Programmed Nanoparticle‐Loaded Nanoparticles for Deep‐Penetrating 3D Cancer Therapy |
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Authors: | Jinhwan Kim Changshin Jo Won‐Gwang Lim Sungjin Jung Yeong Mi Lee Jun Lim Haeshin Lee Jinwoo Lee Won Jong Kim |
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Affiliation: | 1. Department of Chemistry, Pohang University of Science and Technology (POSTECH) and Center for Self‐assembly and Complexity, Institute for Basic Sciecne (IBS), Pohang, Korea;2. Department of Chemical Engineering and School of Environmental Science and Engineering, POSTECH, Pohang, Korea;3. School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang, Korea;4. Beamline Division, Pohang Light Source, Pohang, Korea;5. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea |
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Abstract: | Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting “nanoparticle‐loaded nanoparticles” to address the long‐lasting problem is reported for effective surface‐to‐core drug delivery in entire 3D tumors. The “nanoparticle‐loaded nanoparticle” is a silica nanoparticle (≈150 nm) with well‐developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)‐loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface‐to‐core tumor tissues, and finally (3) release a drug triggered by cancer‐characteristic pH gradients. The hierarchical “nanoparticle‐loaded nanoparticle” can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs. |
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Keywords: | deep penetration DNA engineering gold nanoparticle large‐pored mesoporous silica nanoparticle tumor pH gradient |
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