Temperature Treatment of Highly Porous Zirconium-Containing Metal–Organic Frameworks Extends Drug Delivery Release

• DOI: 10.1021/jacs.7b01451
• Publication Date: 2017-05-16T10:54:29Z
• Authors: Michelle H. Teple...; Marcus Fantham; Peng Li; Timothy C. Wang; Joshua P. Mehta; Laurence J. Young; Peyman Z. Moghadam; Joseph T. Hupp; Omar K. Farha; Clemens F. Kaminski; David Fairen-Jimenez
• Keywords: Temperature; Antineoplastic Agents; 02 engineering and technology; 3. Good health; Drug Liberation; Drug Delivery Systems; Microscopy, Electron, Scanning; Humans; Zirconium; 0210 nano-technology; Porosity; Metal-Organic Frameworks; HeLa Cells

Utilizing metal-organic frameworks (MOFs) as a biological carrier can lower the amount of active pharmaceutical ingredient (API) required in cancer treatments to provide more efficacious therapy. In this work, we have developed temperature treatment process for delaying release model drug compound from pores NU-1000 and NU-901, while taking care utilize these MOFs' large pore volume size achieve exceptional loading percentages over 35 wt %. Video-rate super-resolution microscopy reveals movement MOF particles when located outside cell boundary, their subsequent immobilization taken up by cell. Through use optical sectioning structured illumination (SIM), captured high-resolution 3D images showing uptake HeLa cells 24 h period. We found that addition into does not affect rate Endocytosis analysis revealed MOFs are internalized transport inhibiting caveolae-mediated pathway significantly reduced cellular MOFs. Encapsulation an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic acid (α-CHC), produced loadings 81 % demonstrated efficacy at killing beyond burst effect.