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. Author manuscript; available in PMC: 2018 Sep 1.
Published in final edited form as: Drug Discov Today. 2017 May 6;22(9):1336–1350. doi: 10.1016/j.drudis.2017.04.021

Figure 4.

Figure 4

Cellular and subcellular delivery strategies for bone disease therapy. (a) Aptamer-functionalized lipid nanoparticles (LNPs) for the anabolic treatment of osteoporosis (OP). (i) LNPs functionalized with aptamer (CH6) for osteoblast (OB)-specific delivery of casein kinase-2 interacting protein-1 (CKIP-1) small interfering (si)RNA. (ii) CH6-LNP-siRNA can preferentially accumulate in bone tissue (femur), indicated by fluorescent intensity of Cy3-labeled siRNA. (iii) The 3D microarchitecture of proximal tibia was improved 14 weeks after the addition of CH6-LNP-siRNA in OP rats. Scale bar = 1 mm. (b) Bone microenvironment-targeted delivery of bortezomib for myeloma therapy. (i) Poly(L-lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticles functionalized with alendronate (Alen) for bone-specific targeting. (ii) Intracellular uptake of Alexa647-labeled nanoparticles in GFP+MM1S cells. Scale bar = 5 Mm (iii) Pretreatment of bortezomib-load PLGA-PEG-Alen nanoparticles reduced tumor burden in mice after 29 days. (c) Silica nanoparticles promoted osteogenesis via the stimulation of autophagy. (i) Silica nanoparticles interact with autophagy factors (p62) to stimulate autolysosome formation. (ii) TEM images of silica nanoparticles (NP1) localized in autolysosome structures. Scale bar = 1 Mm (iii) Alizarin red S staining of MC3T3-E1 OBs after 14 days of treatment with NP1. (d) Targeting of miR-29b-loaded gold nanoparticles (GNPs) to the endoplasmic reticulum (ER) for promoting osteogenic differentiation. (i) GNPs functionalized with polyethylenimine (PEI) for intracellular delivery of miR-29b. (ii) Immunofluorescence staining of nuclei (blue), ER (green), and Cy3-miR-29b (red), illustrating the localization of GNPs/Cy3-miR-29b to the ER of hMSCs. Scale bar = 25 Mm. (iii) TEM images of GNPs agglomerated in the ER of hMSCs after 14 days. Scale bar = 1 Mm. (iv) Alizarin red staining of MC3T3-E1 OBs after 21 days of treatment with GNPs/miR-29b. Reproduced, with permission, from [125] (a), [129] (b), [131] (c), and [138] (d).