Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy.

Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.

The correlation between IGF-II and Bcl-2 expression in colorectal adenocarcinoma.

Our aim for this study was to investigate the correlation and clinical significance between the expression of IGF-II and Bcl-2 in colorectal adenocarcinoma, especially in terms of the metastasis of colorectal adenocarcinoma. Sixty paraffin embedded samples of colorectal adenocarcinoma were selected, and fifteen normal colorectal tissues were used as controls. IGF-II mRNA was detected using in situ hybridization, and the expression of Bcl-2 along with the proliferating cell nuclear antigen (PCNA) protein was detected through immunohistochemistry. The TUNEL assay was used to detect apoptosis. Specimens with a positive cell ratio less than 30% were defined as negative. The levels of IGF-II mRNA and the Bcl-2 protein were significantly higher in colorectal adenocarcinoma (39.64 ± 7.38% and 30.74 ± 7.22%, respectively) than in normal colorectal tissues (22.56 ± 4.21% and 12.17 ± 1.94%, respectively) (P < 0.01). The levels were related to Dukes' stage and lymph node metastases, but were unrelated to patient age, gender, tumor site, tumor size, and tumor differentiation. Also, a negative correlation was observed between IGF-II mRNA and Bcl-2 protein (P < 0.05) during Dukes' stages. In addition, a positive correlation between IGF-II mRNA and PCNA or apoptosis, as well as a negative correlation between Bcl-2 and apoptosis were observed (P < 0.01). There was no correlation between Bcl-2 and PCNA (P > 0.05). The patients detected as IGF-II mRNA (+) and Bcl-2 (-) showed the worst prognosis. The expression of IGF-II and Bcl-2 was correlated with the clinical manifestation of colorectal adenocarcinoma; thus, the assessment of both IGF-II and Bcl-2's status will provide important information regarding the diagnosis and prognosis of colorectal adenocarcinoma.