Autophagy inhibition mediated via an injectable and NO-releasing hydrogel for amplifying the antitumor efficacy of mild magnetic hyperthermia.

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

Electrospun Scaffolds are Not Necessarily Always Made of Nanofibers as Demonstrated by Polymeric Heart Valves for Tissue Engineering.

In the last 30 years, there are ≈60 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of ≈3 µm (named as "oligo-micro fiber") are more appropriate for tissue engineering scaffolds owing to their better cell infiltration ability caused by larger pores with available nuclear deformation. To further increase pore sizes, electrospun poly(ε-caprolactone) (PCL) scaffolds are fabricated using latticed collectors with meshes. Fiber orientation leads to sufficient mechanical strength albeit increases porosity. The latticed scaffolds exhibit good biocompatibility and improve cell infiltration. Under aortic conditions in vitro, the performances of latticed scaffolds are satisfactory in terms of the acute systolic hemodynamic functionality, except for the higher regurgitation fraction caused by the enlarged pores. This hierarchical electrospun scaffold with sparse fibers in macropores and oligo-micro fibers in filaments provides new insights into the design of tissue engineering scaffolds, and tissue engineering may provide living heart valves with regenerative capabilities for patients with severe valve disease in the future.