This review summarizes the recent advances of optical nano-agents for various biomedical applications in the NIR-II window.

Current surgical treatment for oral squamous cell carcinoma (OSCC) must be as precise as possible to fully resect tumors and preserve functional tissues. Thus, it is urgent to develop efficient fluorescent probes to clearly identify tumor delineation, as well as metastatic lymph nodes. Chemo-photothermal therapy combination attracted a growing attention to increase anti-tumor effect in various types of cancer, including OSCC. In the present study, we designed a multimodal NIR-II probe that involves combining photothermal therapy with chemotherapy, imaging OSCC tumors and detecting metastatic lymph nodes.

Herein, a nano-integrated strategy was used to combine an anti-angiogenic agent sorafenib and a photosensitizer chlorin e6 to form carrier-free multifunctional nanoparticles (SC NPs) for synergetic anti-angiogenic therapy and phototherapy. SC NPs (diameter, ∼152 nm) presented excellent water dispersity and passive targeting ability towards tumor sites in vivo based on the enhanced permeability and retention (EPR) effect, which could be monitored by fluorescence imaging. Besides, SC NPs exhibited effective reactive oxygen species (ROS) generation and photothermal conversion abilities for both photodynamic therapy (PDT) and photothermal therapy (PTT). At a rather low dosage (200 μg kg⁻¹) and illumination with laser (660 nm, 500 mW cm⁻²), SC NPs could attack tumor tissues by killing the internal tumor cells via mild phototherapy, simultaneously cutting off the external nutrient and oxygen supplements of the tumor cells via anti-angiogenesis. Besides, oxygen consumption in the PDT process may be combined with anti-angiogenic therapy to further cause cell apoptosis by tumor starvation. In addition to the highly efficient therapeutic effect in vivo, SC NPs possessed excellent biosafety and biocompatibility, making them promising for fluorescence imaging-guided synergetic anti-angiogenic therapy and phototherapy in clinic.

Periodontitis is a common public health problem worldwide and an inflammatory disease with irregular defect of alveolar bone caused by periodontal pathogens. Both antibacterial therapy and bone regeneration are of great importance in the treatment of periodontitis. In this study, injectable and thermosensitive hydrogels with 3D networks were used as carriers for controlled release of osteo-inductive agent (BMP-2) and Near Infrared Region-II (NIR-II) phototherapy agents (T8IC nano-particles). T8IC nano-particles were prepared by reprecipitation and acted as photosensitizer under 808 nm laser irradiation. Besides, we promoted photodynamic therapy (PDT) through adding H₂O₂ to facilitate the antibacterial effect instead of increasing the temperature of photothermal therapy (PTT). Hydrogel + T8IC + Laser + BMP-2 + H₂O₂ incorporated with mild PTT (45 °C), enhanced PDT and sustained release of BMP-2. It was present with excellent bactericidal effect, osteogenic induction and biosafety both in vitro and in vivo. Besides, immunohistochemistry staining and micro-CT analyses had confirmed that PTT and PDT could promote bone regeneration through alleviating inflammation state. Altogether, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future.

Background: Tumor microenvironment plays an important role in the chemoresistance of oral squamous cell carcinoma (OSCC). Hypoxia in the microenvironment is one of the important factors that contributes to OSCC chemoresistance; therefore overcoming hypoxia-mediated chemoresistance is one of the great challenges in clinical practice. Methods: In this study, we developed a drug delivery system based on Pt-loaded, polyethylene glycol-modified graphene quantum dots via chemical oxidation and covalent reaction. Results: Our results show that synthesized polyethylene glycol-graphene quantum dots-Pt (GPt) is about 5 nm in diameter. GPt sensitizes OSCC cells to its treatment in both normoxia and hypoxia conditions. Inductively coupled plasma-mass spectrometry assay shows that GPt enhances Pt accumulation in cells, which leads to a notable increase of S phase cell cycle arrest and apoptosis of OSCC cells in both normoxia and hypoxic conditions. Finally, compared with free cisplatin, GPt exhibits a strong inhibitory effect on the tumor growth with less systemic drug toxicity in an OSCC xenograft mouse tumor model. Conclusion: Taken together, our results show that GPt demonstrates superiority in combating hypoxia-induced chemoresistance. It might serve as a novel strategy for future microenvironment-targeted cancer therapy.

Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment Crosstalk between the HIF-1 and toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment