scholarly journals Bioinspired Long-Wavelength Excitable Near-Infrared AIEdots for Endometriosis Targeting and Image-Guided Surgery

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 ◽  
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>


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Joy L. Kovar ◽  
Lael L. Cheung ◽  
Melanie A. Simpson ◽  
D. Michael Olive

Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds.In vivotargeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy.In vitroandin vivoblocking studies confirmed YC-27 specificity.In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.


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.


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.


Author(s):  
Zhongbing Wu ◽  
Yang Zhao ◽  
Fuyang Yu ◽  
Huijuan Shi ◽  
Jing Li

Background: In recent years, there is an increasing interest in using Traditional Chinese medicine (TCM) and their patents for the treatment of cancers. Qigefang (QGF) is a TCM formula and has been used for the treatment of metastatic esophageal cancer in China. However, its therapeutic effect on tumors and its mechanism of action are largely unknown. The aim of this study is to explore the role of QGF in the treatment of metastasis of esophageal squamous cell carcinoma(ESCC). Methods: Human esophageal carcinoma cell line KYSE150 was used for this study. CCK-8 assay was used to determine the cytotoxicity of QGF. The KYSE150 cells were treated with QGF to determine its effect on cell migration (cell scratch assay and imaging) and invasion (Transwell system based with Matrigel assay). Western blotting was used to investigate the effect of QGF on relevant molecules of signaling pathways. A mouse model of lung metastasis of esophageal cancer was established by injecting the KYSE150-Luc cells through the tail vein. Small animal imaging system was used to observe tumor metastasis in the mice. Results: QGF reduced cell migration and invasion of KYSE150 cells. QGF significantly inhibited lung metastasis in nude mice. Further study revealed that the expression of Growth arrest-specific 6 (Gas6), Anexelekto (Axl), N-nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) proteins were decreased both in vitro and in vivo upon treatment with QGF. Conclusion: QGF could prevent invasion and metastasis of esophageal cancer by inhibiting the Gas6/Axl signaling pathway


2018 ◽  
Vol 50 (2) ◽  
pp. 569-584 ◽  
Author(s):  
Mingrong Cheng ◽  
Daxi Ma ◽  
Kangkang Zhi ◽  
Baochi  Liu ◽  
Weiping Zhu

Background/Aims: Our previous study found that a nanoparticle drug delivery system that operates as a drug carrier and controlled release system not only improves the efficacy of the drugs but also reduces their side effects. However, this system could not efficiently target hepatoma cells. The aim of this study was to synthesize biotin-modified galactosylated chitosan nanoparticles (Bio-GC) and evaluate their characteristics in vitro and in vivo. Methods: Bio-GC nanomaterials were synthesized, and confirmed by fourier transform infrared spectroscopy (FT-IR) and hydrogen-1 nuclear magnetic resonance (1H-NMR). The liver position and cancer target property of Bio-GC nanoparticles in vitro and in vivo was tested by confocal laser and small animal imaging system. The characteristics of Bio-GC/5-fluorouracil (5-FU) nanoparticles in vitro and in vivo were explored by cell proliferation, migration and cytotoxicity test, or by animal experiment. Results: Bio-GC nanoparticles were synthesized with biodegradable chitosan as the nanomaterial skeleton with biotin and galactose grafts. Bio-GC was confirmed by FT-IR and 1H-NMR. Bio-GC/5-FU nanoparticles were synthesized according to the optimal mass ratio for Bio-GC/5-FU (1: 4) and had a mean particle size of 81.1 nm, zeta potential of +39.2 mV, and drug loading capacity of 8.98%. Bio-GC/5-FU nanoparticles had sustained release properties (rapid, steady, and slow release phases). Bio-GC nanoparticles targeted liver and liver cancer cell in vitro and in vivo, and this was confirmed by confocal laser scanning and small animal imaging system. Compared with GC/5-FU nanoparticles, Bio-GC/5-FU nanoparticles showed more specific cytotoxic activity in a dose- and time-dependent manner and a more obvious inhibitory effect on the migration of liver cancer cells. In addition, Bio-GC/5-FU nanoparticles significantly prolonged the survival time of mice in orthotopic liver cancer transplantation model compared with other 5-FU nanoparticles or 5-FU alone. Bio-GC (0.64%) nanomaterial had no obvious cytotoxic effects on cells; thus, the concentration of Bio-GC/5-FU nanoparticles used was only 0.04% and showed no toxic effects on the cells. Conclusion: Bio-GC is a liver- and cancer-targeting nanomaterial. Bio-GC/5-FU nanoparticles as drug carriers have stronger inhibitory effects on the proliferation and migration of liver cancer cells compared with 5-FU in vitro and in vivo.


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 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.


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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