Angiopep-2-Modified Carboxymethyl Chitosan-Based pH/Reduction Dual-Stimuli-Responsive Nanogels for Enhanced Targeting Glioblastoma.

Glioblastoma (GBM) is a fatal brain tumor with poor prognosis. Blood-brain barrier (BBB) prevents the effective delivery of chemotherapeutic agents to GBM. Herein, we developed a pH/reduction-sensitive carboxymethyl chitosan nanogel (CMCSN) modified by targeting peptide angiopep-2 (ANG) and loaded with doxorubicin (DOX). The multifunctional nanogel (DOX-ANG-CMCSN) exhibited good pH and reduction sensitivity, ideal stability, and biocompatibility. Its hydrodynamic diameter was 190 nm, drug loading was 12.7%, and the cumulative release rate of 24 h was 82.3% under the simulated tumor microenvironment. More importantly, the modification of ANG significantly enhanced BBB penetration and tumor targeting ability both in vivo and in vitro. DOX-ANG-CMCSN achieved 2-3-fold higher uptake and an enhanced antitumor activity compared with nontargeted DOX-CMCSN. Therefore, the targeted nanogels with the pH/reduction dual-stimuli response may provide a promising platform for GBM-targeted chemotherapy.

Mussel-inspired nanocomposite hydrogel based on alginate and antimicrobial peptide for infected wound repair.

Timely hemostasis, antibacterial activity, and good adhesion are essential for wound healing. Here, we report about a novel nanocomposite hydrogel with hemostatic, antibacterial, and adhesive properties constructed with a mussel-inspired strategy. Oxidized alginic acid, dopamine, and antimicrobial peptide ε-polylysine were used to prepare a nanocomposite (ODP), and then further cross-linked with acrylamide to fabricate a nanocomposite hydrogel (ODPA). ODPA hydrogel can adhere to the surface of bleeding organs and arrest bleeding within 30 s. It can also be stretched to 12 times its original length and withstand a compression strain of 40 %, and shows effective inhibition on gram-positive and gram-negative bacteria. Compared with commercial alginate sponge, ODPA hydrogel can accelerate the healing of infected full-thickness wound by reducing inflammation, promoting angiogenesis, and collagen deposition. Therefore, the nanocomposite hydrogel is expected to be a multifunctional dressing for promoting healing of infected wounds.

Upregulation of MHC-I and downregulation of PD-L1 expression by doxorubicin and deferasirox codelivered liposomal nanoparticles for chemoimmunotherapy of melanoma.

Tumor immunotherapy is a promising strategy to activate the immune system and eliminate tumors. Major histocompatibility complex I (MHC-I) is usually applied to potentiate antigen presentation, but it is associated with upregulation of programmed death ligand 1 (PD-L1) expression, which is unfavorable for activation of immune responses. Moreover, poor permeability of various therapeutic antibodies results in the limited immune response rates of most patients. It is necessary to develop combined small molecule drug delivery systems for simultaneous upregulation of MHC-I expression and downregulation of PD-L1 expression, promoting effective tumor treatment. A moderate dose of doxorubicin hydrochloride (DOX) can induce upregulation of MHC-I expression, while deferasirox (DFX) can inhibit the PI3K-Akt pathway, which potentially downregulates PD-L1 expression. In the present study, we designed a pH-sensitive liposome to incorporate DOX in the hydrophilic cavity and embed DFX in the hydrophobic shell, forming a dual delivery system (DOX-DFXL). In a B16F10 melanoma-bearing mouse model, DOX and DFX were released in acidic tumor microenvironment, which further lead to enhanced antigen presentation and infiltration of T cells into tumor tissues as a result of tumor remission. This codelivery system holds great potential for clinical applications of tumor immunotherapy.

Functional 2D Iron-Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor.

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.

Iota carrageenan gold-silver NPs photothermal hydrogel for tumor postsurgical anti-recurrence and wound healing.

Tumor surgery is often accompanied by tumor residue, tissue defects, bleeding, and bacterial infection, which can easily cause tumor recurrence, low survival rates, and delay wound healing. In this study, a multifunctional hydrogel (CA-AuAgNPs-Gel) was developed to prevent tumor recurrence and promote wound healing after tumor surgery in the absence of chemotherapeutic drugs and antibiotics. CA-AuAgNPs-Gel was prepared using iota carrageenan (CA)-capped gold­silver nanoparticles (CA-AuAgNPs) and poloxamer 407 (F127), which exhibited good biocompatibility, injectability, and near-infrared (NIR) photothermal responsiveness. CA-AuAgNPs-Gel inhibited the growth of 4T1 breast cancer in situ and the recurrence of surgically resected B16F10 melanoma. It also effectively stopped bleeding and promoted tumor postsurgical wound healing in vivo. Importantly, CA-AuAgNPs-Gel induced tumor apoptosis via photothermal-induced hyperthermia and immunogenic cell death (ICD) under NIR laser radiation. Collectively, this hydrogel shows significant clinical application prospects for inhibiting tumor recurrence and promoting wound healing for postsurgical tumor treatment.

Immunomodulation of Tumor Microenvironment by Arginine-Loaded Iron Oxide Nanoparticles for Gaseous Immunotherapy.

Tumor-associated macrophages (TAMs) of M2 phenotype have mediated the immunosuppression in a tumor microenvironment, facilitating the escape of tumor cells from immunosurveillance. Reprograming the immunosuppressive M2 TAMs to immunostimulatory M1 phenotype can activate the antitumor immune responses for cancer immunotherapy. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were employed to reprogram M2 TAMs toward M1 TAMs, aiming to release proinflammatory cytokines and recruit T cells to kill tumor cells. After loaded with l-arginine (l-Arg) and sealed with poly(acrylic acid) (PAA), hollow Fe3O4 NPs were fabricated into LPFe3O4 NPs, which could release l-Arg based on pH-responsive PAA and produce nitric oxide (NO) with the help of nitric oxide synthase (iNOS) overexpressed by M1 TAMs, as a result of additional tumor elimination for gas therapy. In vitro and in vivo studies demonstrate that LPFe3O4 NPs could effectively reprogram M2 to M1 macrophages, activating T cells, releasing TNF-α, and producing high levels of NO, leading to synergistic tumor therapy.

Photo-driven self-powered biosensor for ultrasensitive microRNA detection via DNA conformation-controlled co-sensitization behavior.

We successfully developed a photoelectrochemical enzymatic fuel cell (PEFC)-based self-powered biosensing platform for microRNA detection via DNA conformation change-controlled co-sensitization behavior, which could offer ultrasensitive detection of microRNA down to 0.05 fM and realize microRNA determination in human serum.

[Uvulopalatopharyngoplasty and hyoid suspension for obstructive sleep apnea hyponea syndrome].

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of uvulopalatopharyngoplasty (UPPP) with hyoid suspension for patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Thirty-eight OSAHS patients underwent UPPP with hyoid suspension. Review the sleep monitoring after 6 months and 1 year and compare the AHI, LSaO 2 and ESS score. RESULT: The average AHI decreased, and blood oxygen saturation increased significantly afer operation. CONCLUSION: UPPP with hyoid suspension is an available and relatively safe surgical approach in OSAHS patients.