Enzymatic Nanosphere-to-Nanofiber Transition and Autophagy Inducer Release Promote Tumor Chemotherapy.

Chemotherapy has remained an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies are proposed to address these issues, yet their therapeutic outcomes are still far from satisfactory. Thus, it is urgent to develop novel strategies to promote tumor chemosensitivity while reducing toxic side effects of chemotherapeutics. Herein, employing a rationally designed peptide conjugate Nap-Phe-Phe-Lys(SA-AZD8055)-Tyr(H2 PO3 )-OH (Nap-AZD-Yp), a novel approach of simultaneous intracellular nanofiber formation and autophagy inducer release is proposed for selectively sensitizing tumor to chemotherapy. Upon sequential catalyses of alkaline phosphatase and carboxylesterase, Nap-AZD-Yp undergoes nanosphere-to-nanofiber transition accompanied by autophagy inducer AZD8055 release in cancer cells. Cell experiments show enhanced endocytosis of anticancer drug doxorubicin and inhibition of cell migration due to the intracellular nanofiber formation. The released AZD8055 further activates excessive autophagy of cancer cells, sensitizing them to chemotherapy. Animal experiment results suggest Nap-AZD-Yp can significantly enhance the therapeutic effects of doxorubicin on tumors while mitigate its toxic adverse effects on normal tissues. It is anticipated that the "smart" concept in this work c be widely employed to develop novel combinational therapies for the treatment of cancers and other diseases in near future.

Symptom clusters and quality of life among patients with chronic heart failure: A cross-sectional study.

AIM: This study aimed to identify symptom clusters among patients with chronic heart failure (HF) and examine their independent relationships with quality of life (QoL). METHODS: A descriptive cross-sectional design was adopted, and 201 Chinese participants were recruited. Their symptom profiles and QoL were assessed using the Memorial Symptom Assessment Scale-Heart Failure and Minnesota Living with Heart Failure Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Pearson's correlation analysis and multiple regression analysis were conducted to examine their independent relationships with QoL. RESULTS: Six distinct symptom clusters were identified: the fatigue, dyspneic, discomfort, congestive, ischemic, and emotional symptom clusters. These six symptom clusters accounted for 57.508% of the variance in patient symptom experiences and were positively related to their overall QoL. Moreover, the fatigue (ß = .317, p < .001), dyspneic (ß = .228, p < .001), congestive (ß = .363, p < .001), and emotional (ß = .200, p < .001) symptom clusters independently predicted QoL. CONCLUSION: The six symptom clusters that were identified in this study and the relationships that they shared with QoL are expected to inform future approaches to symptom management. Interventions that target these symptom clusters will improve the QoL of patients with HF.

Covalently Conjugated Hydrogelators for Imaging and Therapeutic Applications.

In recent years, research on supramolecular hydrogels for biomedical applications developed rapidly by covalently conjugating their hydrogelators with functional moieties including therapeutic agents and imaging probes. Such conjugation can not only endow hydrogels with specific functions but also enhance the performance of the functional moieties. Therefore, these evolutionary conjugates may create a great leap for the application of supramolecular hydrogels in clinical scenarios, especially in a bioimaging or a sustained drug release system. In order to draw inspiration from the rapid advancement in this field and establish cornerstones for innovative exploration in the follow-up research, herein, we review the recent advances of the covalently conjugated hydrogelators and their biomedical applications in imaging and therapies. Besides, we provide our views on the remaining challenges and a perspective on future trends of conjugated hydrogelators.