摘要：A eukaryotic cell contains thousands of proteins that regulate its cellular function; delivering functional proteins into cells to rectify cellular functions holds great promise for treatment of various diseases, especially cancers. In this context, ribonuclease （RNase）, an enzyme that breaks down ribonucleic acid （RNA）, has great potential for cancer therapy. However, its therapeutic application is hampered by poor intracellular delivery efficiency and inhibition by ubiquitous intracellular RNase inhibitors. In this work, by designing and synthesizing RNase nano-conjugates by in situ atom transfer radical polymerization （ATRP）, we demonstrate a simple solution to address both challenges. Compared with native RNase, nano-conjugates exhibit significantly enhanced intracellular delivery efficiency, inhibitor resistance, and a near five-fold increase in cytotoxicity. This work provides a novel platform for delivery of therapeutic proteins for cancer therapy and other applications.

摘要：Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer *** protein toxins have long been known as the primary virulence factor(s)for a variety of pathogenic bacteria and are the most powerful human *** the other hand,it has been well documented that urokinase-type plasminogen activator(uPA)and urokinase plasminogen activator receptor(uPAR),making up the uPA system,are overexpressed in a variety of human tumors and tumor cell *** expression of uPA system is highly correlated with tumor invasion and *** exploit these characteristics in the design of tumor cell-selective cytotoxins,two prominent bacterial protein toxins,i.e.,the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion *** uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA systemexpressing tumor cells,thereby killing these *** article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal *** is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

摘要：One method of cancer therapy is to utilize nano-antenna for thermal *** this method,the electromagnetic waves emitted from the nano-antenna are absorbed by the tissue and lead to heating of cancer *** temperature of cancer cells reaches a threshold,they will begin to *** this purpose,an L-shaped frame nano-antenna(LSFNA) is designed to introduce into the biological ***,the radiation characteristics of the LSFNA such as near and far-field intensities,directivity,and sensitivity to its gap width are studied to the optimization of the *** bio-heat and Maxwell equations are solved using the finite element *** prevent damage to healthy tissues in this method,the antenna radiation must be completely controlled and performed ***,penetration depth,special absorption rate,temperature distribution,and the fraction of tissue necrosis are analyzed in the biological *** is why the design and optimization of the nano-antennas as a radiation source is ***,a pulsed source is used to excite the ***,focusing and efficiency of the nano-antenna radiation on the cancer cell is tuned using an adjustable liquid crystal *** focus of this lens is changing under an electric field applied to its surrounding cathode.

摘要：Cytosolic protein delivery techniques are of great importance for cell biology,biotechnology and protein drug *** design of carriers with robust efficiency in cytosolic protein delivery is *** account provides a progress report of polymeric carriers for this purpose in our *** the past years,we have developed several types of functionalized polymers for cytosolic protein and peptide delivery by engineering polymers with ligands such as guanidinium,boronate,coordination ligands and *** designed polymers showed improved protein/peptide binding affinities,and successfully delivered various cargo proteins into the cytosol of living cells,while maintaining their *** addition,the polymers showed potent efficiencies in the delivery of tumor antigens,therapeutic peptides,toxins and antioxidant proteins in *** hope these polymers could be translated for protein delivery in the treatment of various diseases in the future.

摘要：Targeted drug delivery has been widely explored for efficient tumor therapy with desired efficacy but minimized side effects. It is widely known that large numbers of DNA-toxins, such as doxorubicin, genes, reactive oxygen species, serving as therapeutic agents, can result in maximized therapeutic effects via the interaction directly with DNA helix. So after cellular uptake, these agents should be further delivered into cell nuclei to play their essential roles in damaging the DNA helix in cancer ceils. Here, we demonstrate the first paradigm estabJished in our laboratory in developing nucle- ar-targeted drug delivery systems （DDSs） based on MSNs for enhanced therapeutic efficiency in the hope of speeding their translation into the ctinics. Firstly, nuclear-targeting DDSs based on MSNs, capable of intranuclear accumulation and drug release therein, were designed and constructed for the first time, resulting in much enhanced anticancer effects both in vitro and in vivo. Such an MSNs-based and nuclear-targeted drug/agent delivery strategy was further applied to overcome multidrug resistance （MDR） of malignant tumors, intra-nuclearly deliver therapeutic genes, photosensitizers, radio-enhancement agents and photothermal agents to realize efficient gene therapy, photodynamic therapy, radiation therapy and photothermal therapy, respectively.

摘要：Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110-145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.

摘要：To investigate the efficiency of polyamidoamine dendrimer grafted carbon nanotube （dendrimer-CNT） mediated entrance of anti-survivin oligonucleotide into MCF-7 cells, and its effects on the growth of MCF-7 cells. Methods： Antisense survivin oligonucleotide was anchored onto polyamidoamine dendrimer grafted carbon nanotubes to form dendrimer-CNT-asODN complex and the complex was characterized by Zeta potential, AFM, TEM, and 1% agarose gel electrophoresis analysis. Dendrimer-CNT-asODN complexes were added into the medium and incubated with MCF-7 cells. MTT method was used to detect the effects of asODN and dendrimer-CNT-asODN on the growth of MCF-7 cells. TEM was used to observe the distribution of dendrimer-CNT-asODN complex within MCF-7 cells. Results： Successful synthesis of dendrimer-CNT-asODN complexes was proved by TEM, AFM and agarose gel electrophoresis. TEM showed that the complexes were located in the cytoplasm, endosome, and lysosome within MCF-7 cells. When dendrimer-CNT-asODN （1.0 μmol/L） and asODN （1.0 μmol/L） were used for 120 h incubation, the inhibitory rates of MCF-7 cells were （28.22±3.5）% for dendrimer-CNT-asODN complex group, （9.23±0.56）% for only asODN group, and （3.44±0.25）% for dendrimer-CNT group. Dendrimer-CNT-asODN complex at 3.0 μmol/L inhibited MCF-7 cells by （30.30±10.62）%, and the inhibitory effects were in a time- and concentration-dependent manner. Conclusion： Dendrimer-CNT nanoparticles may serve as a gene delivery vector with high efficiency, which can bring foreign gene into cancer cells, inhibiting cancer cell proliferation and markedly enhancing the cancer therapy effects.

摘要：The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone ***,we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine(CQ)-loaded polydopamine nanoparticles(PPA/CQ)for efficient treatment of bone tumors via breaking the vicious *** nanoparticles were efficiently accumulated to the bone tissues,especially the osteolytic lesions around *** released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor(TNF)receptor-associated receptor 3 to attenuate the osteolysis in bone *** the other hand,CQ blocked the autophagy in cancer cells,resulting in improved photothermal killing of cancer ***,the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and *** work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.