Hydrogen-Bonded Organic Frameworks Based Mixed-Matrix Membranes with Low Temperature Antiviral Activity

Hydrogen-bonded organic frameworks (HOFs) are a type of porous molecular crystal consisting of multiple rigid large π-conjugated structures. They hold great potential as photosensitive antiviral materials due to their solution processability. Moreover, HOFs can easily bind to polymeric matrices, making them a flexible and green option for low-temperature antiviral materials. In this study, we fabricated a series of HOF@polymer mixed-matrix membranes (MMMs) by a solution casting technique for low temperature antiviral applications. The incorporation of HOF-101 crystals into poly vinylidene difluoride (PVDF) membranes can enhance their mechanical strength by at least 20%. The unique one-dimensional pore channels of HOF-101 enable the MMMs to have increased exposure to oxygen, providing the potential for enhanced generation of singlet oxygen (1O2). The 1O2 generated by 1 wt % HOF-101@PVDF MMMs at 263 K was observed to be more than 40% higher compared to that at 298 K. The excellent 1O2 generation efficiency allowed the MMMs to maintain their virucidal efficacy by more than 99% and 95% against vesicular stomatitis virus and herpes simplex virus type 1, respectively, at low temperatures

Impact of Autophagy Inhibition at Different Stages on Cytotoxic Effect of Autophagy Inducer in Glioblastoma Cells

Background/Aims: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a poor prognosis. Combination treatment of autophagy inducer and autophagy inhibitor may be a feasible solution to improve the therapeutic effects. However, the correlation between them is unclear. The purpose of this study was to investigate the effect of autophagy inhibition at different stages on cytotoxicity of autophagy inducers in glioblastoma cells. Methods: Autophagy inhibition at early stage was achieved by 3-methyladenine (3-MA) or Beclin 1 shRNA. Autophagy inhibition at late stage was achieved by chloroquine (CQ) or Rab7 shRNA. Cell viability was assessed by MTT assay. Autophagy was measured using transmission electron microscopy and western blot. Apoptosis was measured using western blot and flow-cytometry. Results: Inhibition of early steps of autophagy by 3-MA or Beclin 1 knockdown decreased the toxic effect of arsenic trioxide (ATO) in GBM cell lines. In contrast, blockade of autophagy flux at late stage by CQ or Rab7 knockdown enhanced the cytotoxicity of ATO, and caused accumulation of degradative autophagic vacuoles and robust apoptosis. Moreover, depletion of Beclin 1 abolished the synergistic effect of ATO and CQ by reducing autophagy and apoptosis. Combination of CQ with other autophagy inducers also induced synergistic apoptotic cell death. Conclusion: These results suggest that inhibition of late process of autophagy, not initial step, increases the cytotoxic effect of autophagy inducers via autophagy and apoptosis, which may contribute to GBM chemotherapy

Biomimetic Human Serum Albumin Nanoparticle for Efficiently Targeting Therapy to Metastatic Breast Cancers

Triple-negative breast cancers (TNBCs), devoid of hormone receptors and human epidermal growth-factor receptor-2/Neu expression, bring about poor prognosis and induce a high rate of systematic metastases. The ineffectiveness of current therapies on TNBCs could be attributed to the lack of efficient targeted therapy. Paclitaxel (PTX) is considered one of first-line chemotherapeutics for TNBC treatment but, due to its low aqueous solubility and nonspecific accumulation, results in poor antitumor efficacy. The present study is aimed at enhancing the chemotherapeutic potency of PTX by improving the stability and targeting efficiency of PTX-loaded nanoparticulate drug carriers. Here, PTX was incorporated in nontoxic and endogenous material, human serum albumin (HSA), via an innovative disulfide reduction method to construct HSA-based PTX nanoparticle (HSA-PTX NP) to not only realize redox-responsive drug release but also improve in vivo stability. Besides, W peptide was selected as a target ligand to be conjugated with HSA-PTX NP for endowing active targeting ability. The resulting Wpep-HSA-PTX NP possessed a spherical structure (118 nm), 9.87% drug-loading content, and 86.3% entrapment efficiency. An in vitro drug release test showed that PTX release from Wpep-HSA-PTX NP was of a redox-responsive manner. Furthermore, cellular uptake of Wpep-HSA-PTX NP was significantly enhanced, exhibiting the improved antiproliferation and antitube formation effects of PTX in vitro. In comparison with those commercial formulations and conventional HSA NP, Wpep-HSA-PTX NP exhibited better pharmacokinetic behaviors and tumor homing characteristics. The antitumor efficacy of Wpep-HSA-PTX NP was further confirmed by the strong pro-apoptotic effect and reduced tumor burden. In a word, this evidence highlighted the proof of concept for Wpep-HSA NP as a promising conqueror to the ineffectiveness of TNBC therapy

T7 Peptide-Functionalized PEG-PLGA Micelles Loaded with Carmustine for Targeting Therapy of Glioma

Glioma is regarded as the deadliest and most common brain tumor because of the extremely difficult surgical excision ascribed from its invasive nature. In addition, the natural blood-brain barrier (BBB) greatly restricts the therapeutics’ penetration into the central nervous system. Carmustine (BCNU) is a widely used antiglioma drug in clinical applications. However, its serious complications prevent it from being applied in a clinical setting to some extent. Thus, it is urgent to explore novel BCNU delivery systems specially designed for glioma. Development of polymeric nanoparticles offers a favorable alternative to serve this purpose. Particularly, use of poly­(lactic-<i>co</i>-glycolic acid) (PLGA) has been shown to be advantageous for its favorable biodegradability and biocompatibility, which ensure safe therapies. In this study, T7 peptide-conjugated, BCNU-loaded micelles were constructed successfully via the emulsion-solvent evaporation method. The micelles were characterized by transmission electron microscopy and dynamic light scattering in detail, and the capacity of BBB crossing was studied. The in vivo detecting results of the targeting effect using the BODIPY probe evidenced that T7-modified micelles showed a more pronounced accumulation and accumulated in the tumor more efficiently than in the unconjugated probe. Meanwhile, the targeting group exhibited the best curative effect accompanied with the lowest loss in body weight, the smallest tumor size, and an obviously prolonged survival time among the groups. In the near future, we believe the targeted delivery system specially designed for BCNU is expected to provide sufficient evidence to proceed to clinical trials