Oral cancer is a common malignant tumor of the head and neck, and surgery combined with radiotherapy and chemotherapy is the primary treatment modality. However, a positive resection margin that may lead to recurrence after surgery has always been a critical issue to address. Furthermore, radiotherapy and chemotherapy also have shortcomings such as resistance to chemotherapy and radiation, lack of targeting, and severe side effects. Therefore, exploring new methods of tumor surgical navigation and tumor treatment is of great significance for oral cancer. Although, the emerging near-infrared II (NIR-II, 1,000–1,700 nm) region fluorescent imaging has revolutionized surgical navigation, a high tumor-targeting fluorescent probe remains lacking. Furthermore, while emerging photothermal therapy (PTT) can overcome chemoradiotherapy’s shortcomings and achieve precise treatment of tumors, its clinical application is still limited by the lack of high photothermal conversion efficiency, high photothermal stability, and highly penetrating materials. Herein, a NIR-II dye SQ890 is developed for tumor imaging and PTT of oral cancer. By assembling into nanoparticles (NPs) and being modified with epithelial growth factor receptor (EGFR)-targeting peptides GE11, SQ890 NPs-Pep can specifically accumulate in tumor sites via active targeting, and realize photoacoustic/NIR-II fluorescence dual-modality imaging-guided PTT of oral cancer.

Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels (^CDDPHANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA- crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo, ^CDDPHANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.