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.