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• Thermosensitive hydrogel prepared from TPGS for the first time. • Locoregional therapy of cancer using hydrophobic drug loaded hydrogel. • Therapeutic TPGS hydrogel and synergistic effect between drug and the hydrogel carrier. D-ɑ-tocopheryl poly(ethylene glycol)1000 succinate (TPGS) has been extensively applied in drug delivery systems for its amphiphilic property and inherent bioactivity. But TPGS has not always been utilized solely for the unstability of TPGS micelle. Inspired by the hydrogels made from other amphiphilic molecules, thermosensitive TPGS hydrogels were firstly discovered and developed in the presence of specific anions, which self-assembled from the aggregation of TPGS micelles stimulated by heating and salting-out effect. Subsequently, hydrophobic doxorubicin (DOX) loaded TPGS micelles were likewise prepared and converted into DOX loaded hydrogel with the help of β-Glycerol phosphate disodium (β-GP). It was found that the amount of TPGS and β-GP in the solution considerably affected the gelation time and critical temperature. One of the formulations containing 4 wt% TPGS and 15 wt% β-GP was selected due to its appropriate gelation time and temperature for subcutaneously injection. Pristine and drug-loaded TPGS hydrogels were explored for their potential values in clinic applications. Derived from the bioactivity of TPGS, the pristine TPGS hydrogel exhibited a certain tumor inhibiting efficiency comparable to the DOX-containing formulations. And the efficiency of DOX-loaded TPGS hydrogels were dosage-dependent and superior to systemically administrated free DOX, which demonstrated a synergistic effect between DOX and TPGS hydrogel. In short, this study developed a multifunctional injectable hydrogel and provided a new synergetic strategy for tumor therapy. [ABSTRACT FROM AUTHOR]

• Oxaliplatin precursor (oxa-pre) up-regulated CD47 expression in colon cancer. • HCLO NPs restrained the up-regulation effect of oxa-pre on CD47. • HCLO NPs induced potent antitumor immunity. • HCLO NPs achieved targeted co-delivery of oxa-pre and CpG. Chemo-immunotherapy has the superiority of remedying malignant and metastatic tumors, and acquiring better therapeutic effect as well as prognosis than monotherapy. Herein, we report a kind of pH-responsive core-shell nanoparticles to achieve the co-delivery of oxaliplatin intermediate (oxa im) (HCLO NPs) and cytosine-guanine containing oligodeoxynucleotides (CpG) for cancer treatment. The nanoparticles comprise the core of lipid-coated calcium carbonate and the outer layer of hyaluronic acid (HA), providing itself with pH-sensitivity and great biocompatibility. When intratumorally injected, oxa im induces in situ antigen production through immunogenic cell death (ICD) while CpG enhances antigen presentation and facilitates the generation of cytotoxic T lymphocytes (CTLs). In vitro , the HCLO NPs enhanced the toxicity of oxa im to CT26 cells and up-regulated the expression of calreticulin (CRT, "eat me" signal). What's more, oxaliplatin precursor (oxa pre) directly upregulated CD47 ("don't eat me" signal) expression in CT26 cells, while being encapsulated into NPs attenuated this upregulation. In vivo , HCLO NPs elicited prominent anti-tumor immunity and abscopal effect, meanwhile significantly increased the infiltration of CD8+ T cells in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

• Cisplatin treatment caused ROS elevation and thereby HIF-1 expression. • HIF-1-regulated pathways were responsible for acquired cisplatin resistance. • Reducing ROS level to prevent HIF-1 activation could combat drug-resistance. • Nano-Se was demonstrated to scavenge ROS and thereby reverse drug-resistance. • Cisplatin-doped Nano-Se was prepared in a facile one-pot synthesis method. The clinical efficacy of cisplatin (DDP) treatment is largely limited by cisplatin resistance, which is related to the activation of hypoxia-inducible factor 1 (HIF-1). The HIF-1 activation can be induced by low oxygen availability as well as chemotherapeutics in a reactive oxygen species (ROS) dependent manner. Here, instead of the traditional ROS elevation strategy, we designed a chitosan-coated selenium/DDP (CSP) nanoparticle to deplete ROS for circumventing acquired cisplatin resistance. The antioxidative selenium nanoparticles were demonstrated to eliminate cisplatin-induced ROS, and further prevent HIF-1 activation accompanied with cisplatin treatment. A series of cisplatin resistance-associated proteins including glutamate-cysteine ligase modifier subunit (GCLM) and multidrug resistance-associated proteins (MRPs) expression were downregulated in a HIF-1α-dependent manner. And in vitro and in vivo experiments showed that CSP nanoparticles exhibited enhanced antitumor efficacy to cisplatin-resistant A549/DDP lung cancer cell lines and xenografts. These results proved that the side effects of treatment-induced ROS in HIF-1 activation and cisplatin-resistance could be significantly reversed by a selenium nanovehicle, which may possess broader applications in ROS-mediated resistance or other ROS-involved diseases. [ABSTRACT FROM AUTHOR]