RESUMO
Developing new strategies to alleviate tumor hypoxia and enhance the therapeutic efficacy towards solid tumors is of great significance to tumor therapy. Herein, to overcome tumor hypoxia, specifically designed aza-BODIPY photosensitizer is co-loaded with anti-cancer drug (doxorubicin, DOX) onto the hydrangea-structured MnO2 nanoparticles, and a tumor microenvironment (TME) responsive degradable nanoplatform (MDSP NP) is established. MDSP NPs (â¼54â¯nm), with near infrared absorption (â¼853â¯nm), can be rapidly dissociated to generate oxygen in response to TME, whereby improving tumor hypoxia, in favor of effective drugs release and enhanced chemo/photodynamic therapy. Revealed by in vivo fluorescence and photoaccoustic imaging, MDSP NPs are preferential accumulated at tumor site. Confirmed by photothermal imaging, MDSP NPs can induce hyperthermia to relieve hypoxia, promote the uptake of therapeutic nanoparticles, and further reduce the resistance and improve the therapeutic efficiency. As a result, a remarkable synergistic tumor chemo/photodynamic/photothermal therapy with hydrangea-structured TME responsive oxygen-self-generation nanoplatform is confirmed by both in vitro and in vivo studies, testifying its great potential for hypoxic tumor treatment in clinical application.
Assuntos
Hydrangea/química , Imagem Multimodal , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Hipóxia Tumoral , Microambiente Tumoral , Animais , Compostos de Boro/química , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Peróxido de Hidrogênio/toxicidade , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Fármacos Fotossensibilizantes/uso terapêutico , Espectrofotometria Ultravioleta , TemperaturaRESUMO
Photoactivated cancer therapeutic methods emerging in recent decades, such as photothermal therapy (PTT) and photodynamic therapy (PDT), have drawn worldwide research interest. Herein, a smart near-infrared (NIR) photosensitizer 4-(4-(7-(4-Bromophenyl)-1,9-bis(3,4-dimethoxyphenyl)-5,5-difluoro-5H-5l4,6l4-dipyrrolo[1,2-c:2',1'-f][1,3,5,2]triazaborinin-3-yl)phenyl)morpholine (MAB) with morpholine decorating on the aza-BODIPY core is synthesized to achieve dual-modal imaging-guided synergistic PDT/PTT, exhibiting a tumor microenvironment (TME) enhanced cancer theranostic performance. The introduction of electron-donating morpholine offers MAB-enhanced intramolecular charge transfer (ICT) and a pronounced red-shift with maximum absorption peak (λmax) at 730 nm. After encapsulating with amphiphilic polymer DSPE-mPEG2000, as-obtained MAB nanoparticles (NPs) with good biocompatibility can enrich targeting in the lysosomes of tumor cells and afterward be activated under the acidic microenvironment inside the lysosome (pH 5.0) to generate intracellular reactive oxygen species (ROS) for enhanced PDT through interruption of photoinduced electron transfer (PET). Through in vitro cytotoxicity assay studies, the half-maximal inhibitory concentration (IC50) of MAB NPs under irradiation with the 730 nm laser is â¼10 µg/mL, indicating an excellent phototherapy effect. Furthermore, an in vivo study illustrates a prominent PDT/PTT synergistic therapeutic effect, and MAB NPs can be rapidly metabolized.