Luo Dong, Johnson Andrew, Wang Xinning, Li Hao, Erokwu Bernadette O, Springer Sarah, Lou Jason, Ramamurthy Gopalakrishnan, Flask Chris A, Burda Clemens, Meade Thomas J, Basilion James P
Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, United States.
Department of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States.
Nano Lett. 2020 Oct 14;20(10):7159-7167. doi: 10.1021/acs.nanolett.0c02487. Epub 2020 Aug 31.
Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome and . The AuNPs binding affinity and relaxivity were dramatically improved and the combination of Au and Gd(III)provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.
辅助放疗常用于治疗癌症。为了将辐射对健康组织的相关损伤降至最低，它需要在肿瘤定位和辐射剂量输送方面具备高精度。这可以通过磁共振（MR）引导以及使用放射增敏剂将辐射剂量选择性地靶向放大至肿瘤来实现。在此，我们展示了用于MR引导放疗的靶向前列腺癌的金纳米颗粒（AuNP），以提高靶向精度和疗效。通过将钆（III）配合物和前列腺特异性膜抗原（PSMA）靶向配体缀合到AuNP表面，我们发现表达PSMA的癌细胞对AuNP的摄取增强，具有出色的MR对比度和放射治疗效果。AuNP的结合亲和力和弛豫率显著提高，并且金与钆（III）的组合在放疗后提供了更好的肿瘤抑制效果。MR对肿瘤的精确定位以及PSMA靶向AuNP对肿瘤的选择性靶向能够实现精确放疗、降低照射剂量并将健康组织损伤最小化。
