Abstract: Sentinel lymph node (SLN) mapping and tumor-boundary delineation play a key role in cancer surgery, as they have great potential to reduce surgical intervention and increase relapse-free survival rates of patients. The autofluorescence imaging (AFI) method can improve the efficiency of tumor delineation and optimize the scope of surgical intervention, but there are still no fluorescent drugs that can be used with such a method to form a hybrid imaging technique. Another problem is bleaching when fluorescent dyes are conjugated with folic acid. This study reports, for the first time, nanosensors with excellent photostability and compatibility with endoscopes for AFI, which makes simultaneous hybrid imaging possible. After functionalization of the quantum dot (QD) surfaces, we found that they bound effectively to MCF-7 cancer cells. The diagnostic value of simultaneous hybrid imaging using common AFI equipment in delineating tumor boundaries and mapping SLN can reduce the cost of diagnosis and increase its reliability.

一种光稳定性优异的叶酸纳米传感器在混合成像中的应用

[1]AhnJY, JungHY, ChoiKD, et al., 2011. Endoscopic and oncologic outcomes after endoscopic resection for early gastric cancer: 1370 cases of absolute and extended indications. Gastrointest Endosc, 74(3):485-493.

[2]AugustineR, MamunAA, HasanA, et al., 2021. Imaging cancer cells with nanostructures: prospects of nanotechnology driven non-invasive cancer diagnosis. Adv Colloid Interface Sci, 294:102457.

[3]BonenkampJJ, HermansJ, SasakoM, et al., 1999. Extended lymph-node dissection for gastric cancer. N Engl J Med, 340(12):908-914.

[4]BrayF, FerlayJ, SoerjomataramI, et al., 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6):394-424.

[5]CummingsD, WongJ, PalmR, et al., 2021. Epidemiology, diagnosis, staging and multimodal therapy of esophageal and gastric tumors. Cancers, 13(3):582.

[6]CuschieriA, WeedenS, FieldingJ, et al., 1999. Patient survival after D₁ and D₂ resections for gastric cancer: long-term results of the MRC randomized surgical trial. Br J Cancer, 79(9):1522-1530.

[7]DegiuliM, SasakoM, PontiA, 2010. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg, 97(5):643-649.

[8]HashemzadehA, AmerizadehF, AsgharzadehF, et al., 2021. Delivery of oxaliplatin to colorectal cancer cells by folate-targeted UiO-66-NH₂. Toxicol Appl Pharmacol, 423:115573.

[9]HeMF, JiangZW, WangCG, et al., 2018. Diagnostic value of near-infrared or fluorescent indocyanine green guided sentinel lymph node mapping in gastric cancer: a systematic review and meta-analysis. J Surg Oncol, 118(8):‍1243-1256.

[10]HokimotoN, SugimotoT, NamikawaT, et al., 2018. A novel color fluorescence navigation system for intraoperative transcutaneous lymphatic mapping and resection of sentinel lymph nodes in breast cancer: comparison with the combination of gamma probe scanning and visible dye methods. Oncology, 94(2):99-106.

[11]HuangL, LiZJ, ZhaoY, et al., 2016. Ultralow-power near infrared lamp light operable targeted organic nanoparticle photodynamic therapy. J Am Chem Soc, 138(44):‍14586-14591.

[12]JiaoY, SunHY, JiaYC, et al., 2019. Functionalized fluorescent carbon nanoparticles for sensitively targeted of folate-receptor-positive cancer cells. Microchem J, 146:464-470.

[13]JungMK, ChoM, RohCK, et al., 2021. Assessment of diagnostic value of fluorescent lymphography-guided lymphadenectomy for gastric cancer. Gastric Cancer, 24(2):515-525.

[14]KelderhouseLE, ChelvamV, WayuaC, et al., 2013. Development of tumor-targeted near infrared probes for fluorescence guided surgery. Bioconjugate Chem, 24(6):‍‍1075-1080.

[15]KimDW, JeongB, ShinIH, et al., 2019. Sentinel node navigation surgery using near-infrared indocyanine green fluorescence in early gastric cancer. Surg Endosc, 33(4):1235-‍1243.

[16]KumarSSD, MaheshA, AntonirajMG, et al., 2018. Cellular imaging and folate receptor targeting delivery of gum kondagogu capped gold nanoparticles in cancer cells. Int J Biol Macromol, 109:220-230.

[17]LiangZB, YangYQ, JiaFJ, et al., 2019. Intrathecal delivery of folate conjugated near-infrared quantum dots for targeted in vivo imaging of gliomas in mice brains. ACS Appl Bio Mater, 2(4):1432-1439.

[18]LiuPF, LiuD, LiuYH, et al., 2016. ANTS-anchored Zn-Al-CO₃-LDH particles as fluorescent probe for sensing of folic acid. J Solid State Chem, 241:164-172.

[19]MadajewskiB, ChenF, MaK, et al., 2018. Dual modality imaging of melanoma using clinically-translated ultrasmall silica nanoparticles targeting integrin and melanocortin-1 receptor expressing melanoma models. J Nucl Med, 59(S1):196.

[20]MatsuiR, InakiN, TsujiT, 2021. Diagnosis of advanced gastric cancer using image enhancement and autofluorescence imaging systems. Asian J Endosc Surg, 14(4):700-706.

[21]MoonWK, LinYH, O'LoughlinT, et al., 2003. Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate. Bioconjugate Chem, 14(3):539-545.

[22]PantaloneD, AndreoliF, FusiF, et al., 2007. Multispectral imaging autofluorescence microscopy in colonic and gastric cancer metastatic lymph nodes. Clin Gastroenterol Hepatol, 5(2):230-236.

[23]PotaraM, Nagy-SimonT, FocsanM, et al., 2021. Folate-targeted Pluronic-chitosan nanocapsules loaded with IR780 for near-infrared fluorescence imaging and photothermal-photodynamic therapy of ovarian cancer. Colloids Surf B Biointerfaces, 203:111755.

[24]RawlaP, BarsoukA, 2019. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterol Rev, 14(1):26-38.

[25]RazikNA, Al-BarakatiG, Al-HenetiS, 1990. Powder diffraction data of CdTe_xSe_1-x solid solutions. Powder Diffract, 5(4):206-209.

[26]SakaiH, KawakamiH, TeramuraT, et al., 2021. Folate receptor α increases chemotherapy resistance through stabilizing MDM2 in cooperation with PHB2 that is overcome by MORAb-202 in gastric cancer. Clin Transl Med, 11(6):e454.

[27]SaljoughiH, KhakbazF, MahaniM, 2020. Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging. Photodiagnosis Photodyn Ther, 30:101687.

[28]Shakeri-ZadehA, RezaeyanA, SarikhaniA, et al., 2021. Folate receptor-targeted nanoprobes for molecular imaging of cancer: friend or foe? Nano Today, 39:101173.

[29]SkripkaA, Mendez-GonzalezD, MarinR, et al., 2021. Near infrared bioimaging and biosensing with semiconductor and rare-earth nanoparticles: recent developments in multifunctional nanomaterials. Nanoscale Adv, 3(22):6310-6329.

[30]SongunI, PutterH, KranenbargEMK, et al., 2010. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol, 11(5):439-449.

[31]SungH, FerlayJ, SiegelRL, et al., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249.

[32]TadaK, OdaI, YokoiC, et al., 2011. Pilot study on clinical effectiveness of autofluorescence imaging for early gastric cancer diagnosis by less experienced endoscopists. Diagn Ther Endosc, 2011:419136.

[33]TangH, YangST, YangYF, et al., 2016. Blood clearance, distribution, transformation, excretion, and toxicity of near-infrared quantum dots Ag₂Se in mice. ACS Appl Mater Interfaces, 8(28):17859-17869.

[34]TungCH, LinYH, MoonWK, et al., 2002. A receptor-targeted near-infrared fluorescence probe for in vivo tumor imaging. ChemBioChem, 8(8):784-786. https://doi.‍org/10.1002/1439-7633(20020802)3:‍8<784:‍AID-CBIC784>3.0.CO;2-X

[35]van CutsemE, SagaertX, TopalB, et al., 2016. Gastric cancer. Lancet, 388(10060):2654-2664.

[36]van DamGM, ThemelisG, CraneLMA, et al., 2011. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-‍αtargeting: first in-human results. Nat Med, 17(10):1315-1319.

[37]YanHJ, YouY, LiXJ, et al., 2020. Preparation of RGD peptide/folate acid double-targeted mesoporous silica nanoparticles and its application in human breast cancer MCF-7 cells. Front Pharmacol, 11:898.

[38]YanY, TianJW, HuFR, et al., 2016. A near IR photosensitizer based on self-assembled CdSe quantum dot-aza-BODIPY conjugate coated with poly(ethylene glycol) and folic acid for concurrent fluorescence imaging and photodynamic therapy. RSC Adv, 6(115):113991-113996.

[39]YangC, BrommaK, ChithraniD, 2018. Peptide mediated in vivo tumor targeting of nanoparticles through optimization in single and multilayer in vitro cell models. Cancers, 10(3):84.

[40]ZhangQ, DengSN, LiuJL, et al., 2019. Cancer-targeting graphene quantum dots: fluorescence quantum yields, stability, and cell selectivity. Adv Funct Mater, 29(5):1805860.