Noninvasive Photothermal Therapy of Nasopharyngeal Cancer Guided by High Efficiency Optical-Absorption Nanomaterial Enhanced by NIR-II Photoacoustic Imaging.

Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.

High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Background: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Visualizing the early-stage testicular torsion by dual-modal photoacoustic and ultrasound imaging.

Delayed treatment of testicular torsion (TT) can lead to permanent loss of reproductive capacity. Photoacoustic imaging (PAI) and ultrasound imaging (USI) was tested for detecting TT at early stage in mice based on PAI-obtained oxygen saturation (sO2), and USI-collected color pixel density (CPD), peak systolic velocity (PSV) and resistance index (RI). For complete TT, both CPD (9.08 % ± 3.084 to almost zero) and sO2 data (70.09 % ± 1.656-59.84 % ± 1.427) showed an significant change 2 h post-torsion. For incomplete TT, sO2 data exhibited a strong time relationship (Mean values: 6 h, 64.83 % ± 1.898; 12 h, 60.67 % ± 3.555; 24 h, 57.85 % ± 3.575; P < 0.05). However, USI-collected CPD, PSV or IR data from the same TT models showed no significant difference. This study indicated that USI and PAI could identify complete TT. Meanwhile, PAI has shown great potential in the diagnosis of incomplete TT within 24 h based on time-related sO2 map.

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.

Combined Photothermotherapy and Chemotherapy of Oral Squamous Cell Carcinoma Guided by Multifunctional Nanomaterials Enhanced Photoacoustic Tomography.

BACKGROUND: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment. METHODS: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy. RESULTS: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues. CONCLUSION: Our research provides a solid demonstration of the potential of DOX-AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.

Photoacoustic imaging as a highly efficient and precise imaging strategy for the evaluation of brain diseases.

Photoacoustic imaging (PAI) is an emerging imaging strategy with a unique combination of rich optical contrasts, high ultrasound spatial resolution, and deep penetration depth without ionizing radiation. Taking advantage of the features mentioned above, PAI has been widely applied to preclinical studies in diverse fields, such as vascular biology, cardiology, neurology, ophthalmology, dermatology, gastroenterology, and oncology. Among various biomedical applications, photoacoustic brain imaging has great importance due to the brain's complex anatomy and the variability of brain disease. In this review, we aimed to introduce a novel and effective imaging modality for diagnosing brain diseases. Firstly, a brief overview of two major types of PAI system was provided. Then, PAI's major preclinical applications in brain diseases were introduced, including early diagnosis of brain tumors, subtle changes in the chemotherapy response, epileptic activity and brain injury, foreign body, and brain plaque. Finally, a perspective of the remaining challenges of PAI was given for future advancements.

In vivo Multi-scale Photoacoustic Imaging Guided Photothermal Therapy of Cervical Cancer based on Customized Laser System and Targeted Nanoparticles.

BACKGROUND: Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years. METHODS: Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents. RESULTS: The obtained PD-FA nanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects. CONCLUSION: In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.

Optical coherence tomography characterizes the roughness and thickness of the heterogeneous layer on cortical bone surface induced by Er:YAG laser ablation at different moisture contents.

BACKGROUND: As an innovative bone ablation tool, pulsed erbium: yttrium-aluminum-garnet (Er:YAG) laser is being used in clinical practice. It faces the same problems as traditional tools: the water content of bone usually changes with the position, while the amount of water spray in the process of laser irradiation is also uncertain. Real-time monitoring of the effects of laser bone ablation is necessary, but effective tools are still lacking. In this study, we examined the feasibility of rapidly and non-destructively evaluating the surface properties of bone after Er:YAG laser irradiation at different moisture contents by optical coherence tomography (OCT). METHODS: Bone specimens (n=90) collected from pig cortical bone were used in this study. All bone specimens had similar volume and surface characteristics after machining. To display the baseline level before Er:YAG laser ablation, a control group (n=10) without dehydration or Er:YAG laser ablation was examined with OCT, scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) spectroscopy. The remaining specimens were randomly divided into four groups (n=20/group) with different moisture content: dried (Group 2 and Group 4) or not dried (Group 1 and Group 3). Pulsed Er:YAG laser (120 mJ/pulse, 20 Hz, 100 µs) was used for perpendicular irradiation with (Group 1 and Group 2) or without (Group 3 and Group 4) water spray. The treated specimens were subjected to SEM, EDX spectroscopy, OCT, and then processed for histological evaluation. RESULTS: After Er:YAG laser ablation, the melting effect was obvious in the SEM results of the dry groups and non-sprayed groups (Groups 2-4). EDX spectroscopy showed that the content of calcium and phosphorus and their ratios remained unchanged in the undried and with water spray group (Group 1) were the closest to the control group. Three-dimensional (3D) OCT could evaluate the depth and shape of ablation grooves. The roughness of the laser-ablated surface could be visualized by extracting the surface lines from cross-sectional OCT images. The results illustrated that the laser ablation with water spray could achieve a smoother surface. Furthermore, OCT results demonstrated that a layer with high image intensity was generated on the bone surface after laser irradiation. The thickness of these layers showed a correlation with whether or not the laser irradiation was sprayed with water. Histology showed that thin eosin-stained layers were created in all experimental groups, which matched well with OCT results of the layers with high image intensity. No denatured layer was observed in the non-irradiated areas of bone tissues. CONCLUSIONS: OCT could rapidly and non-destructively visualize the bone surface before and after Er:YAG laser ablation at four different moisture contents. The morphology of ablation grooves, as well as the roughness and thickness of the heterogeneous layer on the bone surface, could be characterized quantitatively with good correlation with SEM and histology. This study will promote the development of OCT as an efficient and accurate tool for evaluating laser ablation of bone.

Long-term and in vivo assessment of Aß protein-induced brain atrophy in a zebrafish model by optical coherence tomography.

In this study, a neurotoxicity model of zebrafish induced by amyloid beta (Aß) protein was developed and evaluated in vivo by optical coherence tomography (OCT). Aß protein and phosphate buffer saline (PBS) were separately injected into the head of two groups of adult zebrafish (n = 6 per group). Congo-red staining results confirmed that Aß protein had penetrated into brain tissue. All zebrafish were imaged with OCT on the 0th, 5th, 10th, 15th and 20th day postinjection. OCT images showed that PBS is not toxic to brain tissue. However, significant brain atrophy could be seen in the OCT images of zebrafish injected with Aß-protein that was verified by histological consequences. In addition, zebrafish in the model group showed memory decline in behavioral tests. This study verified the feasibility of in vivo long-term assessment of Aß protein-induced brain atrophy in adult zebrafish by OCT that has great potential to be applied in the neurological diseases research.

Donor-acceptor conjugated polymer-based nanoparticles for highly effective photoacoustic imaging and photothermal therapy in the NIR-II window.

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.