Programmed Nanoparticle‐Loaded Nanoparticles for Deep‐Penetrating 3D Cancer Therapy

• Published in: Advanced materials (Weinheim) 2018-07, Vol.30 (29), p.e1707557-n/a
• Main Authors: Kim, Jinhwan, Jo, Changshin, Lim, Won‐Gwang, Jung, Sungjin, Lee, Yeong Mi, Lim, Jun, Lee, Haeshin, Lee, Jinwoo, Kim, Won Jong
• Format: Article
• Language: English
• Subjects: Blood circulation; Blood vessels; Cancer; deep penetration; Deoxyribonucleic acid; DNA; DNA engineering; Drug delivery systems; Gold; gold nanoparticle; large‐pored mesoporous silica nanoparticle; Nanoparticles; Penetration; Silicon dioxide; tumor pH gradient; Tumors
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.201707557

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. Programmed nanoparticle‐loaded nanoparticles, comprising large‐pored silica nanoparticles and DNA‐modified gold nanoparticles, exhibit sequential dynamic behavior for cancer therapy with three stages operated by DNA transition: preferential accumulation in the cancerous region, deep penetration into the 3D cancer tissues, and intracellular specific anticancer drug release.