Multi-Modal Optical Imaging and Combined Phototherapy of Nasopharyngeal Carcinoma Based on a Nanoplatform.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck with a high incidence rate worldwide, especially in southern China. Phototheranostics in combination with nanoparticles is an integrated strategy for enabling simultaneous diagnosis, real-time monitoring, and administration of precision therapy for nasopharyngeal carcinoma (NPC). It has shown great potential in the field of cancer diagnosis and treatment owing to its unique noninvasive advantages. Many Chinese and international research teams have applied nano-targeted drugs to optical diagnosis and treatment technology to conduct multimodal imaging and collaborative treatment of NPC, which has become a hot research topic. In this review, we aimed to introduce the recent developments in phototheranostics of NPC based on a nanoplatform. This study aimed to elaborate on the applications of nanoplatform-based optical imaging strategies and treatment modalities, including fluorescence imaging, photoacoustic imaging, Raman spectroscopy imaging, photodynamic therapy, and photothermal therapy. This study is expected to provide a scientific basis for further research and development of NPC diagnosis and treatment.

Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head and neck malignant tumor with a high incidence in specific regional distribution, and its traditional therapies face some challenges. It has become an urgent need to seek new therapeutic strategies without or with low toxicity and side effects. At present, more and more researchers has been attracting attention by nanotheranostic platform. Therefore, our team synthesized the polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X (USPIO-PEG-sLex) nanotheranostic platform with high temperature pyrolysis. RESULTS: The USPIO-PEG-sLex nanoparticles had excellent photothermal conversion property, and the temperature of USPIO-PEG-sLex nanoparticles solution increased with its concentration and power density of near-infrared (NIR) on 808 nm wavelengths. Five USPIO-PEG-sLex nanoparticles with different concentrations of 0 mg/ml, 0.025 mg/ml, 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml were prepared. The biological toxicity results showed that the viability of NPC 5-8F cells is related to the concentration of USPIO-PEG-sLex nanoparticles and the culture time (P < 0.001). The results of photothermal therapy (PTT) in vitro indicated that the viability of 5-8F cells decreased significantly with the concentration of USPIO-PEG-sLex nanoparticles increases (P < 0.001), and the viability of NPC 5-8F cells were 91.04% ± 5.20%, 77.83% ± 3.01%, 73.48% ± 5.55%, 59.50% ± 10.98%, 17.11% ± 3.14%, respectively. The USPIO-PEG-sLex nanoparticles could target the tumor area, and reduce the T2* value of tumor tissue. The T2* values of tumor pre- and post-injection were 30.870 ± 5.604 and 18.335 ± 4.351, respectively (P < 0.001). In addition, USPIO-PEG-sLex nanoparticles as a photothermal agent for PTT could effectively inhibit tumor progression. The ratio of volume change between tail vein injection group, control group, nanoparticles without laser irradiation group and blank group after 5 treatments were 3.04 ± 0.57, 5.80 ± 1.06, 8.09 ± 1.96, 7.89 ± 2.20, respectively (P < 0.001). CONCLUSIONS: Our synthesized USPIO-PEG-sLex nanotheranostic platform, and it may be become a new strategy for the treatment of NPC.

Deep learning for risk prediction in patients with nasopharyngeal carcinoma using multi-parametric MRIs.

BACKGROUND: Magnetic resonance images (MRI) is the main diagnostic tool for risk stratification and treatment decision in nasopharyngeal carcinoma (NPC). However, the holistic feature information of multi-parametric MRIs has not been fully exploited by clinicians to accurately evaluate patients. OBJECTIVE: To help clinicians fully utilize the missed information to regroup patients, we built an end-to-end deep learning model to extract feature information from multi-parametric MRIs for predicting and stratifying the risk scores of NPC patients. METHODS: In this paper, we proposed an end-to-end multi-modality deep survival network (MDSN) to precisely predict the risk of disease progression of NPC patients. Extending from 3D dense net, this proposed MDSN extracted deep representation from multi-parametric MRIs (T1w, T2w, and T1c). Moreover, deep features and clinical stages were integrated through MDSN to more accurately predict the overall risk score (ORS) of individual NPC patient. RESULT: A total of 1,417 individuals treated between January 2012 and December 2014 were included for training and validating the end-to-end MDSN. Results were then tested in a retrospective cohort of 429 patients included in the same institution. The C-index of the proposed method with or without clinical stages was 0.672 and 0.651 on the test set, respectively, which was higher than the that of the stage grouping (0.610). CONCLUSIONS: The C-index of the model which integrated clinical stages with deep features is 0.062 higher than that of stage grouping alone (0.672 vs 0.610). We conclude that features extracted from multi-parametric MRIs based on MDSN can well assist the clinical stages in regrouping patients.

The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem.

Treatment failure occurs in more than 40% of advanced nasopharyngeal carcinoma (NPC) patients including local recurrence and distant metastasis due to chemoradioresistance. Circadian clock genes were identified as regulating cancer progression and chemoradiosensitivity in a time-dependent manner. A novel nanosystem can ensure the accumulation and controllable release of chemotherapeutic agents at the tumour site at a set time. In this study, we investigated the expression of circadian clock genes and identified that period circadian regulator 2 (PER2) as a tumour suppressor plays a key role in NPC progression. A label-free proteomic approach showed that PER2 overexpression can inhibit the ERK/MAPK pathway. The chemotherapeutic effect of PER2 overexpression was assessed in NPC together with the nanosystem comprising folic acid (FA), upconverting nanoparticles covalently coupled with Rose Bengal (UCNPs-RB), 10-hydroxycamptothecin (HCPT) and lipid-perfluorohexane (PFH) (FURH-PFH-NPs). PER2 overexpression combined with the targeted and controlled release of nanoagents elevated chemotherapeutic efficacy in NPC, which has potential application value for the chronotherapy of tumours.

Highly Uniform Synthesis of Selenium Nanoparticles with EGFR Targeting and Tumor Microenvironment-Responsive Ability for Simultaneous Diagnosis and Therapy of Nasopharyngeal Carcinoma.

Rational design of multifunctional and smart drug-delivered nanoplatforms is a promising strategy to achieve simultaneous diagnosis, real-time monitoring, and therapy of cancers. Herein, highly uniform and stable selenium nanoparticles with epidermal growth factor receptor (EGFR) targeting and tumor microenvironment-responsive ability (Se-5Fu-Gd-P(Cet/YI-12)) were designed and synthesized by using EGFR as the targeting molecule, gadolinium chelate as the magnetic resonance imaging contrast agent, 5-fluorouracil (5Fu) and cetuximab as drug payloads, polyamidoamine (PAMAM) and 3,3'-dithiobis (sulfosuccinimidyl propionate) as the response agents of intratumoral glutathione, and pH for the treatment and diagnosis of nasopharyngeal carcinoma (NPC). This Se nanoplatform showed excellent magnetic resonance imaging capability and has the potential for its clinical application as a diagnostic agent for tumor tissue specimens. Additionally, in vitro cellular experiments showed that by means of introducing clinical targeted drugs and peptides not only validly increased the intracellular uptake of the Se nanoplatform in NPC cells but also enhanced its penetration ability toward CNE tumor spheroids, resulting in simultaneous inhibition of CNE cell growth, invasion, and migration. In addition, the sequentially triggered bioresponsive property of the nanoplatform in a tumor microenvironment effectively improved the targeting delivery and anticancer efficiency of payloads. Overall, this study not only provides a strategy for facile synthesis of highly uniform and stable nanomedicines and tailing of the bioresponsive property but also sheds light on its application in targeting theranosis of NPC.

Radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma patients: A dose-volume-outcome analysis.

OBJECTIVE: This is a retrospective dose-volume-outcome analysis of radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma (NPC) patients, with the aim to determine how the radiation doses to nasopharynx influence the occurence of radiation-induced nasopharyngeal ulcer (RINU) and predict the most serious complication of radiotherapy for NPC. METHODS: Data from 6023 consecutive and nonselected histologically proven primary NPC patients treated with definitive IMRT were collected and 25 patients were diagnosed with nasopharyngeal ulcer and met the diagnosis criteria of RINU. Predictive dosimetric factors were identified by using univariate and multivariate analysis. RESULTS: Paired samples t-tests showed all dosimetric factors were significantly correlated with the development of RINU, and these factors were associated with each other closely. (P < 0.001) Multivariate analysis revealed D3cc (dose to 3 mL of the nasopharynx) was an independent predictor for RINU (P = 0.01); the area under the ROC curve for D3cc was 0.87 (P < 0.001), and the cutoff point 73.67 Gy may be the dose tolerance of the nasopharynx. The primary tumor location, distribution of high dose regions and the location of RINU were consistent. CONCLUSIONS: The study indicates that radiation-induced nasopharyngeal ulcer is consistent with primary tumor location and 'hottest spots' regions and we suggest a D3cc limit of 73.67 Gy for the nasopharynx. Physicians should be cautious of such 'hot spots' in the nasopharynxduring IMRT treatment plan optimization, review and approval to avoid the most serious complication of radiotherapy for NPC.