Synthesis Of Cell-Targeted Carbon Dots-Mesoporous Silica Fluorescent Complex And Its Biological Application

Mesoporous silica nanoparticles(MSNs)are well known to possess not only little or no toxicity on account of common properties such as ease of functionalization chemistry,facile cell uptake,biodegradability and excellent biocompatibility,but also their distinctive features such as high specific surface area,large pore volume,tunable pore structure,and stable physicochemical properties in the past decades.Thus,the applications of MSNs have attracted scientists? great interest in biomedical field.MSNs have been intensively researched for targeting drug delivery,diagnosis,chemotherapy and many other considerable bioapplications due to a series of advantages in bioapplications.In recent twenty years,mesoporous nanoparticles have been functionalized by various imaging materials,including fluorescent proteins and organic dyes widely used in many biomedical fields,but their poor photobleaching property is not suitable for long-term and realtime bioimaging.Carbon quantum dots(CDs)have aroused intense interests by researchers and soon become a star material among a diversity of nanomaterials since its serendipitous discovery.An important advantage of CDs is that,carbon is generally not considered as a toxic element,unlike the semi-conductor quantum dots(QDs)containing heavy metals.Fluorescent CDs exhibit great potential in photocatalysis,solar cells,sensing and bioimaging due to their nontoxicity,biocompatibility,excellent chemical-and photo-stability as well as superior optical properties.Among the possible matrix materials for loading of CDs,the fluorescence nanocomposites of MSNs and CDs can be acted as nanocarriers.We synthesized two types of mesoporous silica with different fluorescence properties by two methods in this paper to combine biological imaging and targeted therapy.The contents of this paper are as follows:(1)We have developed a facile,low-cost and one-step microwave route for the synthesis of fluorescence mesoporous nanoparticles(FA-CDs-MSNs)with targeting property from a mixture of folic acid(FA)and MSNs.Through systematic investigations,we found that carbon-derived mesoporous nanoparticles had low toxicity,excellent fluorescence and targeting action.The fluorescence mesoporous nanoparticles were directly applied in cell imaging and targeted biological therapy.Such technology has also been employed as an important strategies to distinguish the cancer cell from normal cells.Moreover,targeted delivery can increase the bioavailability of drugs into tumor tissues and reduce the toxicity on normal tissues as well.Moreover,some researchs have be reported to synthesis CDs adopting FA as carbon source for targeting and detecting cancer cells.To verify the feasibility of these FA-CDs-MSNs for intracellular imaging and delivering drug in cancer chemotherapy.Doxorubicin(DOX),a typical anticancer drug,was efficiently loaded into FA-CDs-MSNs.Thus targeting of FA in the nanoparticle loaded with DOX could be a better approach for selectively target tumor tissues and inhibiting cancer cells.In this paper,the as-synthesized fluorescence mesoporous nanoparticles were conjugated with FA to construct a novel biocompatible nanoplatform for cell-targeting.With great biocompatibility,the MSNs with targeted property has the functions of cell imaging and controlling drug release.(2)We prepared NIR-MSNs through copolycondensation method.Then a biocompatible nanoplatform were constructed on the basis of amine-functionalized NIR-MSNs via surface modification of(3-Carboxypropyl)triphenylphospine(TPP).We obtained NIR-MSNs-TPP with a mitochondrial targeting property.The NIR-CDs were conjugated with 3-isocyanatopropyltriethoxysilane(IPTS)to obtain NIR-silane.Then the products was prepared through co-condensation of NIR-silane and TEOS.NIR-MSNs were functionalized with(3-aminopropyl)triethoxysilane(APTES)by using covalent binding with post-synthesis-grafting.TPP covalently bonded onto the surface of MSNs through the carboxyl group on the TPP and the amino group on the NIR-MSNs-NH2.As we know,the NIR-CDs also exhibit two-photon properties with both excitation and emission in the NIR regions.Futhermore,the NIR-CDs are verified to have very low cytotoxicity and show capabilities for two-photon fluorescence bioimaging.This allows the use of deep-penetrating and biologically friendly NIR light instead of low-penetrating and/or toxic visible or UV lights for applications.Some applications such as conventional photoactivation techniques are hampered by the limited penetration depth of the UV and visible lights.Here we describe a protocol for the use of NIR-MSNs.The NIR-CDs are coated with mesoporous silica for easy loading of the therapeutics.Remarkably,the as-prepared nanocomposite of MSNs and NIR-CDs could not only be potentially employed for deeptissue two-photon bioimaging,but also used as an effective carrier for delivery of drugs.Finally,the NIR-MSNs are confirmed to be easily conjugated with TPP,demonstrating promising targeted to deliver drugs.