No abstract

A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM(-1) s(-1). To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues.

The design and development of a multifunctional and stimuli-responsive magnetic nanoparticle (MNP)-based drug delivery system has attracted great interest for the diagnosis and therapy of cancer. However, the effective incorporation of magnetic iron oxide nanoparticles into biomedical systems requires in vitro and in vivo stability, good biocompatibility, high loading efficacy, and controlled drug release. Surface-functionalized magnetic iron oxide nanoparticles created using engineered surface ligands have presented new strategies for the applications of MNP-based drug delivery systems in cancer imaging and therapy to overcome these obstacles. Moreover, the development and design of stimuli-responsive ligands has been combined with the engineering of multiple physicochemical features into MNPs to enhance the performance of the MNP-based delivery system.

MicroRNAs, which can interfere with the translation of target mRNAs, caught a particular interest as their functions are related to human cancers. As the most common cancer in women, cervical cancer remains one of the leading cancer-related causes of death. In this study, we performed an integrative miRNA analysis to identify prognosis related miRNAs for cervical cancer. In addition, we developed an n-miRNA expression signature (risk score) to comprehensively assess the prognosis of cervical cancer, especially for survival time. Furthermore, we performed target predictions and functional enrichment analyses for the identified miRNAs to investigate their potential role in the development of disease. Univariate Cox regression models were used to assess the association between miRNAs and prognosis of cervical cancer. Three miRNAs were identified to be significantly associated with survival time of patients. Hsa-miR-3154 and hsa-miR-7-3 were significantly associated with shortened survival time and more death cases, whereas expression level of hsa-miR-600 was significantly associated with prolonged survival time. The function enrichment analysis showed the target genes of poor prognosis related miRNAs were mainly enriched in the mTOR pathway, whereas target genes of positive prognosis related miRNAs were mainly enriched in the AMPK pathway. In summary, a 3-miRNA expression signature was identified which can predict cervical cancer patient survival. The potential functions of this 3-miRNA expression signature and individual miRNAs as prognostic targets of cervical cancer were revealed by this study. Furthermore, these findings may have important implications in the understanding of the potential therapeutic method for the cervical cancer patients.