Many nanosized particulate systems are being developed as intravascular carriers to increase the levels of therapeutic agents delivered to targets, with the fewest side effects1,2. The surface of these carriers is often functionalized with biological recognition molecules for specific, targeted delivery. However, there are a series of biological barriers in the body3,4,5 that prevent these carriers from localizing at their targets at sufficiently high therapeutic concentrations5,6. Here we show a multistage delivery system that can carry, release over time and deliver two types of nanoparticles into primary endothelial cells. The multistage delivery system is based on biodegradable and biocompatible mesoporous silicon particles that have well-controlled shapes, sizes and pores. The use of this system is envisioned to open new avenues for avoiding biological barriers and delivering more than one therapeutic agent to the target at a time, in a time-controlled fashion.
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We thank the University of Texas at Austin for the use of the semiconductor cleanroom facilities, M. Landry for excellent graphical support, A. Jimenez for laboratory assistance, and T. Tanaka and B. Godin for helpful suggestions. These studies were supported by the following grants: DoDW81XWH-04-2-0035 Project 16 (M.F., M.C., X.L., E.T., R.B.), NASA SA23-06-017 (M.F., M.C., X.L., R.B., E.T., J.T., A.L., B.K.P.), State of Texas, Emerging Technology Fund (M.F., X.L., R.B., K.P.), and the National Institutes of Health (NIH) NCI 1R21CA1222864-01 (M.F., M.C., F.R.). The authors would like to recognize the contributions and support from the Alliance for NanoHealth (ANH).
Commercialization rights on intellectual property presented in this paper have been acquired by Leonardo Biosystems Inc., from the title holder, the University of Texas Health Science Center in Houston. M.F. is the founding scientist of Leonardo Biosystems, and hereby discloses a financial interest in the company.
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Tasciotti, E., Liu, X., Bhavane, R. et al. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotech 3, 151–157 (2008). https://doi.org/10.1038/nnano.2008.34
Nano-Micro Letters (2022)
Clinical and Translational Medicine (2019)