Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.

Imaging-guided photothermal therapy (PTT) by combination of imaging and PTT has been emerging as a promising therapeutic method for precision therapy. However, the development of multicomponent nanoplatforms with stable structures for both PTT and multiple-model imaging remains a great challenge. Herein, we synthesized monodisperse Au-FeC Janus nanoparticles (JNPs) of 12 nm, which are multifunctional entities for cancer theranostics. Due to the broad absorption in the near-infrared range, Au-FeC JNPs showed a significant photothermal effect with a 30.2% calculated photothermal transduction efficiency under 808 nm laser irradiation in vitro. Owing to their excellent optical and magnetic properties, Au-FeC JNPs were demonstrated to be advantageous agents for triple-modal magnetic resonance imaging (MRI)/multispectral photoacoustic tomography (MSOT)/computed tomography (CT) both in vitro and in vivo. We found that Au-FeC JNPs conjugated with the affibody (Au-FeC-Z) have more accumulation and deeper penetration in tumor sites than nontargeting JNPs (Au-FeC-PEG) in vivo. Meanwhile, our results verified that Au-FeC-Z JNPs can selectively target tumor cells with low cytotoxicity and ablate tumor tissues effectively in a mouse model. In summary, monodisperse Au-FeC JNPs, used as a multifunctional nanoplatform, allow the combination of multiple-model imaging techniques and high therapeutic efficacy and have great potential for precision theranostic nanomedicines.

BackgroundAlthough an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer.Materials and methodsOne hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed.ResultsTAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis.ConclusionThis study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.

Nitric oxide (NO) induces a multitude of antitumor activities, encompassing the induction of apoptosis, sensitization to chemo-, radio-, or immune-therapy, and inhibition of metastasis, drug resistance, angiogenesis, and hypoxia, thus attracting much attention in the area of cancer intervention. To improve the precise targeting and treatment efficacy of NO, a glutathione (GSH)-sensitive NO donor (1,5-bis­[(l-proline-1-yl)­diazen-1-ium-1,2-diol-O 2-yl]-2,4-dinitrobenzene, BPDB) coordinates with iron ions to form the nanoscale coordination polymer (NCP) via a simple precipitation and then partial ion exchange process. The obtained Fe­(II)-BNCP shows desirable solubility, biocompatibility, and circulation stability. Quick NO release triggered by high concentrations of GSH in tumor cells improves the specificity of NO release in situ, thus avoiding side effects in other tissues. Meanwhile, under high concentrations of H2O2 in tumors, Fe2+ ions in BPDB-based NCP, named Fe­(II)-BNCP, exert Fenton activity to generate hydroxyl radicals (·OH), which is the main contribution for chemodynamic therapy (CDT). In addition, ·O2 – generated by the Haber-Weiss reaction of Fe2+ ions with H2O2 can quickly react with NO to produce peroxynitrite anion (ONOO–) that is more cytotoxic than ·O2 – or NO only. This synergistic NO-CDT effect has been proved to retard the tumor growth in Heps xenograft ICR mouse models. This work not only implements a synergistic effect of NO-CDT therapy but also offers a simple and efficient strategy to construct a coordination polymer nanomedicine via rationally designed prodrug molecules such as NO donors.

Two-dimensional (2D) materials have attracted tremendous interest as fluorescence quenchers of dye-labeled biomolecules for application in biosensing. Metal-organic framework (MOF) nanosheets, as a new type of 2D material, have rarely been studied as bioanalytical platforms. Herein, we synthesize a series of ultrathin lanthanide-based MOF (MOF-Ln) nanosheets as a dye-labeled aptamer platform. The fluorescence quenching or recovery on the MOF-Ln nanosheets is determined by the charge properties (positive or negative) of the labeled fluorophores. The negatively charged fluorophores experience a fluorescence 'turn-down followed by turn-down' process, whereas the positively charged fluorophores experience a fluorescence 'turn-down followed by turn-up' process. The interesting fluorescence quenching properties of the MOF-Ln nanosheets make them an excellent two-color sensing platform for the intracellular detection of biomolecules. NPG Asia Materials (2017) 9, e354; doi:10.1038/am.2017.7; published online 10 March 2017 INTRODUCTION Two-dimensional (2D) nanomaterials have been attracting extensive research interest due to their unique physical and chemical properties, as well as their potential scientific and technological applications in the fields of gas storage, sensing, electronics, energy conversion and storage, and electrocatalysis. 1 In the area of biomedical applications, 2D nanosheets with an extremely high surface area, such as graphene and its derivative graphene oxide, have been successfully used for biomedical imaging, drug delivery and cancer therapy. 2,3 Other emerging nanosheets (for example, MoS 2 , WS 2 and MnO 2 ) with a good fluorescence-quenching ability also exhibit selective adsorption affinity toward single-stranded DNA (ssDNA) versus double-stranded DNA (dsDNA). [4][5][6][7] These results have inspired studies to exploit the potential biological applications of novel 2D nanosheets. Very recently, 2D metal-organic framework (MOF) thin films or nanosheets have been successfully synthesized and exfoliated by several groups. [8][9][10] Their potential biological applications remain to be explored.MOFs are a fascinating class of functional materials that have been extensively studied for applications in gas storage, 11 catalysis, 12 separation 13 and sensing. 14 MOFs are certainly very promising for fabricating multifunctional luminescent sensors, because both the metal and the ligand units can provide platforms for generating luminescence and some guest molecules loaded on the MOFs can also emit or induce luminescence. 14 A variety of MOFs have been already

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Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.

BackgroundCancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors.Patients and methodsTumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed.ResultsThe CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5%) were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%). Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth.ConclusionThe fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.