Recent Advances in Glucose‐Oxidase‐Based Nanocomposites for Tumor Therapy

Glucose oxidase (GOx) can react with intracellular glucose and oxygen (O₂) to produce hydrogen peroxide (H₂O₂) and gluconic acid, which can cut off the nutrition source of cancer cells and consequently inhibit their proliferation. Therefore, GOx is recognised as an ideal endogenous oxido‐reductase for cancer starvation therapy. This process can further regulate the tumor microenvironment by increasing the hypoxia and the acidity. Thus, GOx offers new possibilities for the elaborate design of multifunctional nanocomposites for tumor therapy. However, natural GOx is expensive to prepare and purify and exhibits immunogenicity, short in vivo half‐life, and systemic toxicity. Furthermore, GOx is highly prone to degrade after exposure to biological conditions. These intrinsic shortcomings will undoubtedly limit its biomedical applications. Accordingly, some nanocarriers can be used to protect GOx from the surrounding environment, thus controlling or preserving the activity. A variety of nanocarriers including hollow mesoporous silica nanoparticles, metal–organic frameworks, organic polymers, and magnetic nanoparticles are summarized for the construction of GOx‐based nanocomposites for multimodal synergistic cancer therapy. In addition, current challenges and promising developments in this area are highlighted.     

Intelligent anticancer drug delivery performances of two poly(N-isopropylacrylamide)-based magnetite nanohydrogels

This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe₃O₄ nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating–sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41?°C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37?°C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery.     

A NIR-II Fluorescent PolyBodipy Delivering Cationic Pt-NHC with Type II Immunogenic Cell Death for Combined Chemotherapy and Photodynamic Immunotherapy

Tumor immunotherapy has emerged as one of the most promising clinical techniques to treat cancer tumors. Despite its clinical application, the cancerous immunosuppressive microenvironment limits the therapeutic efficiency of the treatment. To generate a stronger immunogenic therapeutic effect, herein, a platinum complex for chemotherapy and a BODIPY photosensitizer for photodynamic therapy are encapsulated into multimodal type II immunogenic cell death (ICD) induce nanoparticles. As the platinum complex and the photosensitizer are able to induce type II ICD, an exceptionally strong immune response is observed in triple-negative breast cancer cells. While remaining stable and therefore poorly cytotoxic in the dark, the nanomaterial is found to quickly dissociate upon exposure to near-infrared light, causing a multimodal mechanism of action in cancer cells as well as multicellular tumor spheroids through combined chemotherapy, photodynamic therapy, and immunotherapy. The nanoparticles are found to nearly fully eradicate a triple-negative breast cancer tumor and therefore to strongly enhance the survival of tumor-bearing mice models using low drug and light doses.     

Assessment of the Efficacy and Clinical Utility of Different Circulating Tumor Cell (CTC) Detection Assays in Patients with Chemotherapy-Naïve Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

We herein investigated the detection frequency and clinical relevance of circulating tumor cells (CTCs) in chemotherapy-naïve stage IIIB/IV non-small cell lung cancer (NSCLC), by using the CellSearch and real-time CEACAM5mRNA assays. Blood samples from 43 patients were obtained at different time points during first-line chemotherapy. CellSearch revealed the detection of ≥1 CTCs in 41.9%, 40.9%, and 16.7% of patients at baseline, post-1st, and post-2nd treatment cycle, respectively, and of ≥5 CTCs in 11.6%, 9.1%, and 5.6%, respectively. CEACAM5mRNA+ CTCs were detected in 29.3% and 16% of patients pre- and post-treatment, respectively. The positivity concordance between the two assays was 2.2%. CTC-detection by CellSearch (≥5 CTCs: p = 0.004), CEACAM5mRNA (p = 0.010), or by any assay (p = 0.000) was associated with disease progression. Reduced survival was demonstrated for patients harboring ≥5 CTCs (progression-free survival; PFS: p = 0.000; overall survival; OS: p = 0.009), CEACAM5mRNA+ CTCs (PFS: p = 0.043; OS: p = 0.039), and CTCs by any assay (PFS: p = 0.005; OS: p = 0.006, respectively). CTC-detection by any assay independently predicted for increased risk of relapse (hazard ratio; HR: 3.496; p = 0.001) and death (HR: 2.866; p = 0.008). CellSearch-positivity either pre-, post-1st, or post-2nd cycle, was predictive for shorter PFS (p = 0.036) compared to negativity in all time points. Persistent CEACAM5mRNA-positivity pre- and post-treatment was associated with reduced PFS (p = 0.036) and OS (p = 0.026). In conclusion, CTC detection and monitoring using the CellSearch and CEACAM5mRNA assays provides valuable and complementary clinical information for chemo-naïve advanced or metastatic NSCLC.     

Conceptualization of Disease Timeline Predicts Posttreatment Distress in Breast Cancer Patients.

A sample of 69 breast cancer patients was assessed before and after cessation of treatment to determine the predictors of posttreatment distress. Patients were assessed approximately 6 weeks before completing chemotherapy treatment, 1 month after completing treatment, and 3 months after completing treatment. Results indicate that timeline beliefs are related to distress: Patients who conceptualize their cancer as a chronic or cyclic illness are more anxious, depressed, and worried about a recurrence than patients who conceptualize their cancer as an acute illness. These findings hold true even while controlling for disease stage. The way patients conceptualize their illness appears to be more influential in determining levels of posttreatment distress than objective indicators of the likelihood of recurrence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bone Marrow Dendritic Cells Derived Microvesicles for Combinational Immunochemotherapy against Tumor

Various types of cell can change the cytoskeleton and shed microvesicles (MVs) with biomimic properties as parent cells in response to stimuli. To take use of the drug package capability of MVs and the potent antigen presentation property of dendritic cells (DCs), DC‐derived antigenic MVs are constructed by priming DCs with tumor‐derived MVs and then encapsulating a chemotherapeutic drug during MVs shedding. This kind of MVs exhibit significant inhibition on melanoma tumor growth and metastasis. The MV‐encapsulated chemotherapeutics can induce direct cytotoxicity and immunogenic cell death in tumor cells. Moreover, a robust antitumor immunity is induced in both, the tumor‐draining lymph node and the tumor microenvironment as the infiltration and activation of T lymphocytes increases. This kind of MVs is further explored in a hepatic ascites model with remarkable prolonged overall survival of mice. More importantly, the MVs can extend the survival of 60% mice more than 150 d without ascites even after rechallenging the tumor twice. This study demonstrates that antigenic MVs with chemotherapeutics possess great potential in cancer immunochemotherapy.     

Polymer-Immobilized Photosensitizers for Continuous Eradication of Bacteria

The photosensitizers Rose Bengal (RB) and methylene blue (MB), when immobilized in polystyrene, were found to exhibit high antibacterial activity in a continuous regime. The photosensitizers were immobilized by dissolution in chloroform, together with polystyrene, with further evaporation of the solvent, yielding thin polymeric films. Shallow reservoirs, bottom-covered with these films, were used for constructing continuous-flow photoreactors for the eradication of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli and wastewater bacteria under illumination with visible white light using a luminescent lamp at a 1.8 mW·cm⁻² fluence rate. The bacterial concentration decreased by two to five orders of magnitude in separate reactors with either immobilized RB or MB, as well as in three reactors connected in series, which contained one of the photosensitizers. Bacterial eradication reached more than five orders of magnitude in two reactors connected in series, where the first reactor contained immobilized RB and the second contained immobilized MB.     

Enhanced Efficacy of Gefitinib in Drug-Sensitive and Drug-Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety

Attractive results have been achieved with small-molecule target-based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small-molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound ( Y5-1 ), in which a small-molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug-resistant cell lines.