Upconversion Luminescence Imaging of Tumors with EGFR-Affibody Conjugated Nanophosphors

MRS Advances ◽  
2019 ◽  
Vol 4 (46-47) ◽  
pp. 2461-2470 ◽  
Author(s):  
Majid Badieirostami ◽  
Colin Carpenter ◽  
Guillem Pratx ◽  
Lei Xing ◽  
Conroy Sun

ABSTRACTNear infrared (NIR) optical imaging has demonstrated significant potential as an effective modality for cancer molecular imaging. Among various NIR probes currently under investigation, upconversion nanophosphors (UCNPs) possess great promise due to their anti-Stokes emission and sequential photon absorption which result in superior detection sensitivity and a simple imaging setup, respectively. Here we investigated the utility of this imaging modality to detect tumor cells expressing the epidermal growth factor receptor (EGFR) using affibody functionalized nanophosphors and a custom built imaging system. Initially, aqueous dispersible NaYF4: Tm+3, Yb+3 UCNPs were synthesized and their photophysical properties were characterized. Then, their luminescence response as a function of concentration and their depth resolving capability in a tissue-simulating phantom were examined. Finally, we demonstrated the use of bioconjugated UCNPs for imaging EGFR-expressing tumors both in vitro and in vivo. Our data suggests that NIR imaging with UCNPs may be useful for noninvasive imaging of tumors.

1999 ◽  
Vol 50 (5) ◽  
pp. 881 ◽  
Author(s):  
D. J. Farrell

The focus of this paper is on the energy evaluation of foodstuffs, particularly of food grains for poultry. Apparent metabolisable energy (AME) is currently the preferred feeding system for poultry but net energy systems are future possibilities and one is currently being used in some poultry growth models. These systems take into account the efficiency with which AME is being utilised by the bird. Aspects such as AME adjusted to zero nitrogen retention and true metabolisable energy (TME) are discussed. Shortcomings of the AME system are also discussed and recent net energy systems are described briefly. The in vitro prediction of AME or TME has not shown great promise although the European Tables of Energy Values for Foodstuffs contain detailed analysis of chemical composition and AMEn data allowing improved accuracy of prediction. It is suggested that data generated on Australian grains should be tested using these tables, and if successful, these tables may be useful to industry. Near infrared reflectance analysis (NIRA) is likely to be the preferred in vitro method for predicting a range of characteristics of food grains including AME. A new method of grain evaluation developed in Canada is described and this approach, with modification, may be worth pursuing in Australia. For the in vivo method of measuring AME of grains, the classical total collection method with broiler chickens is recommended with minor changes. The use of acid-insoluble ash for estimating dry matter digestibility for subsequent determination of AME may have merit. A rapid assay appropriate to laying hens is proposed because of the known increase in AME of grains as birds age. It has been established that AME values generated using adult cockerels also apply reasonably well to hens.


2021 ◽  
Vol 9 ◽  
Author(s):  
Sijia Feng ◽  
Huizhu Li ◽  
Chang Liu ◽  
Mo Chen ◽  
Huaixuan Sheng ◽  
...  

Treatment according to the dynamic changes of bacterial load in vivo is critical for preventing progression of bacterial infections. Here, we present a lead sulfide quantum dots (PbS QDs) based second near-infrared (NIR-II) fluorescence imaging strategy for bacteria detection and real-time in vivo monitoring. Four strains of bacteria were labeled with synthesized PbS QDs which showed high bacteria labeling efficiency in vitro. Then bacteria at different concentrations were injected subcutaneously on the back of male nude mice for in vivo imaging. A series of NIR-II images taken at a predetermined time manner demonstrated changing patterns of photoluminescence (PL) intensity of infected sites, dynamically imaging a changing bacterial load in real-time. A detection limit around 102–104 CFU/ml was also achieved in vivo. Furthermore, analysis of pathology of infected sites were performed, which showed high biocompatibility of PbS QDs. Therefore, under the guidance of our developed NIR-II imaging system, real-time detection and spatiotemporal monitoring of bacterial infection in vivo can be achieved, thus facilitating anti-infection treatment under the guidance of the dynamic imaging of bacterial load in future.


2021 ◽  
Author(s):  
Huashan Zhao ◽  
Chunbin Li ◽  
Wen Zhu ◽  
Ming Yu ◽  
Binbin Huang ◽  
...  

Endometriosis(EM)is a non-cancerous and intractable disease in clinic due to the ambiguity of its etiology and mechanism. Surgical removal of the lesions is more efficient method for EM treatment compared with pharmacological intervention. Intraoperative identification of the endometrial ectopic sites is a prerequisite, however, available probes with high specificity remain limited, owing to lack of specific biomarkers. Here, based on a polypeptide derived from VAR2CSA protein (CSA) and a near-infrared AIE material (TPA-TBZ-2), we prepared a CSA AIEdots capable of labeling the EM lesions by a one-step nanoprecipitation method. The nanodots have an absorbance maximum at 610 nm with a wide emission range from 650 to 850 nm and an absolute quantum yield of up to 34% in the aggregation states. Through in vitro assay, the dots could specifically label endometrioid cells (Ishikawa cells), and flow cytometry experiments showed its specific spectral absorption peak, compared with empty particles and scrambled peptide groups. Next, to verify the ability of the dots to label the ectopic endometrium in vivo, we established a mouse model of endometriosis. After injection the dots into model mouse intravenously for 24 hours, the AIE signaling could be specifically detected at the ectopic lesions in an IVIS small animal imaging system. The CSA AIEdots were further used for image-guided EM resection in vivo and showed a high EM-to-normal tissue signal ratio. Taken together, our AIE nanodots-based EM diagnosis system is a promising candidate for EM development monitoring and surgical navigations. <br>


2017 ◽  
Vol 1 (S1) ◽  
pp. 9-9
Author(s):  
Adam Grippin ◽  
Elias Sayour ◽  
Jon Dobson ◽  
Duane A. Mitchell

OBJECTIVES/SPECIFIC AIMS: Immune-based therapies hold great promise for treatment of refractory tumors. However, development is limited by a lack of identified immune correlates to vaccination. We recently showed that dendritic cells (DCs) prolong progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, and that DC migration to site draining lymph nodes robustly correlates with both PFS and OS. While this appears to be a reliable immune correlate, the complexity of routine labeling for PET and SPECT prohibits validation in a large clinical study. We therefore seek to develop a safe, translatable reporter that can be imaged with a widely available imaging modality. METHODS/STUDY POPULATION: The cationic liposome 1,2-doleoyl-3-trimethylammonium-propane (DOTAP) was loaded with MRI-imageable iron oxide nanoparticles (IONPs) with or without the neutral molecules PEG and cholesterol. The resulting nanoparticles were loaded with RNA to form RNA-NPs that were characterized with transmission electron microscopy (TEM) and used to transfect DCs in vitro; 4.7 T MRI was then used to image particles or cells in agarose gel phantoms. RESULTS/ANTICIPATED RESULTS: TEM images of RNA-NPs indicate the presence of IONP-loaded liposomes. In vitro transfection experiments demonstrate that iron oxide does not reduce RNA-NP-mediated transfection of DCs. Additionally, small amounts of either PEG or cholesterol within RNA-NPs increased transfection of DC2.4s and enhanced T-cell priming by bone marrow-derived dendritic cells. A series of 4.7 T MRI images of particles in cells, spleens, and LNs demonstrated quantifiable differences in particle density between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that IONP-loaded RNA-NPs can be imaged with MRI and manipulated to augment DC function. Future work will include in vivo imaging in mice and safety studies to facilitate translation into first-in-human studies. Successful completion of this project would provide a powerful clinical tool to improve and track patient responses to immune therapy.


Author(s):  
Anthony J. Durkin ◽  
Jae G. Kim ◽  
David J. Cuccia

We present a wide-field, near infrared spectral imaging modality called modulated imaging (MI) that shows great promise for quantitatively imaging superficial (1–5 mm depth) tissues. We have applied this method to a dorsal pedicle skin flap model to determine in-vivo local concentrations of oxy- and deoxy-hemoglobin and water.


Author(s):  
Philippa Meershoek ◽  
Gijs H. KleinJan ◽  
Danny M. van Willigen ◽  
Kevin P. Bauwens ◽  
Silvia J. Spa ◽  
...  

AbstractThe field of fluorescence-guided surgery builds on colored fluorescent tracers that have become available for different clinical applications. Combined use of complementary fluorescent emissions can allow visualization of different anatomical structures (e.g. tumor, lymphatics and nerves) in the same patient. With the aim to assess the requirements for multi-color fluorescence guidance under in vivo conditions, we thoroughly characterized two FDA-approved laparoscopic Firefly camera systems available on the da Vinci Si or da Vinci Xi surgical robot. In this process, we studied the cameras’ performance with respect to the photophysical properties of the FDA-approved dyes Fluorescein and ICG. Our findings indicate that multi-wavelength fluorescence imaging of Fluorescein and ICG is possible using clinical-grade fluorescence laparoscopes, but critical factors for success include the photophysical dye properties, imaging system performance and the amount of accumulated dye. When comparing the camera performance, the Xi system provided more effective excitation (adaptions in the light source) and higher detection sensitivity (chip-on-a-tip and/or enhanced image processing) for both Fluorescein and ICG. Both systems can readily be used for multi-wavelength fluorescence imaging of Fluorescein and ICG under clinically relevant conditions. With that, another step has been made towards the routine implementation of multi-wavelength image-guided surgery concepts.


2021 ◽  
Author(s):  
Huashan Zhao ◽  
Chunbin Li ◽  
Wen Zhu ◽  
Ming Yu ◽  
Binbin Huang ◽  
...  

Endometriosis(EM)is a non-cancerous and intractable disease in clinic due to the ambiguity of its etiology and mechanism. Surgical removal of the lesions is more efficient method for EM treatment compared with pharmacological intervention. Intraoperative identification of the endometrial ectopic sites is a prerequisite, however, available probes with high specificity remain limited, owing to lack of specific biomarkers. Here, based on a polypeptide derived from VAR2CSA protein (CSA) and a near-infrared AIE material (TPA-TBZ-2), we prepared a CSA AIEdots capable of labeling the EM lesions by a one-step nanoprecipitation method. The nanodots have an absorbance maximum at 610 nm with a wide emission range from 650 to 850 nm and an absolute quantum yield of up to 34% in the aggregation states. Through in vitro assay, the dots could specifically label endometrioid cells (Ishikawa cells), and flow cytometry experiments showed its specific spectral absorption peak, compared with empty particles and scrambled peptide groups. Next, to verify the ability of the dots to label the ectopic endometrium in vivo, we established a mouse model of endometriosis. After injection the dots into model mouse intravenously for 24 hours, the AIE signaling could be specifically detected at the ectopic lesions in an IVIS small animal imaging system. The CSA AIEdots were further used for image-guided EM resection in vivo and showed a high EM-to-normal tissue signal ratio. Taken together, our AIE nanodots-based EM diagnosis system is a promising candidate for EM development monitoring and surgical navigations. <br>


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vu Hoang Minh Doan ◽  
Van Tu Nguyen ◽  
Sudip Mondal ◽  
Thi Mai Thien Vo ◽  
Cao Duong Ly ◽  
...  

AbstractImaging modalities combined with a multimodal nanocomposite contrast agent hold great potential for significant contributions in the biomedical field. Among modern imaging techniques, photoacoustic (PA) and fluorescence (FL) imaging gained much attention due to their non-invasive feature and the mutually supportive characteristic in terms of spatial resolution, penetration depth, imaging sensitivity, and speed. In this present study, we synthesized IR783 conjugated chitosan–polypyrrole nanocomposites (IR-CS–PPy NCs) as a theragnostic agent used for FL/PA dual-modal imaging. A customized FL and photoacoustic imaging system was constructed to perform required imaging experiments and create high-contrast images. The proposed nanocomposites were confirmed to have great biosafety, essentially a near-infrared (NIR) absorbance property with enhanced photostability. The in vitro photothermal results indicate the high-efficiency MDA-MB-231 breast cancer cell ablation ability of IR-CS–PPy NCs under 808 nm NIR laser irradiation. The in vivo PTT study revealed the complete destruction of the tumor tissues with IR-CS–PPy NCs without further recurrence. The in vitro and in vivo results suggest that the demonstrated nanocomposites, together with the proposed imaging systems could be an effective theragnostic agent for imaging-guided cancer treatment.


Author(s):  
E. D. Salmon ◽  
J. C. Waters ◽  
C. Waterman-Storer

We have developed a multi-mode digital imaging system which acquires images with a cooled CCD camera (Figure 1). A multiple band pass dichromatic mirror and robotically controlled filter wheels provide wavelength selection for epi-fluorescence. Shutters select illumination either by epi-fluorescence or by transmitted light for phase contrast or DIC. Many of our experiments involve investigations of spindle assembly dynamics and chromosome movements in live cells or unfixed reconstituted preparations in vitro in which photodamage and phototoxicity are major concerns. As a consequence, a major factor in the design was optical efficiency: achieving the highest image quality with the least number of illumination photons. This principle applies to both epi-fluorescence and transmitted light imaging modes. In living cells and extracts, microtubules are visualized using X-rhodamine labeled tubulin. Photoactivation of C2CF-fluorescein labeled tubulin is used to locally mark microtubules in studies of microtubule dynamics and translocation. Chromosomes are labeled with DAPI or Hoechst DNA intercalating dyes.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yipengchen Yin ◽  
Yongjing Li ◽  
Sheng Wang ◽  
Ziliang Dong ◽  
Chao Liang ◽  
...  

Abstract Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.


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