Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, 400030, People's Republic of China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People's Republic of China.
Int J Nanomedicine. 2023 Apr 13;18:2003-2015. doi: 10.2147/IJN.S403887. eCollection 2023.
Prostate cancer (PCa) ranks second in the incidence of all malignancies in male worldwide. The presence of multi-organ metastases and tumor heterogeneity often leads to unsatisfactory outcomes of conventional radiotherapy treatments. This study aimed to develop a novel folate-targeted nanohydroxyapatite (nHA) coupling to deliver adriamycin (Doxorubicin, DOX), P, and Tc simultaneously for the diagnosis and treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer.
The spherical nHA was prepared by the biomimetic method and characterized. Folic acid (FA) was coupled to nHA with polyethylene glycol (PEG), and the grafting ratio of PEG-nHA and FA-PEG-nHA was determined by the thermogravimetric analysis (TGA) method. In addition, P, Tc, and DOX were loaded on nHA by physisorption. And the labeling rate and stability of radionuclides were measured by a γ-counter. The loading and release of DOX at different pH were determined by the dialysis method. Targeting of FA-PEG-nHA loaded with Tc was verified by in vivo SPECT imaging. In vitro anti-tumor effect of P/DOX-FA-PEG-nHA was assessed with apoptosis assay. The safety of the nano-drugs was verified by histopathological analysis.
The SEM images showed that the synthesized nHA was spherical with uniform particle size (average diameter of about 100nm). The grafting ratio is about 10% for PEG and about 20% for FA. The drug loading and the delayed release of DOX at different pH confirmed its long-term therapeutic ability. The labeling of P and Tc was stable and the labeling rate was great. SPECT showed that FA-PEG-nHA showed well in vivo tumor targeting and less damage to normal tissues.
FA-targeted nHA loaded with P, Tc, and DOX may be a new diagnostic and therapeutic strategy for targeting PSMA-positive prostate cancer tumors, which may achieve better therapeutic results while circumventing the severe toxic side effects of conventional chemotherapeutic agents.
前列腺癌（PCa）在全球男性恶性肿瘤发病率中排名第二。多器官转移和肿瘤异质性的存在常常导致传统放疗治疗效果不理想。本研究旨在开发一种新型叶酸靶向纳米羟基磷灰石（nHA），同时递送阿霉素（Doxorubicin，DOX）、P 和 Tc，用于诊断和治疗前列腺特异性膜抗原（PSMA）阳性前列腺癌。
采用仿生法制备球形 nHA，并对其进行了表征。通过聚乙二醇（PEG）将叶酸（FA）偶联到 nHA 上，通过热重分析（TGA）法测定 PEG-nHA 和 FA-PEG-nHA 的接枝率。此外，通过物理吸附将 P、Tc 和 DOX 负载到 nHA 上。通过 γ 计数器测量放射性核素的标记率和稳定性。通过透析法测定不同 pH 值下 DOX 的载药率和释放率。通过体内 SPECT 成像验证 FA-PEG-nHA 负载 Tc 的靶向性。通过凋亡试验评估 P/DOX-FA-PEG-nHA 的体外抗肿瘤作用。通过组织病理学分析验证纳米药物的安全性。
SEM 图像显示，合成的 nHA 呈球形，粒径均匀（平均直径约 100nm）。PEG 的接枝率约为 10%，FA 的接枝率约为 20%。不同 pH 值下 DOX 的载药率和延迟释放证实了其长效治疗能力。P 和 Tc 的标记稳定，标记率高。SPECT 显示 FA-PEG-nHA 具有良好的体内肿瘤靶向性，对正常组织损伤较小。
载有 P、Tc 和 DOX 的 FA 靶向 nHA 可能是一种针对 PSMA 阳性前列腺癌肿瘤的新型诊断和治疗策略，它可能在避免传统化疗药物严重毒性副作用的同时，实现更好的治疗效果。
