A tailored and red-emissive type I photosensitizer to potentiate photodynamic immunotherapy.

Photodynamic immunotherapy (PDIT) has emerged as a technique which shows great potential in eradicating malignant tumors due to its advantages of simultaneously damaging primary tumors and inhibiting tumor metastasis and recurrence. However, the hypoxic microenvironment of tumor tissue and immune escape are two major challenges that PDIT faces. Hence, a well-designed water-soluble type I photosensitizer (TbT-TPP) based on a "D-A" strategy is reported for imaging-guided PDIT. The enhanced dihedral angle, prolonged conjugation length, strong electron withdrawing effect, and electron-rich condition endow TbT-TPP with a superior type I ROS generation ability and aggregation-induced red emission, which is demonstrated by comparision with the control molecule. We demonstrate that in hypoxic tissue, TbT-TPP can light up tumors and further efficiently kill them, triggering immunogenic cell death by generating type I ROS, which sequentially promotes the maturation of dendritic cells and enhances the T-cell response to tumor cells. Combined with immune adjuvant R837, TbT-TPP based-PDIT achieves the complete elimination of solid tumors and inhibition of tumor metastasis of living mice. This work provides a potential theranostic material and new insights into the improvement of PDIT against hypoxic tumors.

Multifunctional Self-Assembly with NIR Light-Activated Cascade Effect for Improving Local Treatment on Solid Tumors.

Incomplete local treatment of solid tumors is the main cause of tumor difficult to cure, and easily leads to tumor metastasis and recurrence. The dense external matrix and hypoxic microenvironment of solid tumors severely restrict the therapy efficacy of local tumors. Enhancing the infiltration ability of agents to tumor tissues and adapting the therapy mode favored to hypoxic microenvironments are beneficial to improve the cure rate of tumors. In this work, we designed and developed a self-assembled biomaterial with a cascade effect triggered by near-infrared light. The self-assembly was combined of biotin, phase change material (PNIPAM), photochemical agent (ATT-2), and alkyl radical generator (AIPH). In the assembly, biotin acted as a targeted group. ATT-2 was used to provide heat to synergistically induce the phase change and decompose alkyl radicals. The superficial and deep tumors were ablated by heat and alkyl radicals with white light irradiation of the assembly, respectively. The assay in vivo showed that the self-assembly could effectively eliminate local lesions of solid tumors. This work provides new insights for improving the cure rate of tumors, which not only develops biomaterials adapted to the tumor microenvironment, but also proposes new therapies for complete elimination of solid tumors.

Intelligent Hybrid Hydrogels for Rapid In Situ Detection and Photothermal Therapy of Bacterial Infection.

Diseases induced by bacterial infections increasingly threaten the health of people all over the world; thus, it is urgent and significant to early diagnose and effectively eliminate infections to save people's lives. To this end, we synthesized an intelligent hydrogel that integrated in situ visualized diagnosis and photothermal therapy of bacterial infections. By simply and subtly incorporating pH-sensitive bromothymol blue (BTB) and near-infrared (NIR)-absorbing conjugated polymer (termed as PTDBD) into thermosensitive chitosan (CS)-based hydrogel, the synthesized BTB/PTDBD/CS hydrogel can diagnose the acidic microenvironment of Staphylococcus aureus (S. aureus) biofilm and infected wounds by showing visualized color change. After rapid diagnosis, the hydrogel can immediately treat the infection site by local hyperthermia under irradiation of NIR laser (808 nm) and even the stubborn biofilm that is difficult to eradicate. Since the dominating antibacterial mechanism is hyperthermia, the hybrid hydrogel shows broad-spectrum antibacterial activity against Gram-positive, Gram-negative, and drug-resistant bacteria. In addition, it has low cytotoxicity to normal cells and no effect on the main organs of mice. It paves a brand new avenue to develop smart and facile diagnosis and a treatment platform for bacterial infections.

Near-Infrared Light-Triggered Synergistic Phototherapy for Antimicrobial Therapy.

Phototherapy has great advantages in combating bacterial infection, in particular, those therapies mediated by near-infrared light. To advance phototherapy for bacterial infections, a positively charged conjugated polymer (termed PTDBD) with near-infrared light-triggered activity is employed for antimicrobial therapy in this paper. The quaternary ammonium groups in side chains of PTDBD can benefit from the interaction between the polymer and negatively charged membrane of bacteria, and such a structure can also induce the aggregation of bacteria to improve local antibacterial efficiency. Upon single near-infrared light irradiation, simultaneous reactive oxygen species (ROS) and heat generated by the polymer PTDBD can effectively kill bacteria at low treatment concentration (40 µg·mL-1) and low light density (1.0 W·cm-2) toward both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (ampicillin-resistant Escherichia coli TOP 10). For fungi (Candida albicans), a higher treatment concentration of PTDBD is needed to kill at the same light density. Finally, the dual phototherapy is also employed to treat the bacteria-infected wound of mice with no tissue damage observed. The integration of positive charges, ROS, and heat provides a highly efficient and broad spectrum antimicrobial strategy for further treatment of bacterial infections in vivo.

Water-soluble conjugated polymer with near-infrared absorption for synergistic tumor therapy using photothermal and photodynamic activity.

A novel near-infrared absorbing photo-agent based on a water-soluble conjugated polymer (PTDBD) is reported for synergetic photothermal/photodynamic therapy with single near-infrared light (808 nm) irradiation. In vitro and in vivo studies demonstrated the superior therapeutic effect of the single NIR-irradiated PTT/PDT by using PTDBD.

A high brightness probe of polymer nanoparticles for biological imaging.

Conjugated polymer nanoparticles (CPNs) with high brightness in long wavelength region were prepared by the nano-precipitation method. Based on fluorescence resonance energy transfer (FRET) mechanism, the high brightness property of the CPNs was realized by four different emission polymers. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) displayed that the CPNs possessed a spherical structure and an average diameter of ~75nm. Analysis assays showed that the CPNs had excellent biocompatibility, good photostability and low cytotoxicity. The CPNs were bio-modified with a cell penetrating peptide (Tat, a targeted element) through covalent link. Based on the entire wave fluorescence emission, the functionalized CPNs1-4 can meet multichannel and high throughput assays in cell and organ imaging. The contribution of the work lies in not only providing a new way to obtain a high brightness imaging probe in long wavelength region, but also using targeted cell and organ imaging.