High porosities, large surface areas, and tunable functionalities made metal-organic frameworks (MOFs) as effective carriers for drug delivery. One of the most promising MOFs is the zeolitic imidazolate framework (ZIF-8) crystal, an advanced functional material for small-molecule delivery, due to its high loading ability and pH-sensitive degradation. As a novel carrier, ZIF-8 nanoparticles were used in this work to control the release of an autophagy inhibitor, 3-methyladenine (3-MA), and prevent it from dissipating in a large quantity before reaching the target. The cellular uptake in HeLa cells of 3-MA encapsulated in ZIF-8 (3-MA@ZIF-8 NPs) is facilitated through the nanoparticle internalization with reference to TEM observations and the quantitative analyses of zinc by ICP-MS. The autophagy-related proteins and autophagy flux in HeLa cells treated with 3-MA@ZIF-8 NPs show that the autophagosome formation is significantly blocked, which reveals that the pH-sensitive dissociation increases the efficiency of autophagy inhibition at the equivalent concentration of 3-MA. In vivo experiments, when compared to free 3-MA, 3-MA@ZIF-8 NPs show a higher antitumor efficacy and repress the expression of autophagy-related markers, Beclin 1 and LC3. It follows that ZIF-8 is an efficient drug delivery vehicle in antitumor therapy, especially in inhibiting autophagy of cancer cells.

A zeolitic imidazolate framework (ZIF-8) with high loading capacity and pH-responsive properties, an important subclass of metal-organic frameworks (MOFs), has become a promising material for drug delivery. A multifunctional drug delivery system (DDS) was designed in this work for effective targeting delivery of chloroquine diphosphate (CQ) as an autophagy inhibitor. The ZIF-8 nanoparticles encapsulating CQ (CQ@ZIF-8 NPs) were fabricated by a simple one-pot method and were then decorated with methoxy poly(ethylene glycol)-folate (FA-PEG), a special identifier of cancer cells, to form FA-PEG/CQ@ZIF-8. The target identification of FA-PEG/CQ@ZIF-8 NPs, compared with CQ@ZIF-8 NPs, leads to an increasing number of NPs being internalized into HeLa cells, which decreases the loss of drugs and results in high cytotoxicity of CQ for cancer cells. The lower viabilities of HeLa cells (cancer cells) and higher viabilities of HEK293 cells (healthy cells) treated with FA-PEG/CQ@ZIF-8 NPs show that the special target for cancer cells results from the combinations of folic acid and folate receptors on the surface of HeLa cells. The quantitative measurements of autophagy-related proteins and the detection of autophagy flux in HeLa cells suggest that the autophagosome formation and autophagy flux are appreciably blocked after the cells are treated with FA-PEG/CQ@ZIF-8 NPs. The ZIF-8 can disintegrate only under low pH conditions, resulting in fast and full release of CQ. The pH-responsive and tumor-targeted properties of the NPs can control the drug release and enhance the efficiency of autophagy inhibition. It indicates that the FA-PEG/CQ@ZIF-8 NPs combining target identification with controlled drug release can be used as a novel model for discussing targeted cancer therapy and inhibiting the autophagy of cancer cells.

Cervical cancer is the most common malignancy of the female reproductive tract, and the poor response to prophylactic vaccines and the toxicity of high‑dose chemotherapeutic drugs have limited their clinical application. Spermidine, a natural polyamine detected in all eukaryotic organisms, exhibits functions that promote longevity in multiple model systems and may constitute a promising agent for cancer treatment. However, the potential effectiveness of spermidine in cervical cancer has not yet been fully elucidated, and the underlying molecular mechanisms remain unclear. In the present study, we aimed to assess the effects of spermidine on proliferation and apoptosis of HeLa cells (a cervical cancer cell line). Firstly, CCK‑8 and flow cytometric assays revealed that spermidine reduced the proliferation of HeLa cells in a dose‑dependent fashion by arresting the cell cycle at the S phase. Secondly, flow cytometry incorporating Annexin V‑FITC/PI‑staining revealed that spermidine promoted the apoptosis of HeLa cells, and western blot analysis revealed that spermidine activated autophagy. Finally, spermidine‑activated autophagy mediated the inhibition of cell proliferation by spermidine and spermidine‑induced apoptosis in HeLa cells. Collectively, these results revealed a novel function for spermidine in inhibiting cellular proliferation and inducing apoptosis of HeLa cells by activating autophagy, which may have important implications for the use of spermidine in cervical cancer therapy.

Epigallocatechin-3-gallatea (EGCG), a key component of tea, has been found to have anticancer activity but poor stability. To improve its antioxidative stability and widen the application of EGCG in anticancer therapy, a kind of EGCG derivative, EGCG palmitate (PEGCG), was synthesized and encapsulated in ZIF-8 nanoparticles with functionalization of folic acid (FA), which is commonly used as pH-responsive drug carrier. PEGCG encapsulated in polyethylene glycol (PEG)–FA/ZIF-8 nanoparticles (PEG–FA/PEGCG@ZIF-8 NPs) exhibits sixfold improvement of stability compared to that of free PEGCG. With target recognition between folic acid (FA) on the surface of NPs and overexpressed FA receptor (FR) in cancer cells, the NPs can be efficiently internalized into cells and present targeted effects of inhibition growth on HeLa cells (cancer cells) compared with HEK 293 cells (normal cells), consistent with the regulation of reactive oxygen species (ROS) level and the induction of autophagy. The detection of autophagy flux and the measurement of autophagy marked proteins in cells suggest that autophagy flux and the autophagosome formation are appreciably induced when the cells were treated with PEG–FA/PEGCG@ZIF-8 NPs. It indicates that pH-responsive PEG–FA/PEGCG@ZIF-8 NPs with target identification for cancer cells can be used as highly efficient drug carriers in targeting cancer chemotherapy.

embedded metal nanoparticles in nanopores is essential for catalytic investigation.In the present study, we demonstrate a general and scalable synthesis approach to PtCo nanoparticles embedded in nitrogen-doped graphene nanopores (PtCo/NPG) through direct in situ etching by platinum phthalocyanine (PtPc) and cobalt phthalocyanine (CoPc) in pristine graphene. To our knowledge, no attention has been given to the use of PtPc as precursor to alloy formation. Nitrogen-rich PtPc and CoPc supply abundant N sources, as well as in situ-formed nano pores and alloy nanoparticles generated on the graphene sheets. Nanopore edges act as the anchoring sites for PtCo nanoparticles and exert a synergetic coupling effect between nanopores and PtCo nanoparticles. The strong interactions between PtCo nanoparticles and nanopores supply a possible means to modulate the electronic properties of PtCo nanoparticles, which helps to partially inhibit Pt oxidation and dissolution during ORR. Furthermore, this unique structure may reduce the dissociation activation energy of molecular O 2 and sequentially enhance the electrocatalytic ORR activity and durability. The obtained PtCo/NPG showed superb electrocatalytic activity and stability for ORR, outperforming the state-of-the-art catalyst Pt/C.The fabrication of PtCo/NPG hybrid is demonstrated in Scheme 1 . Amounts of PtPc, CoPc, dipyridylacetylene (dpa), glucose, and graphene were mixed together and stirred in water for 12 h. CoPc and PtPc can be easily coordinated to both ends of dpa through the bond formed between the pyridine of dpa and the Co, Pt center in CoPc, PtPc, respectively, during refl ux, and then the molecules can be dispersed on the basal plane of graphene uniformly. The mixture was further coated with a thin layer of amorphous carbon via hydrothermal carbonization of glucose. The thin carbon layer can reduce the sublimation of PtPc and CoPc during pyrolysis and obviously decrease agglomeration. The obtained nanocomposites were fi nally annealed under N 2 atmosphere at 700 °C for 2 h to yield PtCo/ NPG nanohybrid. For comparison, a similar reaction procedure was conducted using only PtPc as precursor (Pt/NPG). Moreover, potassium tetrachloroplatinate (II) and cobalt nitrate were reduced on nitrogen-doped graphene (NG) and pristine graphene (G) by adding sodium borohydride to obtain PtCo-supported materials, which were denoted as PtCo/NG and PtCo/G.Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to investigate the microstructures and morphology of PtCo/NPG. As depicted in Figure 1 a and Figure S1 (Supporting Information), PtCo/NPG displays Recently, graphene has attracted considerable attention for its several advantages, such as extraordinarily large surface area and enhanced conductivity; moreover, graphene has been used to disperse metal nanoparticles and thus improve the performance of oxygen reduction reaction (ORR). [ 1 ] The distribution and morphology of metal nanoparticles in graphene can be easily controlled. However, the dist...