NIR-II nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer

Abstract

Local recurrence is a common cause of treatment failure for patients with solid tumors. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and, thereby improve prognosis. Here, we report in vivo assembly of the second near-infrared window (NIR-II) emitting downconversion nanoparticles (DCNPs) modified with DNA and targeting peptides to improve the image-guided surgery for metastatic ovarian cancer. The NIR-II imaging quality with DCNPs is superior to that of clinically approved ICG with good photostability and deep tissue penetration (8 mm). Stable tumor retention period experienced 6 h by in vivo assembly of nanoprobes can be used for precise tumor resection. Superior tumor-to-normal tissue ratio is successfully achieved to facilitate the abdominal ovarian metastases surgical delineation. Metastases with ≤1 mm can be completely excised under NIR-II bioimaging guidance. This novel technology provides a general new basis for the future design of nanomaterials for medical applications.

Excretable Lanthanide Nanoparticle for Biomedical Imaging and Surgical Navigation in the Second Near‐Infrared Window

“…[1][2][3][4] Therefore, it requires effective imaging tools to assess the progression of diseases and their therapeutic response. [7][8][9][10][11] To date, compared to fluorescence imaging in the visible and nearinfrared wavelengths (<900 nm), deep tissue imaging in the second near-infrared window (NIR-II, 1000-1700 nm) has benefited from negligible tissue autofluorescence and scattering, leading to superior improvements in higher resolution and fidelity. [5,6] As a promising candidate of imaging modality with respect to noninvasive and nonradiation, optical imaging has been an area of intense focus in real-time visualization and monitoring the dynamic pathological processes of diseases.…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…Traditional LN mapping techniques in clinical applications include radionuclide, blue dyes, and fluorescence imaging. 2019, 31,1904329 Passive targeting via EPR effect -PDFT1032 LN mapping and biopsy, osteosarcoma imaging and IGS [31] -SNPs LN mapping [32] -PDI NPs LN mapping and biopsy, glioblastoma imaging and PTT guidance [33] -AGL AIE dots Peritoneal carcinomatosis imaging and IGS [34] -HLZ-BTED dots Breast tumor imaging and visualizing tumor feeding blood vessels [35] -L897 NPs LN and glioblastoma imaging [36] -BPN-BBTD NPs Bladder tumor imaging and PTT guidance [37] Active targeting via ligands Peptide FSH β receptor DCNP-L 1 -FSH β Ovarian cancer imaging and IGS [38] Integrin α v β 3 IR-BEMC6P@RGD Gastroenteropancreatic neuroendocrine tumor imaging and IGS [39] T-TTD dots a) Cholangiocarcinoma imaging and PDT guidance [40] T-TPETS nanodots b) Hepatocellular carcinoma, imaging and PDT guidance [41] 68 Indocyanine green (ICG) is the only near-infrared fluorescence (NIRF) agent approved for clinical application by the Food and Drug Administration (FDA); it is widely used in ophthalmic angiography, the measurement of circulatory system and liver functions, and studies on intraoperative tumor imaging and LN mapping for various cancers, such as head and neck, [59] breast, [60] lung, gastrointestinal, [61] and urologic cancer. [55,56] The combination of two methods with a radionuclide and a dye has been the gold standard for SLN detection.…”

“…[94] Peptides are among the most popular targeting ligands due to their rapid clearance, high affinities, and specificities for their targets. [38,39,96] Wang et al reported an in vivo assembling downconversion NP (DCNP) modified with DNA (L 1 ) and follicle-stimulating hormone (FSH β ) peptide (called DCNP-L 1 -FSH β ). [38,39,96] Wang et al reported an in vivo assembling downconversion NP (DCNP) modified with DNA (L 1 ) and follicle-stimulating hormone (FSH β ) peptide (called DCNP-L 1 -FSH β ).…”

“…[38,39,96] Wang et al reported an in vivo assembling downconversion NP (DCNP) modified with DNA (L 1 ) and follicle-stimulating hormone (FSH β ) peptide (called DCNP-L 1 -FSH β ). [38] After two-staged sequential intravenous injections, DCNP-L 1 -FSH β achieved stable retention in tumors and superior T/NT ratio from 20 to 26 h PI, with an ≈6 h optimal surgical time window (Figure 3b-e). [38] After two-staged sequential intravenous injections, DCNP-L 1 -FSH β achieved stable retention in tumors and superior T/NT ratio from 20 to 26 h PI, with an ≈6 h optimal surgical time window (Figure 3b-e).…”

“…[109][110][111][112][113] However, the clinical application of novel optical imaging techniques faces various challenges, as well as requirements for optimal nanoprobes, as follows: 1) deep tissue penetration and high brightness; 2) high SBR or T/NT ratio to recognize tumors correctly Adv. [38] Copyright 2018, Springer Nature. 2019, 31,1904329 in vivo assembly of DCNP-L 1 -FSH β (first injection) and DCNP-L 2 -FSH β (second injection) with improved tumor targeting and rapid hepatic and renal clearance after two stages in sequence injections.…”