Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

Durfee, Paul N.; Lin, Yu-Shen; Dunphy, Darren R.; Muñiz, Ayşe J.; Butler, Kimberly S.; Humphrey, Kevin R.; Lokke, Amanda J.; Agola, Jacob O.; Chou, Stanley S.; Chen, I-Ming; Wharton, Walker; Townson, Jason L.; Willman, Cheryl L.; Brinker, C. Jeffrey

doi:10.1021/acsnano.6b02819

Title: Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

Journal Article · Fri Jul 15 00:00:00 EDT 2016 · ACS Nano

DOI:https://doi.org/10.1021/acsnano.6b02819· OSTI ID:1340264

Durfee, Paul N. ^[1]; Lin, Yu-Shen ^[2]; Dunphy, Darren R. ^[3]; Muñiz, Ayşe J. ^[4]; Butler, Kimberly S. ^[3]; Humphrey, Kevin R. ^[5]; Lokke, Amanda J. ^[4]; Agola, Jacob O. ^[3]; Chou, Stanley S. ^[6]; Chen, I-Ming ^[7]; Wharton, Walker ^[8]; Townson, Jason L. ^[2]; Willman, Cheryl L. ^[8]; Brinker, C. Jeffrey ^[9]

Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Chemical and Biological Engineering; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials, Advanced Materials Lab.
Univ. of New Mexico, Albuquerque, NM (United States). Internal Medicine; Oncothyreon, Inc., Seattle, WA (United States)
Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials, Advanced Materials Lab.
Univ. of New Mexico, Albuquerque, NM (United States). Health Sciences Center, Biochemistry and Molecular Biology
Vanderbilt Univ., Nashville, TN (United States). Dept. of Biomolecular Engineering
Sandia National Lab. (SNL-CA), Livermore, CA (United States). Advanced Materials Lab.
Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Pathology; Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center
Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Pathology; Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center
Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Chemical and Biological Engineering; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials, Advanced Materials Lab.; Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Advanced Materials Lab.; Univ. of New Mexico, Albuquerque, NM (United States). Comprehensive Cancer Center

Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here in this research, we investigate mesoporous silica nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayer composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSN and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index <0.1) on MSN cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and reverified their monodispersity and stability. Then, using intravital imaging in the CAM, we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. In conclusion, overall we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and other disseminated disease.

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Research Organization:: Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Science Foundation (NSF); US Air Force Office of Scientific Research (AFOSR)

Grant/Contract Number:: AC04-94AL85000; FA 9550-1-14-066; 1344298; DBI-1266377; UO1 CA151792-01

OSTI ID:: 1340264

Report Number(s):: SAND-2016-12522J; 649845

Journal Information:: ACS Nano, Vol. 10, Issue 9; ISSN 1936-0851

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 150 works

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