Functionalized Nanomaterials Applied In Drug Delivery And Therapy For Human Cancer Cells

At present,chemotherapy is an important way to treat cancer and has been applied in a broad variety of cancers.However,the high toxic side effect still is the main challenge the traditional chemotherapy faced.How to improve the curative effect of drugs and reduce their side effects is the key point of cancer therapy.With the vigorous development of nanotechnology,functionalized nanomaterials have been successfully applied in biomedical fields for drug delivery and cancer therapy.Benefiting from their unique physical,chemical and optical properties of nanomaterials,nanomaterials-based drug delivery system can accurately kill tumor cells,reducing the damage to normal tissues.Moreover,the integration of nanomaterials-based drug delivery with multiple treatment methods can greatly improve the therapeutic efficiency toward cancer,showing great potential for the clinical treatment of cancer.Here,a series of nano-drug delivery systems were constructed and applied to achieve multimodal therapy toward cancer cells.The details were described as follows:1.It is reported that ZnO quantum dots(ZnO QDs)are less toxic,easy to synthesize,and can display a response to acid.Based on the excellent properties of ZnO QDs and their coordination with the anticancer drug doxorubicin(DOX),a biodegradable and pH-sensitive "ZnO-DOX" drug delivery system was constructed for the chemotherapy of lung tumor cells.In addition,a targeting ligand,hyaluronic acid(HA),was conjugated to ZnO QDs in order to bind to A549 lung cancer cells specifically,which could targeted delivery DOX to lung cancer cells and reduce the damage to normal cells.After cellular internalization,ZnO QDs showed the ability of rapid dissolution to Zn2+ under mildly acidic conditions in tumor,which could trigger selective drug release inside cancer cells.Moreover,Zn2+ exhibited synergistic cytotoxicity effect with DOX and could improve the therapeutic index.2.Utilizing the adjustable morphology and size of nanomaterials,along with the high permeability and retention effect(EPR effect)of solid tumors,we demonstrated a "ZnO nanocluster-DOX" drug delivery system and investigated its application for the chemotherapy of lung cancer cells.The nanoclusters were cross-linked by dicarboxyl-terminated poly(ethylene glycol)(PEG),showing high stability and biocompatibility in physiological fluids.The clustered ZnO QDs not only were capable of loading a large quantity of doxorubicin(DOX)via multiple interactions,but also could accumulated in tumor tissue selectively by EPR effect,increasing the concentration of drugs in tumor cells.In addition,ZnO QDs can be decomposed into Zn2+ under acidic conditions,thus the synthesized ZnO cluster carriers would be completely decomposed under the weak acidic stimulation after delivered to tumor cells,which can be metabolize quickly and avoid the retention and toxic side effects in the body.3.Photodynamic therapy(PDT)has become a new technology for cancer therapy due to its advantages,such as non-invasive,small injury and high selectivity,but the hydrophobicity and instability of photosensitizer lead to low therapy efficiency.Three-dimensional dendritic mesoporous silicon(DMSNs)possesses high load rate,large pore size and easy degradation in vivo,which can effectively delivery photosensitizer to tumor cells and improve the efficiency of PDT.In addition,as PDT is highly dependent on local oxygen concentration,its therapy efficiency is limited by the phenomenon of tumor hypoxia.Based on the high concentration of hydrogen peroxide in hypoxic tumors,platinum nanoparticles(Pt NPs)can effectively catalyze the decomposition of hydrogen peroxide and produce oxygen.The functionalized "Pt-DMSNs-TPP/Ce6" delivery system was fabricated taking lung cancer cell A549 as model cells,which was applied in high-efficiency PDT for hypoxic tumors.As mitochondria is very sensitive to singlet oxygen,the modification of mitochondrial targeted ligand TPP can enhance the effect of PDT.This work reported a new therapy strategy that used functionalized nanomaterials for PDT of hypoxic tumors and was combined with mitochondrial targeting,which would bring new insight for tumor PDT.4.Photothermal therapy(PTT),as another new method of tumor treatment,using nano-photothermal agent to convert the energy of near infrared light into heat energy,achieves killing the cancer cells efficiently and reducing the damage to the normal tissue.Here,we prepared mesoporous carbon nanomaterials(OMCN)with photothermal property.PEG chain was introduced on the surface of OMCN to enhance their water solubility and stability in biological systems.After loading drugs DOX and modifying target ligand HA,the functionalized "OMCNP-DOX" drug delivery system with high drug loading capacity has been constructed for combined chemo-/photothermal-targeted therapy of lung cancer cells.In this system,the photothermal conversion efficiency of OMCNP was high,showing good cell killing ability under near infrared irradiation.To prevent the early leakage of drugs,drug loaded-OMCNP were caped using acid-decomposable ZnO QDs.Due to the specific tumor targeting mediated by HA,this drug delivery system exhibited efficient accumulation in tumor and strong tumor burning effect.Importantly,the "ZnO lid" can break down in the weak acidic microenvironment of the tumor to achieve acid-responsive drug release.The results of experiments in vitro showed that the system had tumor targeting ability,high photothermal conversion efficiency and achieved combined chemo-/photothermal therapy for lung cancer.5.IR-780 Iodide(IR780),as a fat-soluble cationic anthocyanins dye,is not only a good fluorescent probe for tumor living imaging,but also can produce both light heat and singlet oxygen under single near infrared laser irradiation,which can be used for combined PTT/PDT of tumor.In order to solve the hydrophobicity,high concentration self-quenching of IR780 and to improve the effect of light therapy,a one-dimensional peptoid nanotubes(PepIR-DOX)delivery system was constructed using self-assembled strategy to realize the co-load of IR780 and anticancer drug DOX for multimodal therapy(chemotherapy/PTT/PDT)of malignant glioma cell U87MG.Peptoid,as a natural product derivative nanomaterial,not only shows good biocompatibility,but also has excellent chemical,physical and physiological stability.By optimizing the assembly ratio of IR780,the final self-assembled peptoid nanotubes could delivery hydrophobic IR780 to tumor cells effectively,solved the problem of self-quenching of photosensitizer and improved the effect of phototherapy.In addition,the high specific surface area of peptoid nanotubes could effectively delivery DOX,which realized synergistic chemo-phototherapy of U87MG cells,resulting in high therapeutic efficiency.