Potential applications of single molecule organic fluorescent nanodots in tumor imaging and surgical navigation

单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用 Recently, Zhejiang University Professor Shen Youqing team Zhou beads Yin, Associate Professor and Qingdao University Professor Cong Hailin cooperation in the ACS Nano published a study entitled Tuning the Brightness and Photostability of Organic Dots for Multivalent Targeted Cancer Imaging and Surgery of the magazine paper. Paper reported A dendritic molecule of single fluorescent nanoparticle developed synthetic strategy point , having good fluorescent nanodots tunable optical properties, have potential applications in the field of surgical navigation and fluorescence imaging in vivo . The paper beads Yin Zhou, associate professor corresponding author, Professor Cong Hailin and Wang Kai Qi doctoral as a co-first author of the article. This work was supported by the National Natural Science Foundation of China (No. 21875211, 51603180, 21675091 and 21874078), the National R & D Program (2016YFA0200301), Fundamental Research Funds for (2019FZA4020) Central Universities, Mount Tai in Shandong Province Young Scholars Program (tsqn20161027) funded Shandong Province Science and technology innovation Program (2018CXGC1407), Shandong Province, the focus of R & D programs (2016GGX102028, 2016GGX102039, 2017GGX20111) and Shandong Province innovation leaders Program (No. 168325zhc) of.

Introduction

fluorescent probe optical imaging technology to reveal the internal state of the disease at the cellular and molecular level, for the early detection, diagnosis and image guided surgery for cancer have considerable application prospect. Currently, most commercial fluorophore compound is a small molecule, for example, cyanine dyes, their development and application by photobleaching, low fluorescence quantum yield, non-vivoDisadvantages specific targeting restrictions, adverse drug dynamics. To solve this problem, small molecules of organic fluorophores peryleneimide as the core, the biodegradable lysine repeating unit, prepared a series of precise dendrimer structures fluorescent nanodots (PDI-PLL-G1 ~ G8). The authors found that fluorescence characteristics may be adjusted by adjusting the size of the dendritic nanodots, dendritic nanodots algebraic high hydrophobic dye can be completely buried inside the dendrimer avoid intermolecular aggregation induced fluorescence quenching. Compared to small molecule organic fluorophores, high algebras dendritic nanodots have higher fluorescence intensity, fluorescence quantum yield can be increased by 20 times, and has excellent stability and resistance to photobleaching. Subsequently, the author PDI-PLL-G5, for example, introduction of biotin (Biotin) molecules on the surface of a tumor targeting ligand, a polyvalent verified fluorescent nanodots dendritic target tumor imaging capability. The results are shown in vivo tumors and normal tissues in situ signal ratio (TNR) is about 3, more than 5 days duration, about 17 TNR vitro, tumor and healthy tissue clear demarcation, the image may be directed to the tumor metastasis model mice surgery to provide accurate judgments. Research Highlights herein 1, of the dye to perylene imide nuclear, safe and nontoxic lysine branching units having synthesized a series of precise structure, purity and satisfactory monodisperse property than high dendrimers.

单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
Figure 1: Synthesis and Characterization of precision PDI-PLL-G0 ~ 8 of the

2, the optical properties of PDI-PLL dendrimer having a size dependent, fluorescence quantum yield increases as the size, increase of about 30 times the life of the optical light stability and an aqueous solution showed a trend of increased with increasing size. Compared to small organic molecule fluorescent dye Cy5, PDI-PLL dendron more long-term ability of the Tracking fluorescence imaging at the cellular level and the level of a living body.

单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
Figure 2: Size-dependent fluorescence intensity PDI-PLL dendrimers and light stability

3, the surface modification on the targeting ability of dendritic fluorescent probe , blood clearance kinetics and biodistribution. Compared to unmodified G5-Ac, the introduction of LC-Biotin ligands did not increase PDI-PLL-G5 uptake and tumor targeting ability receptor-positive cell lines, but accelerated renal clearance. Introducing a multivalent PEG-Biotin can be improved PDI-PLL-G5 receptor positive cell lines of tumor uptake and targeting ability, and the effect of multivalent ligand binding to the receptor better than monovalent, as the number of ligands increased cellular uptake was significantly improved blood circulation longer, tumor-specific targeting ability. Biotin-targeted dendritic:

单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
Figure 3: dendrimer biotin targeted for cell imaging
单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
FIG 4 macromolecular for in vivo tumor imaging

4, multivalent targeting dendritic probe can specifically target tumor, tumor tissue fluorescence in a stable and durable, and can achieve accurate definition of boundaries of the tumor, in fluorescence image of the surgical navigation exhibit excellent potential.

单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
Figure 5: Targeting of biotin long targeted dendrimer vivo imaging
单分子有机荧光纳米点在肿瘤成像与手术导航中的潜在应用
Figure 6: Detection and Fluorescence metastases surgical navigation

The full text link: https: //pubs.acs.org/doi/10.1021/acsnano.0c01034

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