Tuning the cellular uptake and cytotoxicity properties of oligonucleotide intercalator-functionalized mesoporous silica nanoparticles with human cervical cancer cells HeLa.
A series of organically functionalized, MCM-41 type mesoporous silica nanoparticle materials (PAP-LP-MSN and AP-PAP-MSN) with different pore sizes (5.7 nm and 2.5 nm, respectively) were synthesized and characterized. We selectively decorated the exterior particle surface of PAP-LP-MSN and the interior pore surface of AP-PAP-MSN with an oligonucleotide intercalating phenanthridinium functionality. While phenanthridinium itself is a cell membrane impermeable molecule, we demonstrated that both phenanthridinium-immobilized PAP-LP-MSN and AP-PAP-MSN materials could indeed be internalized by live human cervical cancer cells (HeLa). We discovered that the PAP-LP-MSN nanoparticles with the phenanthridium groups located on the exterior surface were able to bind to cytoplasmic oligonucleotides, such as messenger RNAs, of HeLa cells resulting in severe cell growth inhibition. In contrast, the cytotoxicity of AP-PAP-MSN, where the same oligonucleotide intercalating molecules were anchored inside the pores, was significantly lowered upon the endocytosis by HeLa cells. We envision that this approach of combining the selective functionalization of the two different surfaces (exterior particle and interior pore surfaces) with morphology control of mesoporous silica nanoparticles would lead to a new generation of nanodevices with tunable biocompatibility and cell membrane trafficking properties for many biomedical applications.
Vivero-Escoto
Juan L
JL
Department of Chemistry, U.S. Department of Energy Ames Laboratory, Iowa State University, Ames, IA 50011-3111, USA. ivivero@iastate.edu
Slowing
Igor I
II
Lin
Victor S-Y
VS
D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D009841:Oligonucleotides; D012822:Silicon Dioxide