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Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

ABSTRACT: Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5?-cholanamide (5?CA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone.

SUBMITTER: Hill TK

PROVIDER: S-EPMC4373659 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

Hill Tanner K TK Abdulahad Asem A Kelkar Sneha S SS Marini Frank C FC Long Timothy E TE Provenzale James M JM Mohs Aaron M AM

Bioconjugate chemistry 20150116 2

Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye t ...[more]

PMID: 25565445

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Project description:Background: Indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) has been recently adopted in pediatric minimally invasive surgery (MIS). This study aimed to report our experience with ICG-guided NIRF in pediatric laparoscopy and robotics and evaluate its usefulness and technique of application in different pediatric pathologies. Methods: ICG technology was adopted in 76 laparoscopic and/or robotic procedures accomplished in a single division of pediatric surgery over a 24-month period (January 2018-2020): 40 (37 laparoscopic, three robotic) left varicocelectomies with intra-operative lymphography; 13 (10 laparoscopic, three robotic) renal procedures: seven partial nephrectomies, three nephrectomies, and three renal cyst deroofings; 12 laparoscopic cholecystectomies; five robotic tumor excisions; three laparoscopic abdominal lymphoma excisions; three thoracoscopic procedures: two lobectomies and one lymph node biopsy for suspected lymphoma. The ICG solution was administered into a peripheral vein in all indications except for varicocele and lymphoma in which it was, respectively, injected into the testis body or the target organ. Regarding the timing of the administration, the ICG solution was administered intra-operatively in all indications except for cholecystectomy in which the ICG injection was performed 15-18 h before surgery. Results: No conversions to open or laparoscopy occurred. No adverse and allergic reactions to ICG or other postoperative complications were reported. Conclusions: Based upon our 2 year experience, we believe that ICG-guided NIRF is a very useful tool in pediatric MIS to perform a true imaged-guided surgery, allowing an easier identification of anatomic structures and an easier surgical performance in difficult cases. The most common applications in pediatric surgery include varicocele repair, difficult cholecystectomy, partial nephrectomy, lymphoma, and tumors excision but further indications will be soon discovered. ICG-enhanced fluorescence was technically easy to apply and safe for the patient reporting no adverse reactions to the product. The main limitation is represented by the specific equipment needed to apply ICG-guided NIRF in laparoscopic procedures, that is not available in all centers whereas the ICG system Firefly® is already integrated into the robotic platform.

Project description:Phototherapy is a light-triggered treatment for tumor ablation and growth inhibition via photodynamic therapy (PDT) and photothermal therapy (PTT). Despite extensive studies in this area, a major challenge is the lack of selective and effective phototherapy agents that can specifically accumulate in tumors to reach a therapeutic concentration. Although recent attempts have produced photosensitizers complexed with photothermal nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy still hampers the broad utilization of these nanocarriers. Herein, we developed a CD44 targeted photoacoustic (PA) nanophototherapy agent by conjugating Indocyanine Green (ICG) to hyaluronic acid nanoparticles (HANPs) encapsulated with single-walled carbon nanotubes (SWCNTs), resulting in a theranostic nanocomplex of ICG-HANP/SWCNTs (IHANPT). We fully characterized its physical features as well as PA imaging and photothermal and photodynamic therapy properties in vitro and in vivo. Systemic delivery of IHANPT theranostic nanoparticles led to the accumulation of the targeted nanoparticles in tumors in a human cancer xenograft model in nude mice. PA imaging confirmed targeted delivery of the IHANPT nanoparticles into tumors (T/M ratio = 5.19 ± 0.3). The effect of phototherapy was demonstrated by low-power laser irradiation (808 nm, 0.8 W/cm(2)) to induce efficient photodynamic effect from ICG dye. The photothermal effect from the ICG and SWCNTs rapidly raised the tumor temperature to 55.4 ± 1.8 °C. As the result, significant tumor growth inhibition and marked induction of tumor cell death and necrosis were observed in the tumors in the tumors. There were no apparent systemic and local toxic effects found in the mice. The dynamic thermal stability of IHANPT was studied to ensure that PTT does not affect ICG-dependent PDT in phototherapy. Therefore, our results highlight imaging property and therapeutic effect of the novel IHANPT theranostic nanoparticle for CD44 targeted and PA image-guided dual PTT and PDT cancer therapy.

Project description:SIGNIFICANCE:Expanded use of fluorescence-guided surgery with devices approved for use with indocyanine green (ICG) has led to a range of commercial systems available. There is a compelling need to be able to independently characterize system performance and allow for cross-system comparisons. AIM:The goal of this work is to expand on previous proposed fluorescence imaging standard designs to develop a long-term stable phantom that spectrally matches ICG characteristics and utilizes 3D printing technology for incorporating tissue-equivalent materials. APPROACH:A batch of test targets was created to assess ICG concentration sensitivity in the 0.3- to 1000-nM range, tissue-equivalent depth sensitivity down to 6 mm, and spatial resolution with a USAF test chart. Comparisons were completed with a range of systems that have significantly different imaging capabilities and applications, including the Li-Cor® Odyssey, Li-Cor® Pearl, PerkinElmer® Solaris, and Stryker® Spy Elite. RESULTS:Imaging of the ICG-matching phantoms with all four commercially available systems showed the ability to benchmark system performance and allow for cross-system comparisons. The fluorescence tests were able to assess differences in the detectable concentrations of ICG with sensitivity differences >10× for preclinical and clinical systems. Furthermore, the tests successfully assessed system differences in the depth-signal decay rate, as well as resolution performance and image artifacts. The manufacturing variations, photostability, and mechanical design of the tests showed promise in providing long-term stable standards for fluorescence imaging. CONCLUSIONS:The presented ICG-matching phantom provides a major step toward standardizing performance characterization and cross-system comparisons for devices approved for use with ICG. The developed hybrid manufacturing platform can incorporate long-term stable fluorescing agents with 3D printed tissue-equivalent material. Further, long-term testing of the phantom and refinements to the manufacturing process are necessary for future implementation as a widely adopted fluorescence imaging standard.

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Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

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Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

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