Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.
Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.
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作者：
Yang E;Qian W;Cao Z;Wang L;Bozeman EN;Ward C;Yang B;Selvaraj P;Lipowska M;Wang YA;Mao H;Yang L
了解免疫反应对纳米颗粒靶向递送的影响对于新的癌症成像和治疗纳米颗粒的临床转化非常重要。在这项研究中，我们发现，重复施用与小鼠或人源性靶向配体缀合的磁性氧化铁纳米颗粒（IONP）可在正常和荷瘤小鼠中诱导高水平的配体特异性抗体反应，而注射未缀合的小鼠配体的免疫原性较弱，并在小鼠中诱导非常低水平的抗体反应。由于巨噬细胞和树突状细胞对 PEG 涂层纳米颗粒的不同摄取，接受静脉注射靶向聚乙二醇 (PEG) 涂层的 IONP 的小鼠进一步增加了配体特异性抗体的产生。然而，在全身递送携带化疗药物阿霉素的治疗诊断纳米颗粒后，配体特异性抗体的产生明显受到抑制。靶向成像和组织学分析表明，配体特异性抗体的缺乏导致靶向纳米粒子的肿瘤内递送增加。这项研究的结果支持了进一步开发用于治疗人类癌症的靶向治疗纳米颗粒的潜力。
Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.
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影响因子：
4.9
作者：
Han H;Davis ME
通讯作者：
Davis ME
用于光学成像和治疗的新型肿瘤靶向药物载体
影响因子：
12.4
作者：
Li R;Zheng K;Hu P;Chen Z;Zhou S;Chen J;Yuan C;Chen S;Zheng W;Ma E;Zhang F;Xue J;Chen X;Huang M
通讯作者：
Huang M
DOI：
10.1073/pnas.0806335105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Lechmann, Matthias;Shuman, Naomi;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
17.1
作者：
Bartneck, Matthias;Keul, Heidrun A.;Groll, Juergen
通讯作者：
Groll, Juergen
影响因子：
82.9
作者：
Lee, Jae-Hyun;Huh, Yong-Min;Cheon, Jinwoo
通讯作者：
Cheon, Jinwoo