Deep Tumor Imaging Research Articles

ICG Functionalized Gold Nano Stars Allow for Delivery of Therapeutics and Deep Tumor Imaging Intraoperatively

ICG Functionalized Gold Nano Stars Allow for Delivery of Therapeutics and Deep Tumor Imaging Intraoperatively

Persistent luminescence nanoparticles with high intensity for colorectal cancer surgery navigation and precision resection.

Surgical resection remains the main treatment for malignant tumors. Image-guided surgery aims to remove tumor tissue completely while preserving normal tissue, thereby reducing tumor recurrence rates and injury. However, challenges like tissue autofluorescence, limited probe penetration and low contrast restrict its use. Near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) provide a solution by emitting persistent luminescence (PersL) even after excitation ceases, thus circumventing autofluorescence and enabling deep tumor imaging. In this study, we prepared nano-sized (140 nm hydrodynamic size) Cr3+ doped zinc gallogermanate (ZGC) using a removable template method and modified it with folate acid to obtain ZGC-FA, which exhibits NIR (695 nm) PersL with a signal-to-noise ratio of 23.9 in vivo. We utilized a colon cancer model that selectively expressed luciferase for the first time to validate the guiding efficacy of ZGC-FA in precision surgical resection. Post-intraperitoneal injection at 50 minutes, the PersL closely matched the tumor boundaries, achieving an overlap rate of approximately 98%. Complete tumor resection was achieved under PersL guidance, with only 2.3% of healthy tissue removed. This research underscores the potential of ZGC-FA in the field of surgical oncology. The precision of the ZGC-FA guided surgical approach holds promise to enhance surgical outcomes and facilitate postoperative recovery in patients.

Nanosized Janus AuNR-Pt Motor for Enhancing NIR-II Photoacoustic Imaging of Deep Tumor and Pt2+ Ion-Based Chemotherapy

Synthetic micro/nanomotors have great potential in deep tissue imaging and in vivo drug delivery because of their active motion ability. However, applying nanomotors with a size less than 100 nm to in vivo imaging and therapy is one of the core changes in this field. Herein, a nanosized hydrogen peroxide (H2O2)-driven Janus gold nanorod-platinum (JAuNR-Pt) nanomotor is developed for enhancing the second near-infrared region (NIR-II) photoacoustic (PA) imaging of deep tissues of tumors and for effective tumor treatment. The JAuNR-Pt nanomotor is prepared by depositing platinum (Pt) on one end of a gold nanorod with varying proportions of Pt shell coverage, including 10%, 25%, 50%, 75%, and 100%. The JAuNR-Pt nanomotor with Pt shell coverage proportions of 50% exhibits the highest diffusion coefficient (De), and it can rapidly move in the presence of H2O2. The self-propulsion of JAuNR-Pt nanomotor enhances cellular uptake, accelerates lysosomal escape, and facilitates continuous release of cytotoxic Pt2+ ions to the nucleus, causing DNA damage and cell apoptosis. The JAuNR-Pt nanomotor presents deep penetration and enhanced accumulation in tumors as well as high tumor treatment effect. Therefore, this work displays deep tumor imaging and an excellent antitumor effect, providing an effective tool for accurate diagnosis and treatment of diseases.

X-ray-Activated Simultaneous Near-Infrared and Short-Wave Infrared Persistent Luminescence Imaging for Long-Term Tracking of Drug Delivery.

Both short-wave infrared (SWIR: 900-1700 nm) and near-infrared (NIR: 650-900 nm) luminescence possess lower optical scattering and higher signal-to-noise in deep tissues than conventional luminescence, gaining increasing attention in biomedicine. Herein, we designed mesoporous silica-coated Yb-doped magnesium germanate nanoparticles (mMGOs) with excellent two-in-one NIR and SWIR persistent luminescence after X-ray irradiation by simply regulating the valence of rare-earth ions, which also possess high cargo loading and a controlled release profile in the tumor region. The investigations in vitro and in vivo showed that mMGOs were repeatedly activated to realize rechargeable persistent luminescence imaging for tracking cargo delivery in mice. Moreover, the stimulative drug-release profile inhibited tumor growth effectively. Both of the X-ray excited two-in-one NIR and SWIR persistent luminescence imaging not only allowed for rechargeable imaging of deep tumors but also achieved long-term tracking with a remarkable tumor inhibition effect.

Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging.

Indocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named "therapeutic window" in the tissue engineering. Unfortunately, rapid elimination and short-term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l-lactic acid) and poly(ε-caprolactone) via a simple one-step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa-2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG-encapsulated multiaxial nanofiber mats. ICG-encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG-loaded nanoparticles in systemic administration.

Large depth focus-tunable photoacoustic tomography based on clinical ultrasound array transducer

Multi-element photoacoustic tomography systems have either a non-movable focus or a non-uniform light field distribution over the region of interest, significantly limiting the depth-of-field and resolution of images. In this study, focus-tunable photoacoustic tomography (FT-PAT) based on a clinical ultrasound array transducer with uniform laser excitation was developed to achieve high-resolution imaging in deep tissue. An adjustable line-focusing structure was used to condense the laser beam, and the excited photoacoustic signal was processed via a synthetic-aperture focusing technique. Carbon rods at different depths were used to evaluate the focus-tunable ability in a tissue phantom. In vivo focus-tunable imaging performance was demonstrated by an experiment involving imaging of carbon nanoparticle-labeled living nude mouse covered by chicken breast. The signal-to-noise ratio of targets at different depths was changed by focus adjustment, which demonstrates that the FT-PAT system has potential clinical applications in deep tumor imaging and subsequent diagnoses.

Deep tumor imaging by upconversion nanoparticles

In this work are shown the prospects of using upconversion nanoparticles (UCNPs) as markers for contrast optical imaging of a tumor. For using nanoparticles for biomedical purposes is implemented a technique for coating nanoparticles with polymers, such as PEG and PSA. This approach provides low non-specific adsorption, which prolongs the circulation of UCNPs in mouse bearing Lewis Lung Cancer (LLC) up to 10 hours. These properties allow nanoparticles to quickly accumulate in the tumor. Effective delivery of particles with different polymer coatings in the tumor is demonstrated with the help of an epiluminescent imaging system.

Single wavelength light-mediated, synergistic bimodal cancer photoablation and amplified photothermal performance by graphene/gold nanostar/photosensitizer theranostics.

This work demonstrated the application of graphene-Au Nanostars hybridized system (denoted as GO/AuNS-PEG) in single wavelength laser induced synergistic photodynamic (PDT) and photothermal therapy (PTT) and effective cancer photothermal/fluorescence multimode imaging. GO/AuNS-PEG showed excellent biocompatibility and high dual-enhanced photothermal efficiency under the near-infrared laser irradiation that was very promise for deep tumor imaging. By combining with the photosensitizer Chlorin e6, both in vitro and in vivo data confirmed the efficient photoablation of the EMT6 tumors through the synergistic PDT and PTT effect under the activation of a single wavelength laser.

Highly efficient NIR to NIR upconversion of ZnMoO4:Tm3+,Yb3+ phosphors and their application in biological imaging of deep tumors.

ZnMoO4:Tm3+,Yb3+,K+ nano-phosphors with intense NIR to NIR (excitation by 980 nm, emission at ∼800 nm) upconversion were synthesized by a facile hydrothermal method. The nanoparticles were of the order of 200-400 nm. The XRD patterns confirmed a single phase triclinic structure despite doping small amounts of RE3+ and alkali ions. The optimum concentration of Tm3+, Yb3+ and alkali ions were determined to be 0.1 mol%, 10 mol% and 10 mol%, respectively. Besides charge neutrality, the doped K+ ions affected the crystal field symmetry around the Tm3+ ions which increased the f-f transition probabilities of the RE3+ ions, and hence increased the UC intensities. Compared with ZnMoO4:Tm3+,Yb3+, the NIR to NIR upconversion emission intensity of 10 mol% K+ substituted ZnMoO4:Tm3+,Yb3+ nanocrystals increased by 21-fold and can be pumped by less than 1 mW laser power. The brightest ZnMoO4:Tm3+,Yb3+,K+ nano-phosphor was applied for non-invasively visualizing the tumors in nude mice and successfully detected deep tumors in the thigh muscles. So far, this is the first report of oxide based UCNPs used for in vivo NIR-to-NIR biological imaging and opens the door to the possibility of achieving improved features using non-fluoride based UCNPs.

Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications.

Photoacoustic imaging (PAI), a novel imaging modality based on photoacoustic effect, shows great promise in biomedical applications. By converting pulsed laser excitation into ultrasonic emission, PAI combines the advantages of optical imaging and ultrasound imaging, which benefits rich contrast, high resolution and deep tissue penetration. In this paper, we introduced recent advances of contrast agents, applications, and signal enhancement strategies for PAI. The PA contrast agents were categorized by their components, mainly including inorganic and organic PA contrast agents. The applications of PAI were summarized as follows: deep tumor imaging, therapeutic responses monitoring, metabolic imaging, pH detection, enzyme detection, reactive oxygen species (ROS) detection, metal ions detection, and so on. The enhancement strategies of PA signals were highlighted. In the end, we elaborated on the challenges and provided perspectives of PAI for deep-tissue biomedical applications.

Perylene-diimide-based nanoparticles as highly efficient photoacoustic agents for deep brain tumor imaging in living mice.

In order to promote preclinical and clinical applications of photoacoustic imaging, novel photoacoustic contrast agents are highly desired for molecular imaging of diseases, especially for deep tumor imaging. Here, perylene-3,4,9,10-tetracarboxylic diiimide-based near-infrared-absorptive organic nanoparticles are reported as an efficient agent for photoacoustic imaging of deep brain tumors in living mice with enhanced permeability and retention effect.

EP-1721: Inverse heat source problem for deep tumor imaging

EP-1721: Inverse heat source problem for deep tumor imaging

Effectiveness of Functionalized Nanosystems for Multimodal Molecular Sensing and Imaging in Medicine

Successful employment of multimodal molecular imaging for cancer targeting entails the development of safe nanoparticle contrast agents (NPCAs), detects at least by two nonionizing imaging techniques. This paper presents a quantitative assessment of the effectiveness of both pure silica nanospheres (SiNSs) and composite silica/superparamagnetic NPCAs as scatterers for low-frequency diagnostic ultrasound (US) (3 MHz) in very low range of concentrations (1.5-5 mg/mL). Iron oxide (IO) and FePt-IO nanocrystals are employed for SiNS magnetic coating. Different samples of NPCA-containing agarose gel are US imaged through a commercially available system and acquired data are processed through a dedicated prototypal platform to extract image backscatter information and perform evaluation of the image gray level. The pure silica NPCAs confirms recent reports for higher concentrations at higher frequencies. The FePt-IO-coated NPCAs show similar behavior, although with lower values of image backscatter, with a marked effectiveness peak for 330-nm SiNSs, particularly useful for tumor targeting purposes. Finally, the IO-coated SiNSs presented a marked lowering of US enhancement potential and a peak efficiency for a particle diameter of 660 nm. The extent of US backscatter reduction is found to be a function of the number of magnetic nanoparticles per mL of NPCA-containing gel and decreased with increasing NPCA concentrations. These results broadened our knowledge of dual-mode molecular imaging of deep tumors, employing US, and magnetic resonance techniques for the accurate, safe and early detection of cancer cells located in internal organs.

Dynamic imaging of cancer invasion, plasticity, and resistance

Molecular programs controlling metastatic cancer progression are diverse in different cancers as well as within the microenvironment of a single lesion. Multiphoton microscopy (MPM) has become the method of choice for investigating cell structure and function in tissues and organs, including the invasion and progression of cancer lesions. Using a novel approach of infrared‐excited (IR‐)MPM at wavelengths above 1080 nm that enhances deep tissue microscopy in orthotopic fibrosarcoma and melanoma xenografts, we here show deep collective invasion of hundreds of connected cells. These multicellular masses proliferate and simultaneously move with velocities of up to 200 μm per day along pre‐existing blood vessels but not tumor‐induced neovessels and proliferate (“invasive growth”). Collective invasion strands further maintain invasion and robust survival during otherwise regression‐inducing experimental radiation therapy. Both, primary growth and survival and increased resistance to experimental therapy were ablated by interfering with beta1/beta3 integrins, implicating integrin‐mediated signals as microenvironmental denoinators of response to therapy. In conclusion, intravital deep tumor imaging by IR‐MPM identifies the tumor‐vessel interface as preferred niche of invasive growth, radioresistance and enhance preclinical anti‐cancer therapy.

Bioconjugated gold nanoparticles as a molecular based contrast agent: implications for imaging of deep tumors using optoacoustic tomography

Optoacoustic tomography (OAT) is a novel medical imaging method that uses optical illumination and ultrasonic detection to produce deep tissue images based on their light absorption. Abnormal angiogenesis in advanced tumors, that increases the blood content of the tumor, is an endogenous contrast agent for OAT. In early stages, however, angiogenesis is not sufficient to differentiate a tumor from normal tissue; justifying the application of an exogenous contrast agent. We have developed a molecular based contrast agent composed of gold nanoparticles conjugated to a monoclonal antibody that improves OAT imaging to potentiate its use in imaging deep tumors in early stages of cancer or metastatic lesions. Due to their strong optoacoustic signal, we used gold nanoparticles (NPs) as a contrast agent. To target NPs to breast cancer cells, we conjugated NPs to a monoclonal antibody that specifically binds cell surface receptors known to be overexpressed in human breast tumors. In a series of in vitro experiments, Herceptin (monoclonal antibody that binds HER2/neu) conjugated to 40 nm NPs (Mab/NPs) selectively targeted human SK-BR-3 breast cancer cells. The breast cancer cells were detected and imaged by OAT in a gelatin phantom that optically resembled breast tissue. Sensitivity experiments showed that a concentration as low as 10(9) NPs per ml were detectable at a depth of 6 cm. Experimental data together with theoretical analysis demonstrate the feasibility of detection of deeply seeded small tumors that express tumor associated antigens using targeted gold NPs and OAT.