An ideal nanotheranostic agent should be able to achieve efficient tumor accumulation, retention, and fast elimination after its theranostic functions exhausts. However, there is an irreconcilable contradiction on optimum sizes for effective tumor retention and fast elimination. Herein, a programmed size‐changeable nanotheranostic agent based on polyprodrug‐modified iron oxide nanoparticles (IONPs) and aggregation‐induced emission photosensitizer is developed for enhanced magnetic resonance imaging (MRI)‐guided chemo/photodynamic combination therapy. The nano‐sized theranostic agents with an initial diameter of about 90 nm can accumulate in tumor tissue through passive targeting. In the acidic tumor microenvironment, large aggregates of IONPs are formed, realizing enhanced tumor retention and MR signal enhancement. Under the guidance of MRI, light irradiation is applied to the tumor site for triggering the generation of reactive oxygen species and drug release. Moreover, after chemo/photodynamic combination therapy, the large‐sized aggregates are re‐dispersed into small‐sized IONPs for fast elimination, reducing the risk of toxicity caused by long‐term retention. Therefore, this study provides a promising size‐changeable strategy for the development of nanotheranostic agents.
The combination of chemotherapeutic drugs and reactive oxygen species (ROS) can improve cancer treatment outcome. Many ROS-generation strategies can specifically consume tumor-inherent oxygen and generate ROS, resulting in amplified ROS level and aggravated hypoxia. Therefore, the ROS generation strategy can integrate with prodrug activation strategy to realize synergetic therapy. In recent years, stimuli-responsive nanomedicines have been developed to realize the integration of ROS generation and prodrug activation. Triggered by a stimulus, nanomedicines can generate ROS at the tumor site, which can further activate the release of active drugs. In this review, we will summarize the latest progress of these nanomedicines and discuss the perspectives and challenges.
The combination of chemodynamic therapy (CDT) and chemotherapy has shown promise for achieving improved cancer treatment outcome. However, due to the lack of synergy rationale, simple one-plus-one combination therapy remains...
Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the β-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.
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