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.

Herein, a donor-acceptor-donor (D-A-D) structured small molecule (DPP-TPA) is designed and synthesized for photoacoustic imaging (PAI) guided photodynamic/photothermal synergistic therapy. In the diketopyrrolopyrrole (DPP) molecule, a thiophene group is contained to increase the intersystem crossing (ISC) ability through the heavy atom effect. Simultaneously, triphenylamine (TPA) is introduced for bathochromic shift absorption as well as charge transport capacity enhancement. After formation of nanoparticles (NPs, ∼76 nm) by reprecipitation, the absorption of DPP-TPA NPs further displays obvious bathochromic-shift with the maximum absorption peak at 660 nm. What's more, the NPs architecture enhances the D-A-D structure, which greatly increases the charge transport capacity and impels the charge to generate heat by light. DPP-TPA NPs present high photothermal conversion efficiency (η = 34.5%) and excellent singlet oxygen (O) generation (Φ = 33.6%) under 660 nm laser irradiation. PAI, with high spatial resolution and deep biotissue penetration, indicates DPP-TPA NPs can rapidly target the tumor sites within 2 h by the enhanced permeability and retention (EPR) effect. Importantly, DPP-TPA NPs could effectively hinder the tumor growth by photodynamic/photothermal synergistic therapy in vivo even at a low dosage (0.2 mg/kg) upon laser irradiation (660 nm 1.0 W/cm). This study illuminates the photothermal conversion mechanism of small organic NPs and demonstrates the promising application of DPP-TPA NPs in PAI guided phototherapy.

Heavy atom effect and configuration are important for BODIPY derivatives to generate singlet oxygen (O) for photodynamic therapy. Herein, a series of BODIPY derivatives with different halogens were synthesized. O quantum yields (QYs) and MTT assay confirm that incorporation of more heavy atoms onto dimeric BODIPY cannot effectively enhance the O QYs. Rather, the dark toxicity increases. This phenomenon can be attributed to the competition of heavy atom effect and configuration of dimeric BODIPY. In addition the BODIPY derivative with two iodine atoms (BDPI) owns the highest O QYs (73%) and the lowest phototoxicity IC (1 μM). Furthermore, an in vivo study demonstrates that BDPI NPs can effectively inhibit tumor growth and can be used as a promising threanostic agent for photodynamic therapy in clinic.