Gadolinium(III) (Gd(III)) chelates are promising compounds for developing MRI‐guided neutron capture therapies (NCT). However, despite their success as MRI contrast agents (CAs), current Gd(III) chelates do not present appropriate accumulation in tumors for effective NCT. To overcome this limitation, we developed a series of biocompatible polymeric nanocarriers conjugating Gd(III)‐chelates, i. e. Gd‐DOTA, as NCT agents with high MRI sensitivity and tumor delivery. These polymers were based on poly(aspartic acid) (P(Asp)) and were modified with poly(ethylene glycol) (PEG) chains having different molecular weight (M_w) for controlling stability and pharmacokinetics. The T₁ relaxivity of the Gd‐DOTA conjugated polymers increased 2‐fold compared to that of clinically used Gd(III) CAs. In vivo, the PEG‐modified polymers promoted the accumulation in tumor tissues, enhancing the MRI contrast of tumors. After neutron irradiation, the nanocarriers effectively suppressed the tumor growth, particularly the PEG‐P(Asp‐Gd‐DOTA) with shorter PEG chain, which promoted higher intracellular delivery, supporting their potential as NCT agents.

中文翻译：

---

增强型MRI引导的d（III）中子捕获疗法，通过聚合物纳米载体促进肿瘤积累和细胞内递送。

d（Gd（III））螯合物是用于开发MRI引导的中子捕获疗法（NCT）的有前途的化合物。然而，尽管它们作为MRI造影剂（CA）取得了成功，但目前的Gd（III）螯合物在肿瘤中并未表现出有效NCT的适当蓄积作用。为了克服这一限制，我们开发了一系列与Gd（III）-螯合物结合的生物相容性聚合物纳米载体，即。e。Gd-DOTA，作为NCT剂，具有较高的MRI敏感性和肿瘤递送能力。这些聚合物基于聚天冬氨酸（P（Asp）），并用具有不同分子量（M _w）的聚乙二醇（PEG）链进行改性，以控制稳定性和药代动力学。T ₁与临床使用的Gd（III）CA相比，Gd-DOTA共轭聚合物的弛豫度提高了2倍。在体内，PEG修饰的聚合物促进了肿瘤组织中的积累，增强了肿瘤的MRI对比度。中子辐照后，纳米载体有效地抑制了肿瘤的生长，尤其是具有较短PEG链的PEG-P（Asp-Gd-DOTA），从而促进了更高的细胞内递送，支持了其作为NCT药物的潜力。