of protein coating adsorbed by NANOPARTICLES upon entry into PLASMA or other protein-containing biological fluids, which affects how nanoparticles are internalized by cells and cleared from the body.
Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...