Deep-tissue photoacoustic imaging at the second near-infrared region using newly synthesized nickel(II) dithioloene-containing polymeric nanoparticles

Extrinsic contrast agents with excellent light absorption properties in the second near-infrared (NIR-II, 1000-1350 nm) region can be a key to enhance the contrast of photoacoustic imaging (PAI) in deep tissues. Here, we demonstrated a photoacoustic (PA) contrast agent at 1064 nm optical wavelength for deep-tissue in vivo PAI. We successfully synthesized nickel(II) dithiolene-based polymeric nanoparticles (NNP) that have strong absorption at NIR-II light and generate improved PA signal with a 1064 nm pulse laser. To confirm the feasibility of the NNP, we have conducted both in vitro and in vivo PA experiments and acquired highly contrast-enhanced PA images. We successfully obtained contrast-enhanced PA images of a tube filled with NNP deeply located below several layers of chicken tissue. The maximum PAI penetration depth was about 5 cm. Next, we performed bladder, sentinel lymph node and gastrointestinal tract, which are clinically important, PAI in rats to confirm that NNP could be utilized as a PA agent in deep tissues in vivo. NNP was injected into each of the three cases, and we confirmed that PA contrast was significantly increased after the injections. These results demonstrate that the enhanced PA signals generated by irradiating 1064 nm laser to NNP in deep-tissue has sufficient contrast for PAI. Based on the excellent absorbability of NNP at 1064 nm and the translability of clinical PAI systems, this study is expected to provide a great opportunity for a variety of studies on non-invasive deep tissue in vivo.

[1]  Chulhong Kim,et al.  A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-rasLA2 mutant mice. , 2019, Cancer research.

[2]  Chulhong Kim,et al.  Synergistic effects of cisplatin chemotherapy and gold nanorod-mediated hyperthermia on ovarian cancer cells and tumors. , 2014, Nanomedicine.

[3]  Chulhong Kim,et al.  Programmable Real-time Clinical Photoacoustic and Ultrasound Imaging System , 2016, Scientific Reports.

[4]  J. Rhie,et al.  Multispectral ex vivo photoacoustic imaging of cutaneous melanoma for better selection of the excision margin , 2018, The British journal of dermatology.

[5]  Chulhong Kim,et al.  Opportunities for Photoacoustic-Guided Drug Delivery. , 2015, Current drug targets.

[6]  Chulhong Kim,et al.  "Smart" gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation. , 2016, Chemical communications.

[7]  Liang Song,et al.  Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging , 2016, Nanoscale Research Letters.

[8]  Chulhong Kim,et al.  In Vivo Photoacoustic Imaging of Livers Using Biodegradable Hyaluronic Acid‐Conjugated Silica Nanoparticles , 2018 .

[9]  Jin Young Kim,et al.  High-speed and high-SNR photoacoustic microscopy based on a galvanometer mirror in non-conducting liquid , 2016, Scientific Reports.

[10]  Chulhong Kim,et al.  Clinical photoacoustic imaging platforms , 2018, Biomedical Engineering Letters.

[11]  Chulhong Kim,et al.  Bi2Se3 nanoplates for contrast-enhanced photoacoustic imaging at 1064 nm. , 2018, Nanoscale.

[12]  P. Prasad,et al.  Surfactant-stripped naphthalocyanines for multimodal tumor theranostics with upconversion guidance cream. , 2017, Nanoscale.

[13]  S. Yun,et al.  Hyaluronate-Gold Nanorod/DR5 Antibody Complex for Noninvasive Theranosis of Skin Cancer. , 2016, ACS applied materials & interfaces.

[14]  Chulhong Kim,et al.  Biodegradable Nitrogen-Doped Carbon Nanodots for Non-Invasive Photoacoustic Imaging and Photothermal Therapy , 2016, Theranostics.

[15]  Chulhong Kim,et al.  Biodegradable Photonic Melanoidin for Theranostic Applications. , 2016, ACS nano.

[16]  Lihong V. Wang,et al.  In vivo photoacoustic tomography of chemicals: high-resolution functional and molecular optical imaging at new depths. , 2010, Chemical reviews.

[17]  Jongbeom Kim,et al.  Super-resolution localization photoacoustic microscopy using intrinsic red blood cells as contrast absorbers , 2019, Light: Science & Applications.

[18]  Chulhong Kim,et al.  Surfactant‐Stripped Micelles for NIR‐II Photoacoustic Imaging through 12 cm of Breast Tissue and Whole Human Breasts , 2019, Advanced materials.

[19]  Jin Young Kim,et al.  Super Wide-Field Photoacoustic Microscopy of Animals and Humans In Vivo , 2020, IEEE Transactions on Medical Imaging.

[20]  Lihong V. Wang,et al.  Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs , 2012, Science.

[21]  Chulhong Kim,et al.  Real-Time Photoacoustic Thermometry Combined With Clinical Ultrasound Imaging and High-Intensity Focused Ultrasound , 2019, IEEE Transactions on Biomedical Engineering.

[22]  Chulhong Kim,et al.  Tumor vasodilation by N-Heterocyclic carbene-based nitric oxide delivery triggered by high-intensity focused ultrasound and enhanced drug homing to tumor sites for anti-cancer therapy. , 2019, Biomaterials.

[23]  Chulhong Kim,et al.  Reflection‐mode switchable subwavelength Bessel‐beam and Gaussian‐beam photoacoustic microscopy in vivo , 2018, Journal of biophotonics.