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• W2463282839 abstract "The development of sophisticated nanoplatforms for in vivo targeted delivery of therapeutic agents to solid tumors has the potential for not only improving therapeutic efficacy but also minimizing systemic toxicity. However, the currently low delivery efficiency (about 1% of the injected dose) and the limited tumor penetration of nanoparticles remain two major challenges. Here we report a class of functionalized, long-circulating, and ultrasmall gold nanocarriers (5 nm gold core and 20 nm overall hydrodynamic diameter) for improved drug delivery and deep tumor penetration. By using doxorubicin as a model drug, our design also includes a pH-sensitive hydrazone linkage that is stable at neutral or slightly basic pH but is rapidly cleaved in the acidic tumor microenvironments and intracellular organelles. With a circulation halftime of 1.6 days, the small particle size is an important feature not only for efficient extravasation and accumulation via the enhanced permeability and retention (EPR) effect, but also for faster nanoparticle diffusion and improved tumor penetration. In xenograft animal models, the results demonstrate that up to 8% of the injected nanoparticles can be accumulated at the tumor sites, among the highest nanoparticle delivery efficiencies reported in the literature. Also, histopathological and direct visual examinations reveal dark-colored tumors with deep nanoparticle penetration and distribution throughout the tumor mass. In comparison with pure doxorubicin which is known to cause considerable heart, kidney, and lung toxicity, in vivo animal data indicate that this class of functionalized and ultrasmall gold nanoparticles indeed provides better therapeutic efficacies with no apparent toxicity in vital organs." @default.
• W2463282839 created "2016-07-22" @default.
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• W2463282839 date "2016-07-05" @default.
• W2463282839 modified "2023-10-16" @default.
• W2463282839 title "Functionalized, Long-Circulating, and Ultrasmall Gold Nanocarriers for Overcoming the Barriers of Low Nanoparticle Delivery Efficiency and Poor Tumor Penetration" @default.
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• W2463282839 doi "https://doi.org/10.1021/acs.bioconjchem.6b00224" @default.
• W2463282839 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27341302" @default.
• W2463282839 hasPublicationYear "2016" @default.
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