Enhanced radiotherapy using photothermal therapy based on dual-sensitizer of gold nanoparticles with acid-induced aggregation.

The damaged DNA strands caused by radiotherapy (RT) can repair by themselves. A gold nanoparticles (GNPs) system with acid-induced aggregation was developed into a dual sensitizer owing to its high radioactive rays attenuation ability and enhanced photothermal heating efficiency after GNPs aggregation to achieve a combination therapy of RT and photothermal therapy (PTT). In this combination therapy, the formed GNP aggregates firstly showed a higher sensitize enhancement ratio (SER) value (1.52). Importantly, the self-repair of damaged DNA strands was inhibited by mild PTT through down-regulating the expression of DNA repair protein, thus resulting in a much higher SER value (1.68). Anti-tumor studies further demonstrated that this combination therapy exhibited ideal anti-tumor efficacy. Furthermore, the imaging signals of GNPs in computed tomography and photoacoustic were significantly improved following the GNPs aggregation. Therefore, a dual sensitizer with multimodal imaging was successfully developed and can be further applied as a new anti-tumor therapy.

Enhanced Radiosensitization by Gold Nanoparticles with Acid-Triggered Aggregation in Cancer Radiotherapy.

An ideal radiosensitizer holding an enhanced tumor retention can play an incredible role in enhancing tumor radiotherapy. Herein, a strategy of acid-triggered aggregation of small-sized gold nanoparticles (GNPs) system within tumor is proposed and the resulting GNPs aggregates are applied as a radiosensitizer in vitro and in vivo. The GNPs system with the acid-triggered aggregation achieves an enhanced GNPs accumulation and retention in cancer cells and tumors in the form of the resulted GNPs aggregates. As a consequence, the radiosensitization effect shows significant improvement in cancer radiotherapy, which is shown in the studies of DNA breakage and the comet assay, and the sensitizer enhancement ratio (SER) value of the GNPs system (1.730) with MCF-7 cancer cells is much larger than that of the single GNPs (1.16). In vivo antitumor studies reveal that the GNPs system also enhances the sensitivity of MCF-7 tumor xenograft to radiotherapy. Furthermore, the GNPs aggregates improve the signal of small GNPs in vivo photoacoustic imaging. This study provides a new strategy and insights into fabricating nanoaggregates to magnify the radiosensitive efficiency of nanosystems in cancer radiotherapy.

Enzyme-instructed self-assembly of a novel histone deacetylase inhibitor with enhanced selectivity and anticancer efficiency.

Nowadays, how to improve the selectivity of chemotherapy drugs and reduce their side effects is still a significant challenge for cancer research. Although enzyme-instructed self-assembly (EISA) has provided a promising approach for selective cancer therapy, the application of EISA is still suffering from requiring much higher concentrations for inhibiting cancer cells. Therefore, new strategies are needed to maximize the anticancer efficacy and preserve the selectivity of EISA. In this study, we rationally designed and synthesised a novel peptide-based prodrug molecule, NapGDFDFpYSV, combining EISA with the YSV anticancer peptide. The activity of the prodrug molecule was remarkably reduced by masking "Y" with a phosphoryl (-PO3) group and was recovered through dephosphorylation in situ by alkaline phosphatase (ALP) catalysis. The resulting monomer, NapGDFDFYSV, as a hydrogelator further self-assembled into the nanodrug on the cell surface, resulting in enhanced cellular uptake and selective high cytotoxicity to cells overexpressing ALP via action on histone deacetylase. Moreover, the required cell inhibition concentration of NapGDFDFpYSV was much lower than its critical micelle concentration (CMC), exhibiting outstanding advantages compared with separately used EISA without the anticancer peptide. Our study provides a new strategy to improve the cytotoxicity selectivity and bioactivity of chemotherapy drugs as well as the anticancer efficiency of EISA.

Acid-Triggered in Situ Aggregation of Gold Nanoparticles for Multimodal Tumor Imaging and Photothermal Therapy.

Photothermal agents with high photothermal transfer efficiencies in the near-infrared (NIR) region are important for enhanced photothermal therapy (PTT) of tumors. Herein, we developed a strategy for the acid-triggered in situ aggregation of a system based on peptide-conjugated gold nanoparticles (GNPs). In an acidic environment, the GNPs formed large aggregates in solution, in cell lysates, and in tumor tissues, as observed by transmission electron microscopy (TEM). As a consequence of the aggregation, their UV-vis absorbance in the NIR region was greatly increased, and laser irradiation of the GNPs resulted in a dramatic increase in the temperatures of solutions and tumors that contained the GNP system. When exposed to NIR irradiation, the aggregates formed by the GNP system under acidic conditions were capable of producing a sufficient level of hyperthermia to destroy cancer cells both in vitro and in vivo. Interestingly, the GNP aggregates showed enhanced properties in multiple imaging modalities, including computed tomography (CT), photoacoustic (PA), and photothermal (PT) imaging. Thus, we have developed a novel probe for enhanced multimodal tumor imaging. These findings prove that a strategy involving the acid-triggered in situ aggregation of a GNP system can increase the photothermal transfer efficiency for low to high energy conversion, thus boosting the therapeutic specificity and antitumor efficacy of PTT and facilitating multimodal imaging.

Complete Genome Sequence of Bacillus subtilis Strain CGMCC 12426, an Efficient Poly-γ-Glutamate Producer.

Bacillus subtilis CGMCC 12426 is an efficient producer of poly-γ-glutamate with regular stereochemistry. Here, the complete genome sequence of B. subtilis CGMCC 12426 is presented, which may facilitate the design of rational strategies for further strain improvements with industrial potential.

Suppression of rolling circle amplification by nucleotide analogs in circular template for three DNA polymerases.

Among wide applications of nucleotide analogs, their roles in enzyme catalytic reactions are significant in both fundamental and medical researches. By introducing analogs into circular templates, we succeeded in determining effects of four analogs on RCA efficiency for three different DNA polymerases. Results showed an obvious suppression effect for 2'-OMeRNA modification, which might be due to the size of the C2'-modified moieties. 2'-F RNA, LNA and PS had little interference, suggesting good analog candidates for application in RCA. Different polymerases and nucleobases made a little difference according to analogs we used. These results are useful for understanding polymerase catalytic mechanism and analogs applications in RCA reaction.