TiC MXene is a new two-dimensional material exhibiting a variety of novel properties including good photothermal effect, and the capability of TiC for multimodal tumor therapy is in urgent need of development. Herein, ultrathin TiC MXene nanosheets (∼100 nm) have been synthesized by supplying additive Al to avoid Al loss and employed as a photothermal/photodynamic agent for cancer therapy. The as-obtained nanosheets exhibit outstanding mass extinction coefficient (28.6 Lg cm at 808 nm), superior photothermal conversion efficiency (∼58.3%), and effective singlet oxygen generation (O) upon 808 nm laser irradiation. Based on these TiC nanosheets, a multifunctional nanoplatform (TiC-DOX) is established via layer-by-layer surface modification with doxorubicin (DOX) and hyaluronic acid (HA). In vitro and in vivo experiments disclose that TiC-DOX shows enhanced biocompatibility, tumor specific accumulation, and stimuli-responsive drug release behavior and achieve effective cancer cell killing and tumor tissue destruction through photothermal/photodynamic/chemo synergistic therapy.

Developing smart photosensitizers sensitively responding to tumor-specific signals for reduced side effects and enhanced anticancer efficacy is a major challenge for tumor phototherapy. Herein, a pH-sensitive photosensitizer has been synthesized through introducing a pH-sensitive receptor (dimethylaminophenyl unit) onto the aza-BODIPY core (abbreviated as NAB). Through enveloping hydrophobic NAB with amphiphilic DSPE-mPEG 2000 , NAB nanoparticles (NPs, diameter ∼ 30 nm) with strong near-infrared absorption (∼792 nm) are obtained. NAB NPs can be activated in weak acidic environment to give high rate of reactive oxygen species (ROS) generation and enhanced photothermal effect. NAB NPs can selectively accumulate in the lysosomes of tumor cells and subsequently activate under the acidic microenvironment of lysosome (pH 5.0) to produce ROS for photodynamic therapy, due to switch-off of the photoinduced electron transfer (PET) pathway. In vivo, pH-enhanced photoacoustic imaging (PAI) and photothermal imaging (PTI) confirm that NAB NPs can selectively aggregate in the tumor, and the tumor growth can be effectively inhibited under xenon lamp irradiation through synergistic phototherapy (photodynamic and photothermal therapy, PDT/PTT). Furthermore, based on PAI signal and terminal elimination half-life (T 1/2 ) obtained by pharmacokinetic experiment, it is concluded that the NAB NPs can be rapidly metabolized. The pH-sensitive NAB NPs offer a new possibility toward PAI and PTI guided synergistic phototherapy.

Novel photosensitizers have been developed with high 1O2 quantum yields and strong fluorescence for cancer diagnosis and PDT.

BackgroundThe development of potent non-toxic chemotherapeutic drugs against castration resistant prostate cancer (CRPC) remains a major challenge. Corosolic acid (CA), a natural triterpenoid, has anti-cancer activity with limited side effects. However, CA anti-prostate cancer activities and mechanisms, particularly in CRPC, are not clearly understood. In this study, we investigated CA anti-tumor ability against human CRPC and its mechanism of action.MethodsThe cell apoptosis and proliferation effects were evaluated via MTT detection, colony formation assay and flow cytometry. Western blot, gene transfection and immunofluorescence assay were applied to investigate related protein expression of Endoplasmic reticulum stress. A xenograft tumor model was established to investigate the inhibitory effect of CA on castration resistant prostate cancer in vivo.ResultsThe results showed that CA inhibited cell growth and induced apoptosis in human prostate cancer cell (PCa) line PC-3 and DU145, as well as retarded tumor growth in a xenograft model, exerting a limited toxicity to normal cells and tissues. Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. IRE-1, PERK or CHOP knockdown partially attenuated CA cytotoxicity against PCa cells. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. CHOP silencing resulted in PCa cells sensitive to CA-induced apoptosis.ConclusionOur data demonstrated, for the first time, that CA might represent a novel drug candidate for the development of an anti-CRPC therapy.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0889-x) contains supplementary material, which is available to authorized users.

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