Glycodendrimers (Glyco-DDMs) represent a rapidly growing class of nanoparticles with promising properties for biomedical applications but concerns regarding the impact on human health and environment are still justified. Here we report, for the first time, the comparative study of in vivo developmental toxicity of carbosilane Glyco-DDMs and their cytotoxicity in vitro. Carbosilane Glyco-DDMs (generation 1–3) containing 4, 8, and 16 β-d-glucopyranosyl units at the periphery (DDM₁Glu, DDM₂Glu, and DDM₃Glu) were synthesized and characterized by ¹H, ¹³C and ²⁹Si NMR, mass spectrometry, dynamic light scattering, atomic force microscopy (AFM), and computer modeling. In vitro cytotoxicity assay (MTT) of DDM_1–3Glu was performed on three different rodent cell lines (Cricetulus griseus) – B14 (ATCC, CCL-14.1), BRL 3A (ATCC, CRL-1442), and NRK 52E (ATCC, CRL-1571). Overall, very low cytotoxicity was observed with calculated IC₅₀ in mM range with slight difference between each cell line and DDM generation investigated. Modified fish embryo test (FET) was further used for DDM₃Glu developmental toxicity testing on zebrafish (Danio rerio) embryos. While seemingly harmless to intact embryos, adverse effects of DDMs on the embryonic development become evident after chorion removal (LD₅₀=2.78 µM at 96 hpe). We summarized that the modified FET test showed a two to three orders of magnitude difference between the in vitro cytotoxicity and in vivo developmental toxicity of DDM₃Glu. While, in general, the Glyco-DDMs show great promises as efficient vectors in targeted drug delivery or as therapeutic molecules itself, we suggest that their developmental toxicity should be thoroughly investigated to exclude safety risks associated with their potential biomedical use.

中文翻译：

---

评价碳硅烷葡萄糖糖类树状聚合物在斑马鱼胚胎和啮齿动物模型细胞中的毒理和致畸作用

糖基增白剂（Glyco-DDMs）代表了一类快速增长的纳米颗粒，其在生物医学应用中的应用前景看好，但仍然存在着对人类健康和环境影响的担忧。在这里，我们首次报道了碳硅烷糖基DDM的体内发育毒性及其体外细胞毒性的比较研究。合成了在外围包含4、8和16个β - d-吡喃葡萄糖基的碳硅烷糖基DDM（1-3代）（DDM ₁ Glu，DDM ₂ Glu和DDM ₃ Glu）并通过¹ H，¹³ C表征和²⁹Si NMR，质谱，动态光散射，原子力显微镜（AFM）和计算机建模。DDM _1–3 Glu的体外细胞毒性测定（MTT）在三种不同的啮齿动物细胞系（Cricetulus griseus）– B14（ATCC，CCL-14.1），BRL 3A（ATCC，CRL-1442）和NRK 52E（ATCC）上进行，CRL-1571）。总体而言，在mM范围内计算出的IC ₅₀观察到非常低的细胞毒性，并且每个细胞系和DDM代之间存在细微的差异。进一步将改良的鱼胚测试（FET）用于斑马鱼（Danio rerio）的DDM ₃ Glu发育毒性测试）胚胎。虽然对完整的胚胎无害，但去除绒毛膜后DDM对胚胎发育的不利影响变得明显（在96 hpe时LD ₅₀ = 2.78 µM）。我们总结说，改良的FET测试显示DDM ₃ Glu的体外细胞毒性和体内发育毒性之间存在2至3个数量级的差异。通常，Glyco-DDM有望作为靶向药物输送的有效载体或作为治疗分子本身，具有广阔的前景，但我们建议应彻底研究其发育毒性，以排除与其潜在生物医学用途相关的安全风险。