An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Bovine serum albumin-based and dual-responsive targeted hollow mesoporous silica nanoparticles for breast cancer therapy.

Combination therapy is an effective way to alleviate the shortcoming of monotherapy and enhances therapeutic efficacy. Herein, a distinctive hollow mesoporous silica nanoparticle (HMSNs) encapsulated with folic acid-modified bovine serum albumin (BSA-FA), denoted as HBF, was engineered for tumor targeting and dual-responsive release of loaded-therapeutic agents MD (methylene blue (MB) and doxorubicin (DOX)). The BSA molecule as a ''gatekeeper'' prevents premature drug leakage and actively unloads the cargos through BSA detachment in response to intracellular glutathione (GSH). Folic acid (FA) promotes the specific intracellular delivery of the drug to folate receptor (FR)-expressing cancer cells to improve the efficacy of chemo-photodynamic therapy (PDT). In vitro drug release profiles showed that the drug carrier could achieve pH/redox-responsive drug release from MD@HBF owing to the cleavage of the imine bonds between HMSNs-CHO and BSA-FA and BSA intramolecular disulfide bond. Additionally, a series of biological evaluations, such as cell uptake experiments, toxicity experiments, and in vivo therapeutic assays indicated that MD@HBF possesses the features of accurately targeting FR-expressing 4T1 cells to induce cells apoptosis in vitro, exhibits outstanding tumor cell synergistic killing efficiency of chemo-photodynamic therapy (combination index CI = 0.325), and inhibits tumors growth. These results demonstrated that the strategy of combining HMSNs with stimuli-responsive biodegradable protein molecules could provide a new potential direction toward the ''on-demand'' drug release for precision chemo-photodynamic therapy in cancer treatment.

Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials.

Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O2 by a photosensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.

Antiviral potential of natural products from marine microbes.

Humans have been suffered from viral infections over the centuries, such as influenza, HSV, and HIV, which have killed millions of people worldwide. However, the availability of effective treatments for infectious diseases remains limited until now, as most of the viral pathogens resisted to many medical treatments. Marine microbes are currently one of the most copious sources of pharmacologically active natural products, which have constantly provided promising antivirus agents. To date, a large number of marine microbial secondary metabolites with antiviral activities have been widely reported. In this review, we have summarized the potential antivirus compounds from marine microorganisms over the last decade. In addition, the structures, bioactivities, and origins of these compounds were discussed as well.

A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000-2018.

Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more attention due to their unique mechanism of anti-inflammatory action, and have considered a hotspot for anti-inflammatory drug development. Marine-derived fungi are promising sources of structurally unprecedented bioactive natural products. So far, a plethora of new secondary metabolites with anti-inflammatory activities from marine-derived fungi had been widely reported. This review covers 133 fungal metabolites described in the period of 2000 to 2018, including the structures and origins of these secondary metabolites.

Separation of five diketopiperazines from the marine fungus Alternaria alternate HK-25 by high-speed counter-current chromatography.

High-speed counter-current chromatography was applied to the separation of five diketoperazines from the marine Alternaria alternate HK-25 for the first time using one-step elution method with a pair of two-phase solvent systems composed of petroleum ether/ethyl acetate/methanol/water (5.5:11:5:7, v/v). Where 151.6 mg of crude sample yielded five diketoperazines, 12,13-dihydroxy-fumitremorgin C (1), gliotoxin (2), demethoxyfum itremorgin C (3), bisdethiobis(methylthio)gliotoxin (4), fumitremorgin C (5), and the purities of all compounds were above 94% as determined by high-performance liquid chromatography. The structures of these compounds were identified by 1 H and 13 C NMR spectroscopy. These results showed that high-speed counter-current chromatography can provide a feasible way for highly effective preparation of marine natural products, which ensured the supple of numerous samples for drug development.

Isolation and Purification of a Neuroprotective Phlorotannin from the Marine Algae Ecklonia maxima by Size Exclusion and High-Speed Counter-Current Chromatography.

Phlorotannins are polyphenolic metabolites of marine brown algae that have been shown to possess health-beneficial biological activities. An efficient approach using a combination of high-speed counter-current chromatography (HSCCC) and size exclusion chromatography with a Sephadex LH-20 has been successfully developed for the isolation and purification of a neuroprotective phlorotannin, eckmaxol, from leaves of the marine brown algae, Ecklonia maxima. The phlorotannin of interest, eckmaxol, was isolated with purity >95% by HSCCC using an optimized solvent system composed of n-hexane-ethyl acetate-methanol-water (2:8:3:7, v/v/v/v) after Sephadex LH-20 size exclusion chromatography. This compound was successfully purified in the quantity of 5.2 mg from 0.3 kg of the E. maxima crude organic extract. The structure of eckmaxol was identified and assigned by NMR spectroscopic and mass spectrometric analyses. The purification method developed for eckmaxol will facilitate the further investigation and development of this neuroprotective agent as a drug lead or pharmacological probe. Furthermore, it is suggested that the combination of HSCCC and size exclusion chromatography could be more widely applied for the isolation and purification of phlorotannins from marine algae.