Intraoperative assessment and postsurgical treatment of prostate cancer tumors using tumor-targeted nanoprobes.
Intraoperative assessment and postsurgical treatment of prostate cancer tumors using tumor-targeted nanoprobes.
复制标题
使用肿瘤靶向纳米探针对前列腺癌肿瘤进行术中评估和术后治疗。
DOI：
10.7150/ntno.50095
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Perez JM
中科院分区：
文献类型：
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作者：
Teh J;Tripathi M;Reichel D;Sagong B;Montoya R;Zhang Y;Wagner S;Saouaf R;Chung LWK;Perez JM
在手术过程中成功可视化前列腺癌（PCa）肿瘤边缘仍然是一个重大挑战。手术期间通过近红外荧光（NIRF）成像对这些肿瘤进行可视化将大大增强手术切除，最大限度地减少肿瘤复发并改善结果。此外，化疗通常在手术后施用于患者，以治疗手术区域周围的任何遗漏的肿瘤组织，最大限度地减少转移并提高患者存活率。由于这些原因，可以开发治疗诊断荧光纳米颗粒以帮助PCa肿瘤边缘的可视化，同时还在手术后递送化疗药物。研究方法：Ferumoxytol（FMX）与荧光染料和PCa靶向剂七甲川羰花青（HMC）缀合，产生HMC-FMX纳米探针，其在体外用各种PCa细胞系和在体内用皮下和原位PCa小鼠模型进行测试。HMC-FMX给药后，通过NIRF成像对这些肿瘤进行可视化。此外，还评估了化疗药物的递送及其对肿瘤生长的影响。结果如下：HMC-FMX内化到PCa细胞中，用近红外荧光标记小鼠中的这些细胞和PCa肿瘤，促进肿瘤边缘可视化。HMC-FMX还能够向这些肿瘤输送药物，减少细胞迁移并减缓肿瘤生长。结论：HMC-FMX特异性靶向小鼠PCa肿瘤，允许通过NIRF成像可视化肿瘤边缘。此外，通过HMC-FMX递送抗癌药物在体外有效地减少了前列腺肿瘤生长并减少了细胞迁移。因此，HMC-FMX可以潜在地转化为临床作为nanotheranostics剂，用于PCa肿瘤边缘的术中可视化，以及用负载抗癌药物的HMC-FMX进行肿瘤的术后治疗。
Successful visualization of prostate cancer (PCa) tumor margins during surgery remains a major challenge. The visualization of these tumors during surgery via near infrared fluorescence (NIRF) imaging would greatly enhance surgical resection, minimizing tumor recurrence and improving outcome. Furthermore, chemotherapy is typically administered to patients after surgery to treat any missed tumor tissue around the surgical area, minimizing metastasis and increasing patient survival. For these reasons, a theranostics fluorescent nanoparticle could be developed to assist in the visualization of PCa tumor margins, while also delivering chemotherapeutic drug after surgery. Methods: Ferumoxytol (FMX) conjugated to the fluorescent dye and PCa targeting agent, heptamethine carbocyanine (HMC), yielded the HMC-FMX nanoprobe that was tested in vitro with various PCa cell lines and in vivo with both subcutaneous and orthotopic PCa mouse models. Visualization of these tumors via NIRF imaging after administration of HMC-FMX was performed. In addition, delivery of chemotherapeutic drug and their effect on tumor growth was also assessed. Results: HMC-FMX internalized into PCa cells, labeling these cells and PCa tumors in mice with near infrared fluorescence, facilitating tumor margin visualization. HMC-FMX was also able to deliver drugs to these tumors, reducing cell migration and slowing down tumor growth. Conclusion: HMC-FMX specifically targeted PCa tumors in mice allowing for the visualization of tumor margins by NIRF imaging. Furthermore, delivery of anticancer drugs by HMC-FMX effectively reduced prostate tumor growth and reduced cell migration in vitro. Thus, HMC-FMX can potentially translate into the clinic as a nanotheranostics agent for the intraoperative visualization of PCa tumor margins, and post-operative treatment of tumors with HMC-FMX loaded with anticancer drugs.