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Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection.

ABSTRACT: Near infrared (NIR) fluorescence imaging (700-900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further self-assembly between an amphiphilic block co-polymer and the obtained AIE molecules leads to AIE nanoparticles (AIE NPs), which have absorption maxima at 635 nm and emission maxima between 800 and 815 nm with quantum yields of up to 4.8% in aggregated states. In vitro and in vivo toxicity results demonstrate that the synthesized AIE NPs are biocompatible. Finally, the synthesized AIE NPs have been successfully used for image-guided tumor resection with a high tumor-to-normal tissue signal ratio of 7.2.

SUBMITTER: Liu J

PROVIDER: S-EPMC5426438 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection.

Liu Jie J Chen Chao C Ji Shenglu S Liu Qian Q Ding Dan D Zhao Dan D Liu Bin B

Chemical science 20170120 4

Near infrared (NIR) fluorescence imaging (700-900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further s ...[more]

PMID: 28553514

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Project description:Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient. In order to remove the tumor tissue completely with minimal collateral damage to healthy tissue, there is a need for diagnostic tools that will differentiate between the tumor and its normal surroundings. Methods: We designed, synthesized and characterized three novel polymeric Turn-ON probes that will be activated at the tumor site by cysteine cathepsins that are highly expressed in multiple tumor types. Utilizing orthotopic breast cancer and melanoma models, which spontaneously metastasize to the brain, we studied the kinetics of our polymeric Turn-ON nano-probes. Results: To date, numerous low molecular weight cathepsin-sensitive substrates have been reported, however, most of them suffer from rapid clearance and reduced signal shortly after administration. Here, we show an improved tumor-to-background ratio upon activation of our Turn-ON probes by cathepsins. The signal obtained from the tumor was stable and delineated the tumor boundaries during the whole surgical procedure, enabling accurate resection. Conclusions: Our findings show that the control groups of tumor-bearing mice, which underwent either standard surgery under white light only or under the fluorescence guidance of the commercially-available imaging agents ProSense® 680 or 5-aminolevulinic acid (5-ALA), survived for less time and suffered from tumor recurrence earlier than the group that underwent image-guided surgery (IGS) using our Turn-ON probes. Our "smart" polymeric probes can potentially assist surgeons' decision in real-time during surgery regarding the tumor margins needed to be removed, leading to improved patient outcome.

Project description:ObjectivesNear-infrared fluorescent imaging has been described for intraoperative mapping of the draining lymph nodes in human cancer and canine oral tumours. The aim of this study was to retrospectively describe the results of lymphadenectomies in dogs with mast cell tumours treated either by standard unguided locoregional lymph node dissection or near-infrared fluorescent image-guided lymph node dissection.MethodsMedical records between 2012 and 2020 were reviewed for dogs that were presented for surgical resection of mast cell tumours with concurrent lymphadenectomy either with (near-infrared fluorescent image-guided lymph node dissection) or without near-infrared fluorescence image guidance (lymph node dissection). The number and location of lymph nodes planned for surgical dissection and actually dissected nodes, presence of metastases and perioperative complications were recorded.ResultsThirty-five patients underwent near-infrared fluorescent image-guided lymph node dissection, and 43 lymph node dissections. The number of nodes preoperatively planned for resection were 70 and 68, respectively. Fifty-eight of those (83%) were identified during near-infrared fluorescent image-guided lymph node dissection procedures, compared with 50 (74%) during lymph node dissection. near-infrared fluorescent image-guided lymph node dissection resulted in resection of additional fluorescent nodes not corresponding to locoregional nodes in 15 of 35 dogs. Using near-infrared fluorescent image-guided lymph node dissection, we identified at least one metastatic node in 68% of dogs (24 of 35) compared with 33% (14 of 43) when lymph node dissection was used without imaging. No complications related to near-infrared fluorescent imaging were reported.Clinical significanceThe present study suggests that near-infrared imaging is a promising technique for intraoperative detection of the draining lymph nodes in dogs with mast cell tumours. Further validation of the technique is required to assess if near-infrared fluorescent imaging can detect the true sentinel lymph node.

Dataset Information

Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection.

Publications

Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection.

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