RESUMEN
Herein, a multifunctional nanohybrid (PL@HPFTM nanoparticles) was fabricated to perform the integration of chemodynamic therapy, photothermal therapy, and biological therapy over the long term at a designed location for continuous antibacterial applications. The PL@HPFTM nanoparticles consisted of a polydopamine/hemoglobin/Fe2+ nanocomplex with comodification of tetrazole/alkene groups on the surface as well as coloading of antimicrobial peptides and luminol in the core. During therapy, the PL@HPFTM nanoparticles would selectively cross-link to surrounding bacteria via tetrazole/alkene cycloaddition under chemiluminescence produced by the reaction between luminol and overexpressed H2O2 at the infected area. The resulting PL@HPFTM network not only significantly damaged bacteria by Fe2+-catalyzed ROS production, effective photothermal conversion, and sustained release of antimicrobial peptides but dramatically enhanced the retention time of these therapeutic agents for prolonged antibacterial therapy. Both in vitro and in vivo results have shown that our PL@HPFTM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.
Asunto(s)
Antibacterianos , Nanopartículas , Antibacterianos/farmacología , Antibacterianos/química , Animales , Nanopartículas/química , Ratones , Escherichia coli/efectos de los fármacos , Polímeros/química , Indoles/química , Indoles/farmacología , Terapia Fototérmica , Humanos , Staphylococcus aureus/efectos de los fármacos , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacologíaRESUMEN
Although immunotherapy has revolutionized oncotherapy, only ≈15% of head and neck squamous cell carcinoma (HNSCC) patients benefit from the current therapies. An immunosuppressive tumor microenvironment (TME) and dysregulation of the polycomb ring finger oncogene BMI1 are potential reasons for the failure. Herein, to promote immunotherapeutic efficacy against HNSCC, an injectable nanocomposite hydrogel is developed with a polymer framework (PLGA-PEG-PLGA) that is loaded with both imiquimod encapsulated CaCO3 nanoparticles (RC) and cancer cell membrane (CCM)-coated mesoporous silica nanoparticles containing a peptide-based proteolysis-targeting chimeras (PROTAC) for BMI1 and paclitaxel (PepM@PacC). Upon injection, this nanocomposite hydrogel undergoes in situ gelation, after which it degrades in the TME over time, releasing RC and PepM@PacC nanoparticles to respectively perform immunotherapy and chemotherapy. Specifically, the RC particles selectively manipulate tumor-associated macrophages and dendritic cells to activate a T-cell immune response, while CCM-mediated homologous targeting and endocytosis delivers the PepM@PacC particles into cancer cells, where endogenous glutathione promotes disulfide bond cleavage to release the PROTAC peptide for BMI1 degradation and frees the paclitaxel from the particle pores to elicit apoptosis meanwhile enhance immunotherapy. Thus, the nanocomposite hydrogel, which is designed to exploit multiple known vulnerabilities of HNSCC, succeeds in suppressing both growth and metastasis of HNSCC.
Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Nanogeles , Proteolisis , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Microambiente TumoralRESUMEN
It is still a big challenge to obtain hydrophobic thermoplastic starch with outstanding mechanical performance due to the inevitable usage of typical hydrophilic plasticizers like glycerol during processing. Herein, we report a novel hydrophobic thermoplastic starch using a supramolecularly induced thermoplasticization technique. To achieve this aim, a functional sucrose-based ionic liquid crystal (ILC) including numerous chloride atoms has been firstly synthesized, and the obtained ILC molecules are then used as supramolecular inducers to thermoplasticize corn starch granules. Thermoplasticity and hydrophobicity of the prepared supramolecularly induced thermoplastic starch (STPS) with different ILC contents have been extensively investigated. Mechanism of the supramolecularly induced thermoplasticization has been investigated using molecular simulation as well. The prepared STPS with the maximum tensile strength of 8.4 MPa and water contact angle of about 117° show large potential applications in green and sustainable packaging materials.