Journal
BIOMATERIALS
Volume 39, Issue -, Pages 249-259Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.10.079
Keywords
Microfluidics; Nanocomposite; Porous silicon; Acetalated dextran; Combination chemotherapy
Funding
- Academy of Finland [252215, 256394]
- University of Helsinki Funds
- Biocentrum Helsinki
- European Research Council under the European Union's Seventh Framework Programme [31089]
- Finnish Cultural Foundation for Postdoc Poohi Grant
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An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control. The release kinetics of all the payloads was predominantly controlled by the decomposition rate of the outer AcDX matrix. To facilitate the intracellular drug delivery, a nona-arginine cell-penetrating peptide (CPP) was chemically conjugated onto the surface of the nanocomposites by oxime click chemistry. Taking advantage of the significantly improved cell uptake, the proliferation of two breast cancer cell lines was markedly inhibited by the CPP-functionalized multidrug-loaded nanocomposites. Overall, this nano-in-nano PSi@polymer composite prepared by the microfluidic self-assembly approach is a universal platform for nanoparticles encapsulation and precisely controlled combination chemotherapy. (C) 2014 Elsevier Ltd. All rights reserved.
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