GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer.
GRP78-targeted and doxorubicin-loaded nanodroplets combined with ultrasound: a potential novel theranostics for castration-resistant prostate cancer.
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GRP78 靶向和阿霉素负载纳米液滴与超声相结合：一种治疗去势抵抗性前列腺癌的潜在新型治疗诊断学。
DOI：
10.1080/10717544.2021.2023698
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发表时间：
2022-12
期刊：
影响因子：
6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhao Y;Shi D;Shang M;Sun X;Guo L;Meng D;Liu X;Zhou X;Li J
构建结合诊断和治疗的多功能肿瘤治疗纳米平台仍然具有挑战性。纳米液滴（ND）可同时增强超声成像和治疗效果，是非侵入性药物输送的潜在策略。为了实现精准医疗的目标，本研究构建了用于去势抵抗性前列腺癌（CRPC）靶向和治疗的新型SP94肽修饰和阿霉素负载超声ND（SP94-DOX-ND）。评估了 SP94-DOX-ND 的特性、对比增强超声成像 (CEUI)、对葡萄糖调节蛋白 78 (GRP78) 过表达 CRPC 的靶向能力以及抗癌作用。采用一定比例的SP94-PEG-壳聚糖、全氟戊烷（PFP）、吐温20和卵磷脂，采用纳米乳化法成功制备了所需的SP94-ND。尺寸约为 300 nm 的 SP94-ND 显示出良好的生物相容性和 CEUI 能力。与空白ND相比，由于SP94肽与GRP78过表达的22RV1细胞之间的缀合，SP94-ND表现出更高的肿瘤特异性靶向能力。最重要的是，体外和体内研究表明，SP94-DOX-NDs 与超声结合可以特异性地将 DOX 递送到 22RV1 细胞中，从而表现出比 DOX-NDs 和 DOX 更强的抗癌作用。因此，SP94-DOX-ND 可以为肿瘤的实时成像和触发、准确的药物递送到肿瘤提供有效的方法。
The construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precise medicine, novel SP94 peptide-modified and doxorubicin-loaded ultrasonic NDs (SP94-DOX-NDs) for castration-resistant prostate cancer (CRPC) targeting and treatment were constructed in this study. The characteristics, contrast-enhanced ultrasound imaging (CEUI), targeting ability to glucose-regulated protein 78 (GRP78)-overexpressing CRPC and anticancer effect of the SP94-DOX-NDs were assessed. The desired SP94-NDs were successfully prepared using the nanoemulsification method using a certain proportion of SP94-PEG-chitosan, perfluoropentane (PFP), Tween 20, and lecithin. SP94-NDs with a size of ∼300 nm showed great biocompatibility and CEUI ability. Compared with blank NDs, SP94-NDs exhibited higher tumor-specific targeting ability due to conjugation between the SP94 peptide and GRP78-overexpressing 22RV1 cells. Most importantly, in vitro and in vivo investigations showed that SP94-DOX-NDs combined with ultrasound could specifically deliver DOX into 22RV1 cells and thereby demonstrated a stronger anticancer effect than DOX-NDs and DOX. Thus, SP94-DOX-NDs may provide an efficient approach for the real-time imaging of tumors and triggered, accurate drug delivery to tumors.
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