title: Loading of an anti-cancer drug into mesoporous silica nano-channels and its subsequent release to DNA.
abstract: Mesoporous silica nano-channel (MCM-41) based molecular switching of a biologically important anticancer drug, namely, ellipticine (EPT) has been utilized to probe its efficient loading onto MCM-41, and its subsequent release to intra-cellular biomolecules, like DNA. By exploiting various spectroscopic techniques (like, steady state fluorescence, time-resolved fluorescence and circular dichroism), it has been shown that EPT can be easily translocated from MCM-41 to DNA without using any external stimulant. Blue emission of EPT in a polar aprotic solvent, i.e., dichloromethane (DCM), completely switches to green upon loading inside MCM-41 due to the conversion from a neutral to a protonated form of the drug inside nano-pores. Powder X-ray diffraction (PXRD), N2gas adsorption and confocal fluorescence microscopy results confirm the adsorption of EPT inside the nano-pores of MCM-41. Here, the lysozyme (Lyz) protein has been utilized as a pore blocker of MCM-41 in order to prevent premature drug release. Interestingly, EPT is released to DNA even from the EPT-MCM-Lyz composite system, and results in intensification of green fluorescence. Electron microscopy results reveal the formation of a distinctive garland kind of morphology involving MCM-41 and DNA probably through non-covalent interactions, and this is believed to be responsible for the DNA assisted release of drug molecules from silica nano-pores. Confocal laser scanning microscopy (CLSM) imaging revealed that EPT-MCM is successfully internalized into the HeLa cervical cancer cells and localized into the nucleus. Cell viability assay results infer that EPT-MCM and EPT-MCM-Lyz showed much improved efficacy in HeLa cancer cells compared to free ellipticine.
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India. p.hazra@iiserpune.ac.in.
authors: Raj Kumar
authors: RK
authors: Koninti
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India. p.hazra@iiserpune.ac.in.
authors: Sandeep
authors: S
authors: Palvai
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India. p.hazra@iiserpune.ac.in.
authors: Sagar
authors: S
authors: Satpathi
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India. p.hazra@iiserpune.ac.in.
authors: Sudipta
authors: S
authors: Basu
authors: Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Maharashtra, India. p.hazra@iiserpune.ac.in.
authors: Partha
authors: P
authors: Hazra
mesh_terms: D000327:Adsorption; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004247:DNA; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D043942:Nanotubes; D016062:Porosity; D012822:Silicon Dioxide; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D012822:Silicon Dioxide; D004247:DNA