Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist (r1 = 4.25 mM-1 s-1) used in clinic, the PC/Ad-PEG2000-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity (r1 = 11.62 mM-1 s-1) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG2000-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo. Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.

Recent progress in the applications of gold-based nanoparticles towards tumor-targeted imaging and therapy.

Cancer death rate remains high all over the world, scientists are paying increasing attention to meet the requirements for precise diagnosis and therapy. Therefore, early diagnosis and active treatment can effectively improve the five-year survival rate of patients. In recent years, gold-based nanomaterials have received increasing attention in medical fields due to their excellent biocompatibility, low toxicity and unique properties. In addition, because of the inherent nature of gold nanomaterials including for computed tomography (CT), fluorescence/optical imaging (FI/OI), surface enhanced Raman spectroscopy imaging (SERS), photoacoustic imaging (PAI) and photothermal therapy (PTT), various gold nanomaterials were developed as theranostic nanoplatforms. In this review, we summarized the latest developments of nanomaterials in imaging and combined therapy, and the prospects for the future application of gold-based theranostic nanoplatforms were also proposed.

Neferine induces apoptosis by modulating the ROS­mediated JNK pathway in esophageal squamous cell carcinoma.

Current treatments for esophageal squamous cell carcinoma (ESCC) have limited efficacy. Therefore, the development of novel therapeutic targets to effectively manage the disease and boost survival rates is imperative Neferine, a natural product extracted from Nelumbo nucifera (lotus) leaves, has been revealed to inhibit the growth of hepatocarcinoma, breast cancer and lung cancer cells. However, its effect on ESCC is unknown. In the present study, it was revealed that neferine exerted anti­proliferative effects in ESCC. It was also revealed that it triggered arrest of the G2/M phase and enhanced apoptosis of ESCC cell lines. Moreover, its ability to trigger accumulation of reactive oxygen species (ROS) and activate the c­Jun N­terminal kinase (JNK) pathway was demonstrated. Further study revealed how N­acetyl cysteine (NAC), a ROS inhibitor, attenuated these effects, demonstrating that ROS and JNK inhibitors mediated a marked reversal of neferine­triggered cell cycle arrest and apoptosis in ESCC cells. Finally, it was revealed that neferine was involved in the inhibition of Nrf2, an antioxidant factor. Collectively, these findings demonstrated the antitumor effect of neferine in ESCC, through the ROS­mediated JNK pathway and inhibition of Nrf2, indicating its potential as a target for development of novel and effective therapeutic agents against ESCC.

Role of miRNA in transformation from normal tissue to colorectal adenoma and cancer.

Although many modalities can be used to prolong the remission of colorectal cancer (CRC), early diagnosis is essential to improve the therapeutic outcomes. The conventional ways of diagnosing and monitoring the progresses from adenoma to CRC are colonoscopy and fecal occult blood test (FOBT). However, colonoscopy is expensive and invasive; while the FOBT is not sensitive. miRNAs may be a new modality to monitor the transition from adenoma to CRC. We reviewed publications of miRNA profile differences from colorectal normal mucosa (NM) to adenoma, and to CRC and tried to find the roles of miRNA in these transitions. This review also highlighted the possibility of serum miRNAs as markers for monitoring these transitions. The miRNA profiles are different from normal colorectal mucosa to adenoma and to CRC. The miRNAs may have pro- or anti-CRC effects through oncogenes such as c-Met and KRAS. Others may interfere with the immune system. More interestingly, some miRNAs are continuously increased from NM to adenoma and to CRC; others, such as miRNA-30b, are consequently decreased. The literature shows that miRNAs are involved in the whole process of the colorectal carcinogenesis. The miRNAs may be the biomarkers in monitoring the transition from adenoma to CRC.