Autophagy is a conservative eukaryotic pathway which plays a crucial role in maintaining cellular homeostasis, and dysfunction of autophagy is usually associated with pathological conditions. Recently, emerging reports have stressed that various types of nanomaterials and therapeutic approaches interfere with cellular autophagy process, which has brought up concerns to their future biomedical applications. Here, we present a study elaborating the relationships between autophagy and iron oxide nanoparticle (IONP)-mediated photothermal therapy in cancer treatment. Our results reveal that IONP photothermal effect could lead to autophagy induction in cancerous MCF-7 cells in a laser dose-dependent manner, and the inhibition of autophagy would enhance the photothermal cell killing by increasing cell apoptosis. In an MCF-7 xenograft model, cotreatment of autophagy inhibitor and IONP under laser exposure could promote the tumor inhibition rate from 43.26 to 68.56%, and the tumor immunohistochemistry assay of microtubule-associated protein 1-light chain 3 (LC3) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling also demonstrate augmentation in both autophagosomes accumulation and apoptosis in vivo. This work helps us to better understand the regulation of autophagy during IONP-mediated photothermal therapy and provides us with a potential combination therapeutic approach of autophagy modulators and photothermal agents.

Objectives: This study aimed to explore the morphology, loadability, and releasing profiles of CalliSpheres microspheres in delivering oxaliplatin. Methods: Varied amount (20, 40, 60, and 80 mg oxaliplatin) and concentration (1.25, 2.5, 5.0 mg/mL oxaliplatin) of oxaliplatin were mixed with CalliSpheres microspheres with 3 sizes (50-150 μm, 100-300 μm, and 300-500 μm) to measure the loadability. Of all, 20 mg oxaliplatin-loaded CalliSpheres microspheres with 3 sizes was prepared to measure the releasing profiles, meanwhile, fetal bovine serum was added to determine the effect of serum on oxaliplatin releasing. The morphology and size distribution of CalliSpheres microspheres with 3 sizes before and after 20 mg oxaliplatin loading were detected. Results: Oxaliplatin amount was negatively correlated with loading efficiency with highest loadability in 20 mg oxaliplatin group (maximum 40% in 50-100 µm CalliSpheres microspheres, 52% in 100-300 µm CalliSpheres microspheres, and 52% in 300-500 µm CalliSpheres microspheres), while oxaliplatin concentration was positively associated with loading efficiency. Similar drug-releasing profiles were observed among oxaliplatin-loaded CalliSpheres microspheres with 3 sizes, and a rapid drug release was discovered in CalliSpheres microspheres with 3 sizes as well. We also found that fetal bovine serum did not affect the drug-releasing profiles of oxaliplatin-loaded CalliSpheres microspheres. In addition, CalliSpheres microspheres was modified a little to ellipse shape and less smooth after oxaliplatin loading, and it was enlarged to some extent. Conclusion: This study discloses drug loadability, releasing profiles, and morphology change of CalliSpheres microspheres for delivering oxaliplatin, which provides potential evidences for application of oxaliplatin-loaded drug-eluting beads in clinical practice.

Cancer chemotherapy effect has been largely limited by cell autophagy and little drug accumulation at the action sites. Herein, we designed an intelligent strategy involving paclitaxel (PTX) polymer micelles in response to biological functions of ambroxol (Ax). The amphiphilic polymers polyethyleneglycol-polylactic acid (PEG-PLA) and Pluronic P105 were selected as nanocarriers to encapsulate PTX to form into lung affinity PEG-PLA /P105/PTX micelles. Ax which can up-regulate the secretion of pulmonary surfactant (PS) and inhibit autophagy was hired to change the microenvironment of the lung, thereby promoting the lung accumulation and increasing cell-killing sensitivity of the micelles. Methods: The physical and chemical properties of the micelles were characterized including size, morphology, critical micellar concentration (CMC) and in vitro drug release behavior. The therapeutic effects of the combination regimen were characterized both in vitro and in vivo including study on Ax in promoting the secretion of pulmonary surfactant, in vitro cytotoxicity, cellular uptake, Western blotting, in vivo biodistribution, in vivo pharmacokinetics and in vivo antitumor efficacy. Results: The PEG-PLA/P105/PTX micelles showed a particle size of 16.7 ± 0.5 nm, a nearly round shape, small CMC and sustained drug release property. Moreover, the in vitro results indicated that Ax could increase PS and LC3 protein secretion and enhance the cytotoxicity of PEG-PLA/P105/PTX micelles toward A549 cells. The in vivo results indicated that the combination therapeutic regimen could promote the micelles to distribute in lung and enhance the therapeutic effect on lung cancer. Conclusion: This multifunctional approach of modulating the tumor microenvironment to enhance drug transportation and cell-killing sensitivity in the action sites might offer a new avenue for effective lung cancer treatment.

We have constructed a novel biomimetic Pluronic-lipid nanovesicle hybrid that mimics leukocytes, to target breast cancer and suppress metastasis.