TY - JOUR
T1 - Loading of an anti-cancer drug into mesoporous silica nano-channels and its subsequent release to DNA
AU - Koninti, Raj Kumar
AU - Palvai, Sandeep
AU - Satpathi, Sagar
AU - Basu, Sudipta
AU - Hazra, Partha
N1 - Publisher Copyright:
©2016 The Royal Society of Chemistry.
PY - 2016/11/21
Y1 - 2016/11/21
N2 - 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), N2 gas 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.
AB - 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), N2 gas 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.
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U2 - 10.1039/c6nr06285g
DO - 10.1039/c6nr06285g
M3 - Article
C2 - 27775145
AN - SCOPUS:84994619710
VL - 8
SP - 18436
EP - 18445
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 43
ER -