Ultralong tumor retention of theranostic nanoparticles with short peptide-enabled active tumor homing.
Ultralong tumor retention of theranostic nanoparticles with short peptide-enabled active tumor homing.
复制标题
具有短肽活性肿瘤归巢功能的治疗诊断纳米粒子的超长肿瘤保留
DOI：
10.1039/c9mh00014c
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发表时间：
2019
影响因子：
13.3
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Li L;Lu Y;Lin Z;Mao AS;Jiao J;Zhu Y;Jiang C;Yang Z;Peng M;Mao C
计算机断层扫描（CT）和磁共振成像（MRI）是临床中无创的癌症成像方法。因此，一种能够实现MRI/CT双模成像引导治疗的材料需求量很大。目前，可用的材料缺乏肿瘤的主动靶向性、肿瘤的深度穿透性和肿瘤的超长滞留性，可能会失去其成像要素。为了克服这些缺点，本文通过将MRI增强对比的螯合钆（Gd）复合物整合到负载阿霉素（DOX）的保护性硅壳中以及CT成像/光热生物相容性铋（Bi）纳米核中来开发纳米颗粒（NPs），该纳米核表面显示MCF-7乳腺肿瘤归主肽（AREYGTRFSLIGGYR，称为AR）；我们发现所得的NPs AR-Bi@SiO2-Gd/DOXNPs可以在AR肽的引导下，进入并深入肿瘤，并具有至少14天的超长保留时间（通过CT/MRI成像确定）和104.5小时的肿瘤保留半衰期（通过ICP-MS分析确定）。这些NPs可以进一步用于通过CT和MRI显着增加鲜明对比的肿瘤成像，这比商业标准造影剂好得多；此外，它们通过双氧联用光热疗法和dox诱导化疗的协同作用，显著抑制肿瘤生长。NPs被脾脏、肝脏和肾脏清除，然后随粪便和尿液排出体外。这些独特的NPs的精确肿瘤靶向和超长肿瘤保留将使精确的肿瘤检测用于早期诊断和信号持续的肿瘤跟踪用于监测治疗，只需单次注射这些NPs。一种短的乳腺肿瘤归巢肽可以引导治疗性纳米颗粒到达肿瘤并使其超长肿瘤滞留，从而实现高效的靶向乳腺癌CT/MRI双峰成像和光热化疗。
Computer tomography (CT) and magnetic resonance imaging (MRI) are noninvasive cancer imaging methods in clinics. Hence, a material that enables MRI/CT dual-modal imaging-guided therapy is in high demand. Currently, the available materials lack active tumor targeting, deep tumor penetration, and ultralong tumor retention and may lose their imaging elements. To overcome these drawbacks, herein, nanoparticles (NPs) were deveopled by integrating an MRI contrast-enhancing chelated gadolinium (Gd) complex within a doxorubicin (DOX)-loaded protective silica shell as well as a CT imaging/photothermal biocompatible bismuth (Bi) nano-core, which surface-displayed an MCF-7 breast tumor-homing peptide (AREYGTRFSLIGGYR, termed AR); we found that the resultant NPs AR-Bi@SiO2-Gd/DOXNPs could home to and penetrate deep into the tumors with the unexpected ultralong retention of at least 14 days (as determined by CT/MRI imaging) and the tumor retention half-life of 104.5 h (as determined by ICP-MS analysis) under the guidance of the AR peptide. These NPs can be further used to image tumors with significantly increased sharp contrasts via both CT and MRI, which are much better than the commercial standard contrast agents; moreover, they significantly inhibit tumor growth via the synergistic action of both Bi-enabled photothermal therapy and DOX-induced chemotherapy. The NPs are cleared by the spleen, liver and kidney and then excreted from the body along with faeces and urine. The precise tumor targeting and ultralong tumor retention of these unique NPs would enable both precise tumor detection for early diagnosis and signal-persistent tumor tracking for monitoring the treatment with only a single injection of these NPs. A short breast tumor-homing peptide can guide the theranostic nanoparticles to the tumors and enable their ultralong tumor retention, leading to highly efficient targeted breast cancer CT/MRI bimodal imaging and photothermal-chemotherapy.