Nanoplatforms used for the loading of anticancer drugs constitute a promising approach to cancer treatment and reducing the side effects of these drugs. Among the cutting-edge systems used in this area are magnetic nanocomposites (MNCs) and nanocapsules (NCs). MNCs are considered to constitute a smart tool for magnetic-field-guided targeted drug delivery, magnetic resonance imaging, and hyperthermia therapy. Nanocapsules offer great potential due to their ability to control drug-loading capacity, their release efficiency, their stability, and the ease with which their surfaces can be modified. This study proposes a method for the development of nylon-6-coated MNCs and nylon-6 polymeric membrane NCs. A biocompatible nylon-6 polymer was first used for NC synthesis. Oleic-acid-modified and non-modified Fe3O4 nanoparticles were synthesized for the production of nylon-coated MNCs. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and ζ-potential measurements were used to perform size, morphology, and charge analyses. The above-mentioned two types of MNCs were considered templates for the manufacture of nylon nanocapsules, leading to NCs with different charges and structures. The developed oleic-acid-coated nylon-6 MNCs and NCs showed excellent loading values of the chemotherapy drug doxorubicin (DOX) of up to 732 and 943 µg/mg (DOX/MNC or NC), respectively. On the contrary, the capacity of the nano-construction that was not modified with oleic acid did not exceed 140 µg/mg. The DOX-loaded nanosystems displayed pH-sensitive drug release properties, for which the highest efficiency was observed at an acidic pH. The series of DOX-loaded MNCs and NCs inhibited A549 and HEK 293FT cell lines, with the lowest IC50 value of 0.31 µM observed for the nanocapsules, which is a 1.5-fold lower concentration than the free DOX. Therefore, the presented nanoscale systems offer great potential for cancer treatment.
There is emerging evidence that immunogenic chemotherapy is not only cytotoxic toward tumor cells but also ameliorates the immunosuppressive tumor microenvironment by inducing immunogenic cell death (ICD) to achieve long-lasting antitumor efficacy. However, comprehensive analysis of ICD inducers is lacking in lung cancer. We investigated the ability of five chemotherapeutic agents to trigger ICD. And further study of how gemcitabine (GEM) activates antitumor immunity and synergistic enhancement of antitumor immunochemotherapy. Herein, we observed that GEM induced characteristics of ICD. Moreover, we demonstrated that celecoxib could enhance ICD by attenuation of indoleamine 2,3-dioxygenase 1 (IDO-1) expression and augmentation of ROS-based endoplasmic reticulum stress. In the present study, we found the combination of GEM, celecoxib and anti-PD-1 monoclonal antibody (aPD-1) exhibited potent antitumor activity and long-term antitumor efficacy in immunocompetent mice by synergistic anti-tumor activity and recruitment of tumor infiltrating lymphocytes. These results support a combination of GEM, celecoxib and aPD-1 as a potential treatment regimen for patients with lung cancer.
Stage III non-small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this
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