Small Molecular Fluorescent Probes: Application Progress of Specific Bacteria Detection and Antibacterial Phototherapy.

Bacterial infection is one of the leading causes of death worldwide and is easy to cause large-scale diseases. It is an urgent need to develop effective methods for the specific detection and treatment of bacterial infections. Recently, small molecular fluorescent probes, bridging the capability of imaging detection and sterilization, have attracted increasing attention. Fluorescence imaging assays have the benefit of being simple, specific, and fast, which is very advantageous in both in vitro and in vivo bacterial detection. Molecularly fluorophores for theranostics provide advantages of non-invasion, high specificity, and fewer side effects. In this review, we summarize the recent advances and design strategies of small molecular fluorescent probes for both targeted detection and treatment of bacteria. We hope that this review will provide guidance for the development of more effective fluorescent dyes in the future as well as encourage preclinical and clinical studies of phototherapy-mediated antimicrobial therapy.

Precision photothermal therapy and photoacoustic imaging by in situ activatable thermoplasmonics.

Phototherapy holds great promise for disease treatment; however, traditional "always-on" photoagents have been restricted to clinical translation due to their nonspecific response and side effects on normal tissues. Here, we show a tumor microenvironment activated photothermal and photoacoustic agent as an activatable prodrug and probe that allows precise cancer diagnosis and treatment. Such an in situ revitalized therapeutic and contrast agent is achieved via controllable plasmonic heating for thermoplasmonic activation. This enables monitoring of signal molecule dynamics, real-time photothermal and photoacoustic imaging of tumors and lymph node metastasis, and targeted photothermal therapy without unwanted phototoxicity to normal tissues. Our study provides a practical solution to the non-specificity problem in phototherapy and offers precision cancer therapeutic and theranostic strategies. This work may advance the development of ultrasensitive disease diagnosis and precision medicine.

Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis.

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment.

Stimuli-responsive multifunctional metal-organic framework nanoparticles for enhanced chemo-photothermal therapy.

Construction of stimuli-responsive multifunctional nanoparticles is critical for nanotherapeutic delivery. Though metal-organic frameworks (MOFs) have been emerged as promising delivery vehicles, the therapeutic efficacy of MOFs in cancer treatment is limited by the lack of a general approach for the preparation of stimuli-responsive multifunctional MOFs. We show that the combination of a versatile coating material polydopamine with MOFs enables facile integration of different functional therapeutics, obtaining stimuli-responsive multifunctional MOFs with extensive photothermal efficiency and outstanding capability to abrogate tumors by chemo-photothermal therapy. Exemplary MOFs including ZIF-8, UiO-66, and MIL-101 were utilized to prepare stimuli-responsive multifunctional MOFs to illustrate the generality of the strategy. This approach enables targeted drug delivery and stimuli-responsive release of multi-therapeutics and allows combination therapy with excellent in vitro and in vivo antitumor activity. Taking into account the diversity of MOFs and different functional molecules, this work provides flexible access to programmable MOF nanoparticles for specific biological applications.

Plasmonic and Photothermal Immunoassay via Enzyme-Triggered Crystal Growth on Gold Nanostars.

Immunoassay is commonly used for the detection of disease biomarkers, but advanced instruments and professional operating are often needed with current techniques. The facile readout strategy for immunoassay is mainly limited to the gold nanoparticles-based colorimetric detection. Here, we show that photothermal nanoparticles can be applied for biosensing and immunoassay with temperature as readout. We develop a plasmonic and photothermal immunoassay that allows straightforward readout by color and temperature based on crystal growth, without advanced equipment. It is demonstrated that alkaline phosphatase-triggered silver deposition on the surface of gold nanostars causes a large blue shift in the localized surface plasmon resonance of the nanosensor, accompanied by photothermal conversion efficiency changes. This approach also allows dual-readout of immunoassays with high sensitivity and great accuracy for the detection of prostate-specific antigen in complex samples. Our strategy provides a promising way for point-of-care testing and may broaden the applicability of programmable nanomaterials for diagnostics.