Surface-Modified Shortwave-Infrared-Emitting Nanophotonic Reporters for Gene-Therapy Applications.
Surface-Modified Shortwave-Infrared-Emitting Nanophotonic Reporters for Gene-Therapy Applications.
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DOI：
10.1021/acsbiomaterials.8b00378
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发表时间：
2018-07-09
影响因子：
5.8
通讯作者：
Tan MC
中科院分区：
文献类型：
--
作者：
Zhao Z;Kantamneni H;He S;Pelka S;Venkataraman AS;Kwon M;Libutti SK;Pierce M;Moghe PV;Ganapathy V;Tan MC
基因治疗正在成为下一代治疗方式，美国食品和药物管理局批准了针对癌症和罕见的眼部相关疾病的基因工程疗法，但实时监测靶向治疗反应的挑战仍然存在。在这项研究中，我们设计了一种由短波红外发射稀土掺杂纳米颗粒（RENP）组成的治疗诊断纳米颗粒，能够传递遗传物质并进行实时反应监测。我们发现，带有支链聚乙烯亚胺（PEI）的 RENP 的阳离子涂层对细胞毒性没有显着影响，可以通过使用反离子选择性修饰 PEI 涂层的表面特性来进一步降低细胞毒性，并扩大其在光热治疗中的潜在应用。我们在颗粒注射后长达 7 天的时间内在小鼠中展示了 RENPs@PEI 推注剂量的耐受性和清除率，此外 RENPs@PEI 能够以出色的信噪比在乳腺癌小鼠模型中明显辨别肺肿瘤病变。我们还展示了 RENP 上折叠的 PEI 链构象中胺官能团的可用性，这有助于在体外癌症模型中加载与目标基因杂交的遗传货物。在目标位点实时监测和提供基因治疗将使更多的基因和细胞治疗产品在临床试验中取得成功。
Gene therapy is emerging as the next generation of therapeutic modality with United States Food and Drug Administration approved gene-engineered therapy for cancer and a rare eye-related disorder, but the challenge of real-time monitoring of on-target therapy response remains. In this study, we have designed a theranostic nanoparticle composed of shortwave-infrared-emitting rare-earth-doped nanoparticles (RENPs) capable of delivering genetic cargo and of real-time response monitoring. We showed that the cationic coating of RENPs with branched polyethylenimine (PEI) does not have a significant impact on cellular toxicity, which can be further reduced by selectively modifying the surface characteristics of the PEI coating using counter-ions and expanding their potential applications in photothermal therapy. We showed the tolerability and clearance of a bolus dose of RENPs@PEI in mice up to 7 days after particle injection in addition to the RENPs@PEI ability to distinctively discern lung tumor lesions in a breast cancer mouse model with an excellent signal-to-noise ratio. We also showed the availability of amine functional groups in the collapsed PEI chain conformation on RENPs, which facilitates the loading of genetic cargo that hybridizes with target gene in an in vitro cancer model. The real-time monitoring and delivery of gene therapy at on-target sites will enable the success of an increased number of gene- and cell-therapy products in clinical trials.
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影响因子：
16.6
作者：
Naczynski, D. J.;Tan, M. C.;Zevon, M.;Wall, B.;Kohl, J.;Kulesa, A.;Chen, S.;Roth, C. M.;Riman, R. E.;Moghe, P. V.
通讯作者：
Moghe, P. V.
DOI：
10.1016/j.nano.2016.09.005
发表时间：
2017-01-01
影响因子：
5.4
作者：
Jagtap, Pramod;Sritharan, Venkataraman;Gupta, Shalini
通讯作者：
Gupta, Shalini
影响因子：
5.8
作者：
Sheng, Yang;Liao, Lun-De;Tan, Mei Chee
通讯作者：
Tan, Mei Chee
影响因子：
1.3
作者：
Stark, Marie;Cheng, R. Holland
通讯作者：
Cheng, R. Holland
用于功能生物分子成像和治疗诊断的稀土纳米探针。
DOI：
10.1039/c4tb00094c
发表时间：
2014-05-28
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Naczynski DJ;Tan MC;Riman RE;Moghe PV
通讯作者：
Moghe PV