Functionalized Nanomaterials Applied In Fluorescence Imaging And Targeted Therapy For Human Lung Cancer Cells

Nanomaterials have been applied in a broad variety of biomedical field like biomolecules detection,targeted drug delivery and tumor therapy,due to their excellent properties including the tunable morphology and size,unique physicochemical and optical characters,easily surface modification.In this dissertation,various nanometarials including inorganic and natural products and their derivative were prepared,followed by application in the detection of H2S in living lung cancer cells,targeted drug delivery and therapy.The details were described as follows:1.Considering the urgent need to explore multifunctional drug delivery systems for overcoming multidrug resistance,we prepared a new nano-carbon material Q-Graphene as a nanocarrier for killing drug-resistant lung cancer cells.Attributing to the introduction of hyaluronic acid(HA)and rhodamine B isothiocyanate(RBITC),the Q-Graphene based drug delivery system was endowed with dual-function of targeted drug delivery and fluorescence imaging.Additionally,doxorubicin(DOX),as a model drug was loaded on the surface of Q-Graphene via ?-? stacking.Interestingly,the fluorescence of DOX was quenched by Q-Graphene due to its strong electron-accepting capability and a significant recovery of fluorescence was observed while DOX was released from Q-Graphene.Due to the RBITC labelling and the effect of fluorescence quenching/restoring of Q-Graphene,the uptake of nanoparticles and intracellular DOX release could be tracked.Overall,a highly promising multifunctional nano-platform was developed for tracking and monitoring targeted drug delivery for efficiently killing drug-resistant cancer cells.2.In this paper,we proposed a natural derived protein cage based pH-responsive delivery system for intracellular prodrug controlled release.The drug delivery system was based on apoferritin as delivery vehicle to encapsulate anticancer drug daunomycin(DN)and alleviate the side effect.The hydrophobic drug DN was encapsulated into the interior of apoferritin by the hydrophobic channels of the cage swelling at slight acidic pH and electrostatic adsorption.The negatively charged poly-L-aspartic acid(PLAA)was further introduced into the apoferritin to absorb the positively charged DN.The mixture of PLAA and DN easily flew into the apoferritin cage and stably stored at physiological fluids.PLAA protected the leakage of DN and encapsulated sufficient amount of drug molecules in the cage.To specifically target the tumor cells,the surface of apoferritin was modified with hyaluronic acid which could bind to the overexpressed HA-receptor CD44 on A549 cell,while MRC-5 cell was negative expression.This unique protein based drug delivery platform using the apoferritin cage showed great potential therapeutic administration of the anti-cancer agents.3.Based on the self-assembly strategy,two kinds of one-dimentional nanotubes(FA-PepT-TCPP?FA-PepT-DNS)were obtained by using three kinds of biomimetic peptides labeled with different ligands.Unlike peptides,peptoids were composed of N-substituted glycine monomer instead of the a-carbon.More importantly,the peptidase/proteinase-resistance was highly improved which protected the premature of drug molecules,as well as chemical and thermal stability.Due to the FRET effect between DNS and DOX,both of their fluorescence were quenched after loading DOX to the nanotubes.The intracellular release of DOX was observed with the fluorescence recovery of DNS and DOX under the acid microenvironment of cancer cells.Besides,synergistic therapy was achieved by combinating the photodynamic therapy of FA-PepT-TCPP and the chemotherapy of DOX.More than half of H1299 cells were killed in a very low concentration of FA-PepT-TCPP(0.312 ?M),which illustrated the killing efficiency was enhanced significantly.4.Hydrogen sulfide as a gas signaling molecule plays an important role in diverse human physiological and pathological processes.However,due to the volatility and diffusible properties of H2S in biological systems,it is very difficult to implement a precise assay of H2S.Compared to the destructive instrumental methods,assays based on fluorescence probes contribute to a noninvasive and real-time detection of H2S in living cells.In this work,we presented a turn-on fluorescent probe based on dye-functionalized Au nanorods(NRs)@silica for sensitive and selective detection of H2S in vitro by virtue of their plasmon-enhanced fluorescence effect.Silica matrix was used to coat the Au NRs to prevent them from the biological cytotoxicity.The effects of different silica shell thickness on fluorescent enhancement were explored and approximately 5-fold fluorescence enhancement was observed with a silica thickness of 22 nm and a detection of limit of 17 nM was achieved.In addition,visualization of exogenous and endogenous H2S in living cells was validated.