A pH-responsive polymer-coated CaO2as oxygen-generating nanoparticlein situfor enhanced chemo-photodynamic synergistic therapy against tumors.

Photodynamic therapy (PDT) has emerged as an efficient strategy for tumor treatment. However, Insufficient amounts of inherent hypoxia and intrinsic hydrogen peroxide (H2O2) in the tumor microenvironment severely constrained PDT, as oxygen is the critical substrate for photosensitivity reaction. Here, a pH-responsive H2O2and O2self-supplying hybrid nanoparticle was designed. Through, the calcium peroxide (CaO2) as carriers loading a chemotherapeutic drug a photosensitizer 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and doxorubicin (DOX), was covered with polyacrylic acid (PAA) to build up a feature material DOX-TAPP-CaO2@OA@PAA (denoted as DTCOP) through the reverse microemulsion method. In the acidic tumor microenvironment conditions exposing the water-sensitive CaO2nanocore to generate hydrogen peroxide (H2O2) and O2, the self-supplied O2alleviates hypoxia to enhance the PDT, and releasing DOX and TAPP. Synthetic characterization shows that the succeeded synthesized Nanocarriers could effectively carry DOX and TAPP to the tumor site and release O2at the low pH of TME. And the experimental results demonstrated that this interpose exogenous oxygen strategy is efficient at inhibition of tumor growth bothin vitroandin vivo. The nanocomposite exhibits excellent biocompatibility and the ability to inhibit tumor growth and has significant potential for the treatment of hypoxic tumors.

Gold nanorod-loaded thermosensitive liposomes facilitate the targeted release of ruthenium(II) polypyridyl complexes with anti-tumor activity.

Ruthenium(II) polypyridyl complexes (Ru) show high anti-tumor activity, but their poor solubility and low biocompatibility impede their use in anti-tumor therapy. Here,we circumvented the problem of low solubility by encapsulating the Ru in thermosensitive liposomes (LTSLs) and used gold nanorods (Au NRs) modified on the surface of the liposomes to permit the precise release of Ru at the tumor site. A facile and simple method was developed to synthesize Ru-loaded Au NR-decorated LTSL (Au@LTSL-Ru NPs). The loaded Au NRs improved the anti-tumor effect of Ru and enhanced the photothermal therapeutic properties of the nanosystem. A characterization experiment indicated that the average particle size of Au@LTSL-Ru was approximately 300 nm and that the Au NRs were successfully modified on the surface of LTSL. In thein vitroanti-tumor test, Au@LTSL-Ru and NIR significantly inhibited the proliferation of SGC-7901 cells. The IC50value of Au@LTSL-Ru + NIR was 7.1 ± 1.2µM (13µg ml-1), and the inhibition rate was greater than 90% when the concentration reached 30µg ml-1.In vivostudies revealed that Au@LTSL-Ru and NIR had a significant inhibitory effect on subcutaneous tumor tissues derived from SGC-7901 cells. Analysis of histopathology and immunocytotoxicity indicated that Au@LTSL-Ru has fewer side effects and high biocompatibility. Our results confirm that Au@LTSL-Ru can effectively inhibit tumor growth and aid the development of Ru for use in the thermal response in anti-tumor activity research.

Pluronic-Based Nanoparticles for Delivery of Doxorubicin to the Tumor Microenvironment by Binding to Macrophages.

The active targeting drug delivery system based on special types of endogenous cells such as macrophages has emerged as a promising strategy for tumor therapy, owing to its tumor homing property and biocompatibility. In this work, the active tumor-targeting drug delivery system carrying doxorubicin-loaded nanoparticles (DOX@MPF127-MCP-1, DMPM) on macrophage (RAW264.7) surfaces via the mediation of interaction with the CCR2/MCP-1 axis was exploited. Initially, the amphiphilic block copolymer Pluronic F127 (PF127) was carboxylated to MPF127 at the hydroxyl terminus. Subsequently, MPF127 was modified with MCP-1 peptide to prepare MPF127-MCP-1 (MPM). The DOX was wrapped in MPM to form DMPM nanomicelles (approximately 100 nm) during the self-assembly process of MPM. The DMPM spontaneously bound to macrophages (RAW264.7), which resulted in the construction of an actively targeting delivery system (macrophage-DMPM, MA-DMPM) in vitro and in vivo. The DOX in MA-DMPM was released in the acidic tumor microenvironment (TME) in a pH-responsive manner to increase DOX accumulation and enhance the tumor treatment effect. The ratio of MA-DMPM homing reached 220% in vitro compared with the control group, indicating that the MA-DMPM was excellently capable of tumor-targeting delivery. In in vivo experiments, nonsmall cell lung cancer cell (NCI-H1299) tumor models were established. The results of the fluorescence imaging system (IVIS) showed that MA-DMPM demonstrated tremendous tumor-targeting ability in vivo. The antitumor effects of MA-DMPM in vivo indicated that the proportion of tumor cell apoptosis in the DMPM-treated group was 63.33%. The findings of the tumor-bearing mouse experiment proved that MA-DMPM significantly suppressed tumor cell growth, which confirmed its immense potential and promising applications in tumor therapy.

Polydopamine Nanocarriers with Cascade-Activated Nitric Oxide Release Combined Photothermal Activity for the Therapy of Drug-Resistant Bacterial Infections.

Antibiotic abuse leads to increased bacterial resistance, and the surviving planktonic bacteria aggregate and secrete extracellular polymers to form biofilms. Conventional antibacterial agents find it difficult to penetrate the biofilm, remove the bacteria wrapped in it, and produce an excellent therapeutic effect. In this study, a dual pH- and NIR-responsive nanocomposite (A-Ca@PDA) was developed to remove drug-resistant bacteria through a cascade of catalytic nitric oxide (NO) release and photothermal clearance. NO can melt in the outer package of the biofilm, facilitating the nanocomposites to have better permeability. Thermal therapy further inhibits the growth of planktonic bacteria. The locally generated high temperature and the burst release of NO together aggravate the biofilm collapse and bacterial death after NIR irradiation. The nanocomposites achieved a remarkable photothermal conversion efficiency of 47.5%, thereby exhibiting significant advancements in energy conversion. The nanocomposites exhibited remarkable efficacy in inhibiting multidrug-resistant (MDR) Escherichia coli and MDR Staphylococcus aureus, thus achieving an inhibition rate of >90%. Moreover, these nanocomposites significantly improved the wound-healing process in the MDR S. aureus-infected mice. Thus, this novel nanocomposite offers a novel strategy to combat drug-resistant bacterial infections.