CONSPECTUS Non-viral vectors, typically based on cationic lipids or polymers, are preferred due to safety concerns with viral vectors. So far, non-viral vectors can proficiently transfect cells in culture, but obtaining efficient nanomedicines is far from evident. To overcome the hurdles associated with non-viral vectors is significant for improving delivery efficiency and therapeutic effect of nucleic acid. The drawbacks include the strong interaction of cationic delivery vehicles with blood components, uptake by the reticuloendothelial system (RES), toxicity, targeting ability of the carriers to the cells of interest, and so on. PEGylation is the predominant method used to reduce the binding of plasma proteins with non-viral vectors and minimize the clearance by RES after intravenous administration. The nanoparticles that are not rapidly cleared from the circulation accumulate in the tumors due to the enhanced permeability and retention effect, and the targeting ligands attached to the distal end of the PEGylated components allow binding to the receptors on the target cell surface. Neutral or anionic liposomes have been also developed for systemic delivery of nucleic acids in experimental animal model. Designing and synthesizing novel cationic lipids and polymers, and binding nucleic acid with peptides, targeting ligands, polymers, or environmentally sensitive moieties also attract many attentions for resolving the problems encountered by non-viral vectors. The application of inorganic nanoparticles in nucleic acid delivery is an emerging field, too. Recently, different classes of non-viral vectors appear to be converging and the features of different classes of non-viral vectors could be combined in one strategy. More hurdles associated with efficient nucleic acid delivery therefore might be expected to be overcome. In this account, we will focus on these novel non-viral vectors, which are classified into multifunctional hybrid nucleic acid vectors, novel membrane/core nanoparticles for nucleic acid delivery and ultrasound-responsive nucleic acid vectors. The systemic delivery studies are highlighted. Finally, we bring forward the prospect for nucleic acid delivery. We think a better understandings of the fate of the nanoparticles inside the cell and of the interactions between the parts of hybrid particles will lead to a delivery system suitable for clinical use. We also underscore the value of sustained release of nucleic acid and presume making vectors targeted to cells with sustained release in vivo should be an interesting research challenge.

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Tumor-associated macrophage (TAM)-related chronic inflammation and interleukin-6 (IL-6) contribute to the progression of nasopharyngeal carcinoma (NPC). In this study, we characterized TAMs and IL-6 expression in 212 biopsied NPC and 119 non-tumor nasopharyngeal epithelium (NPE) tissues by tissue array. In comparison with that in the NPE tissues, more TAM infiltrates and a higher density of IL-6 expression were detected in NPC tissues, which were associated with the poor survival of NPC patients. In contrast, little or no LPLUNC1, a regulator of inflammation, expression was detected in NPC tissues, and the levels of LPLUNC1 expression in the NPC were associated negatively with the numbers of TAMs and the levels of IL-6 expression, but positively with the survival of NPC patients. Induction of LPLUNC1 overexpression in NPC cells mitigated lipopolysaccharide (LPS)-induced IL-6, IL-8, tumor necrosis factor-α and IL-1β expression or treatment of THP-1 macrophages with LPLUNC1 inhibited spontaneous and LPS-induced IL-6 expression in vitro. IL-6-promoted NPC cell proliferation in a dose- and time-dependent manner, accompanied by increasing cyclin D1 and Bcl-2 expression and the Stat3 activation, but inhibiting Bax and p21 expression. Induction of LPLUNC1 overexpression inhibited NPC cell proliferation, induced NPC cell arrest, promoted NPC cell apoptosis even after IL-6 stimulation and inhibited the growth of implanted NPC tumors in vivo, which were associated with decreasing cyclin D1 and Bcl-2 expression and the Janus kinase 2 (JAK2)/Stat3 activation, but enhancing Bax and p21 expression. These results suggest that LPLUNC1 can inhibit inflammation and NPC growth by downregulating the Stat3 pathway.

SummaryMicroRNAs (miRNAs) are small noncoding RNAs that are involved in various diseases, including cancer. In the present study, we found that miR-216b was downregulated in nasopharyngeal carcinoma (NPC) cell lines and specimens. Decreased expression of miR216b was directly related to advanced clinical stage and lymph node metastasis. miR-216b levels correlated inversely with levels of KRAS protein during nasopharyngeal tumorigenesis. Furthermore, we demonstrated that miR-216b can bind to the 39 untranslated region (UTR) of KRAS and inhibit expression of the KRAS protein. Both in vitro and in vivo assays revealed that miR-216b attenuated NPC cell proliferation, invasion and tumor growth in nude mice. miR-216b exerts its tumor suppressor function through inhibition of the KRAS-related AKT and ERK pathways. Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in NPC.

BackgroundAn increasing number of studies have implicated the microbiome in certain diseases, especially chronic diseases. In this study, the bacterial communities in the sputum of pulmonary tuberculosis patients were explored. Total DNA was extracted from sputum samples from 31 pulmonary tuberculosis patients and respiratory secretions of 24 healthy participants. The 16S rRNA V3 hyper-variable regions were amplified using bar-coded primers and pyro-sequenced using Roche 454 FLX.ResultsThe results showed that the microbiota in the sputum of pulmonary tuberculosis patients were more diverse than those of healthy participants (p<0.05). The sequences were classified into 24 phyla, all of which were found in pulmonary tuberculosis patients and 17 of which were found in healthy participants. Furthermore, many foreign bacteria, such as Stenotrophomonas, Cupriavidus, Pseudomonas, Thermus, Sphingomonas, Methylobacterium, Diaphorobacter, Comamonas, and Mobilicoccus, were unique to pulmonary tuberculosis patients.ConclusionsThis study concluded that the microbial composition of the respiratory tract of pulmonary tuberculosis patients is more complicated than that of healthy participants, and many foreign bacteria were found in the sputum of pulmonary tuberculosis patients. The roles of these foreign bacteria in the onset or development of pulmonary tuberculosis shoud be considered by clinicians.