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. Author manuscript; available in PMC: 2017 Apr 27.
Published in final edited form as: Small. 2016 Jan 18;12(16):2173–2185. doi: 10.1002/smll.201502119

Figure 2.

Figure 2

A) Schematic diagram depicting the successive steps of the multivalent binding [1], internalization [2], endosomal escape [3] and delivery of cargo to the nucleus [4] of peptide targeted protocells. B) Hyperspectral confocal imaging of targeted delivery of multicomponent cargo by protocells to Hep3B cells for 12 hours at 37°C. Alexa Fluor 532-labeled mesoporous silica cores (yellow) were loaded with calcein, dsDNA oligonucleotide (magenta), Red Fluorescent Protein (orange), and CdSe/ZnS quantum dots (teal). Cargos were sealed in the cores by fusion of Texas Red-labeled DOPC liposomes (red). The calcein and dsDNA oligonucleotide were modified with a nuclear localization signal and show accumulation in the nucleus by 12 hours, while the RFP and the quantum dots remain in the cytosol. Scale bars=20μm. C) Left axis (bars in grey and black): The percentage of multidrug resistant positive (MDR+) Hep3B hepatocellular carcinoma cells and normal hepatocytes that remained viable after exposure to free doxorubicin (DOX), targeted-protocell encapsulated DOX, liposomal DOX, targeted-protocells containing a cocktail of chemotheraputics or liposomes containing a cocktail of chemotherapeutics for 24 hours at 37°C at the LC90 value for free DOX. Right axis (bars in red): The percentage of MDR+ Hep3B cells that remain viable after exposure to free doxorubicin (DOX), protocell encapsulated DOX, liposomal DOX, targeted-protocells containing a cocktail of chemotheraputics or liposomes containing a cocktail of chemotherapeutics for 24 hours at 37°C at the LC50 value for free DOX. D) Confocal microscopy images of Hep3B hepatacellular carcinoma cells and normal hepatocytes after exposure to an excess peptide targeted protocells loaded with an anti-cyclin siRNA cocktail for 1 or 48 hours at 37°C. Cells were fix and then imaged by confocal microscopy, protocells are shown in white, cyclins in green and nuclei in blue. Scale bar=20μm . E) Induction of apoptosis by exposure to peptide targeted protocells loaded with an anti-cyclin siRNA cocktail. Cells were classified for early apoptosis (annexin V positive) or late apoptosis (annexin V and Propidium Iodide positive). A, B and C adapted with permission from Ashley 2011.[5] D and E adapted with permission from: Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers. Carlee E. Ashley, Eric C. Carnes, Katharine E. Epler, David P. Padilla, Genevieve K. Phillips, Robert E. Castillo, Dan C. Wilkinson, Brian S. Wilkinson, Cameron A. Burgard, Robin M. Kalinich, Jason L. Townson, Bryce Chackerian, Cheryl L. Willman, David S. Peabody, Walker Wharton, and C. Jeffrey Brinker. ACS Nano 2012 6 (3), 2174–2188. Copyright 2012 American Chemical Society.