A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma

Abstract

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. Methods : In this study, we synthesized a novel near infrared (NIR)-II probe named TQTPA [4,4'-((6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo [3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-diphenylaniline)] via the Suzuki reaction and prepared multimodal nanoparticles (NPs) loading TQTPA and cis -dichlorodiammine platinum (CDDP) (HT@CDDP) by hyaluronic acid. The characteristics of the NPs, including their photothermal and imaging capabilities were investigated in vitro and in vivo . Their anti-tumor efficacy was evaluated using orthotopic, tongue tumor-bearing, nude mice. Results : The NPs possessed good stability and water solubility and were pH/hyaluronidase sensitive. The good tissue penetration quality and active targeting ability enabled the NPs to draw the outline of orthotopic tongue tumors and metastatic lymph nodes as small as 1 mm in nude mice by IR-808 under NIR exposure. In vitro and in vivo experiments validated the biocompatibility and low systematic toxicity of the NPs. At the same time, the NPs acted as multimodal therapy agents, combining photothermal therapy with chemotherapy. Conclusion : With a good imaging capability and anti-tumor efficacy, our NPs successfully outlined orthotopic tongue tumors and metastatic lymph nodes as well as enabled chemo-photothermal therapy combination. Our study established a solid foundation for the application of new clinical diagnosis and treatment patterns in the future.

Image‐guided tumor surgery: The emerging role of nanotechnology

“…A multifunctional NP termed HT@CDDP was capable as a theranostic agent for oral squamous cell carcinoma. HT@CDDP provided sufficient tumor contrast up to 24 hr after injection while also suppressing tumor growth with combinatorial chemo‐PTT (Wang et al, ).…”

<p>Facile Synthesis of Melanin-Dye Nanoagent for NIR-II Fluorescence/Photoacoustic Imaging-Guided Photothermal Therapy</p>

“…33 Photothermal stability is another important parameter for evaluating the photothermal agents. 3,53 The MNPH2 solution was exposed to an 808 Figure 3D. The time constant for heat transfer of the MNPH2 was calculated to be 243 s. (F) Photothermal stability of MNPH2 (100 μg/mL) in DI water upon irradiation for six cycles (808 nm, 0.5 W/cm 2 ).…”

“…A novel fluorescence imaging approach in the second NIR window (NIR-II, 1000-1700 nm) provides deeper tissue penetration (~10 mm), a higher signal-tonoise ratio, and better spatial resolution than NIR-I because of minimal photon scattering and tissue autofluorescence. 2 Recent studies, including those regarding the detection of metastatic lymph nodes, 3 tumor and vessel imaging, [4][5][6] and intraoperative guidance, 7,8 have shown that biological imaging advantages significantly improves as wavelengths increase. Thus far, quantum dots, [9][10][11] carbon nanotubes, 12,13 rare earth-doped nanoparticles, 14,15 squaraine dyes, 16,17 semiconducting polymer nanoparticles, 18 and small-molecule dyes 5,19,20 have all been actively used for NIR-II imaging.…”

“…0×10 6 cells) were subcutaneously implanted on the dorsum region of the right leg to generate tumor-bearing nude mice. When the tumors reached about 100 mm3 , these nude mice were conducted for imaging and therapy studies.…”

Photonic hyperthermal and sonodynamic nanotherapy targeting oral squamous cell carcinoma

“…The present research in the field of nanomedicine for OSCC treatment is mostly focused on PTT with chemotherapy. 30,31 Statistical data have shown that, over the past 40 years, the application of cytotoxic chemotherapeutic drugs has not significantly ameliorated the survival or life quality of patients with oral cancer. 32,33 Therefore, exploring new synergistic therapeutic modalities to achieve safe and effective treatment for OSCC, as well as to ameliorate the prognosis, is highly urgent and necessary.…”