Small interfering RNA (siRNA) therapeutics have shown tremendous potential for the treatment of a range of diseases, but there is still a need for novel siRNA delivery materials. Here, we introduce... Show moreSmall interfering RNA (siRNA) therapeutics have shown tremendous potential for the treatment of a range of diseases, but there is still a need for novel siRNA delivery materials. Here, we introduce M12L24 cages as siRNA delivery agents. We used four functionalized build-ing blocks to form M12L24 nanocages. Dynamic light scattering showed that well-defined 130 nm nanocage/siRNA assemblies formed with positive zeta potentials. Cell-specific siRNA-mediated green fluorescent protein (GFP) silencing, controlled by the metal used for nanocage formation, was obtained. A Pt12L24 nanocage was highly effective in delivering siRNA to U2OS cells but showed little efficiency for HeLa cells. The less stable Pd12L24 nanocage derived from the same building block displayed effective GFP silencing for HeLa cells but not for U2OS cells. The ease of prepara-tion and the ability to tune the binding strength, together with the specific siRNA delivery efficiency depending on the building blocks and metals, show potential for future siRNA delivery applications. Show less
There is an increasing interest in the application of metal-organic cages (MOCs) in a biomedicinal context, as they can offer non-classical distribution in organisms compared to molecular... Show moreThere is an increasing interest in the application of metal-organic cages (MOCs) in a biomedicinal context, as they can offer non-classical distribution in organisms compared to molecular substrates, while revealing novel cytotoxicity mechanisms. Unfortunately, many MOCs are not sufficiently stable under in vivo conditions, making it difficult to study their structure-activity relationships in living cells. As such, it is currently unclear whether MOC cytotoxicity stems from supramolecular features or their decomposition products. Herein, we describe the toxicity and photophysical properties of highly-stable rhodamine functionalized platinum-based Pt2L4 nanospheres as well as their building blocks under in vitro and in vivo conditions. We show that in both zebrafish and human cancer cell lines, the Pt2L4 nanospheres demonstrate reduced cytotoxicity and altered biodistribution within the body of zebrafish embryos compared to the building blocks. We anticipate that the composition-dependent biodistribution of Pt2L4 spheres together with their cytotoxic and photophysical properties provides the fundament for MOC application in cancer therapy. Show less
