Journal
ACS NANO
Volume 6, Issue 5, Pages 3954-3966Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn300149c
Keywords
silica nanoparticle; nanoconjugates; chemotherapeutics; nanomedicine; drug delivery; cancer therapy; tumor penetration; cell uptake; nanoparticle biodistribution
Categories
Funding
- NIH [1DP2OD007246-01, 1R21CA152627]
- NIH National Cancer Institute Alliance for Nanotechnology in Cancer 'Midwest Cancer Nanotechnology Training Center' [R25 CA154015A]
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Drug-containing nanoparticles (NPs) with monodisperse, controlled particle sizes are highly desirable for drug delivery. Accumulating evidence suggests that NPs with sizes less than 50 nm demonstrate superior performance in vitro and in vivo. However, it is difficult to fabricate monodisperse, drug-containing NPs with discrete sizes required for studying and characterizing edging relationships among particle size, biologic processing, and therapeutic functionality. Here, we report a scalable process of fabricating drug-silica conjugated nanoparticles, termed drug-silica nanoconjugates (drug-NCs), which possess monodisperse size distributions and desirable particle sizes as small as 20 nm. We find that 20 nm NCs are superior to their 50 and 200 nm NC analogues by 2-5- and 10-20-fold, respectively, with regard to tumor accumulation and penetration and cellular Internalization. These fundamental findings underscore the importance and necessity of further miniaturizing nanomedicine size for optimized drug delivery applications.
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