Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.
Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.
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通过配位化学放射性标记二氧化硅基纳米粒子：基本原理、策略和应用
DOI：
10.1021/acs.accounts.7b00635
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发表时间：
2018-03-20
影响因子：
18.3
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Ni D;Jiang D;Ehlerding EB;Huang P;Cai W
作为生物相容性和耐受性最好的无机纳米材料之一，硅基纳米颗粒（SiNPs）在过去几十年中受到了广泛的关注。最近，放射性标记的SiNP的正电子发射断层扫描（PET）成像提供了体内器官/组织分布、药代动力学和肿瘤靶向效率的高灵敏度、非侵入性和定量读出，这可以大大加快这些有前途的NP的临床转化。受使用124 I标记的超小SiNP（称为康奈尔点或C点）对患有转移性黑素瘤的患者进行成功PET成像以及它们被美国食品和药物管理局批准为研究性新药（IND）的鼓舞，不同的放射性同位素（64 Cu、89 Zr、18 F、68 Ga、124 I等）已经报道了放射性标记各种基于SiNP的纳米结构，包括致密二氧化硅（dSiO 2）、介孔二氧化硅（MSN）、可生物降解的介孔二氧化硅（bMSN）和中空介孔二氧化硅纳米颗粒（HMSN）。随着配位化学的深入了解，二氧化硅表面或中孔通道内丰富的硅烷醇基团（-Si-O-）不仅可以直接用于无螯合剂的放射性标记，而且可以很容易地用正确的螯合剂进行修饰，用于基于螯合剂的标记。然而，由于所涉及的关键参数的复杂性，如放射性同位素和螯合剂的选择，纳米结构和放射性标记策略，整合这些标记策略以高效率构建稳定的放射性标记的SiNP已被证明是困难的。在本报告中，我们概述了放射性标记的SiNPs用于癌症治疗诊断的最新进展，希望加快其生物医学应用和潜在的临床转化。我们首先介绍通过配位化学放射性标记SiNP的基本原理和机制，包括选择适当放射性同位素的一般规则、工程二氧化硅纳米平台（例如，dSiO 2，MSN，HMSN），以及增强标记效率和稳定性的螯合策略，我们的团队在过去十年中一直专注于此。通常，医学应用通过考虑SiNP的固有功能性来指导用于放射性标记的特定SiNP的选择。然后可以根据特定SiNP对基于螯合剂或不含螯合剂的放射性标记的顺从性来确定放射性同位素，以获得体内高标记稳定性，这是PET真实反映SiNP行为的先决条件，因为PET成像检测同位素而不是纳米颗粒。接下来，我们重点介绍放射性标记SiNP最近的几种代表性生物医学应用，包括检测特定病变的分子成像、PET引导的药物递送、基于SiNP的治疗诊断癌症药物和临床研究。最后，简要讨论了放射性标记SiNPs在临床癌症研究中面临的挑战和前景。我们希望这个帐户将澄清放射性标记的SiNPs的特定医疗应用的最新进展，并产生广泛的兴趣，整合纳米技术和PET成像。随着几项正在进行的临床试验，放射性标记的SiNP为临床环境中的未来患者分层和癌症管理提供了巨大的潜力。
As one of the most biocompatible and well-tolerated inorganic nanomaterials, silica-based nanoparticles (SiNPs) have received extensive attention over the last several decades. Recently, positron emission tomography (PET) imaging of radiolabeled SiNPs has provided a highly sensitive, noninvasive, and quantitative readout of the organ/tissue distribution, pharmacokinetics, and tumor targeting efficiency in vivo, which can greatly expedite the clinical translation of these promising NPs. Encouraged by the successful PET imaging of patients with metastatic melanoma using 124I-labeled ultrasmall SiNPs (known as Cornell dots or C dots) and their approval as an Investigational New Drug (IND) by the United States Food and Drug Administration, different radioisotopes (64Cu, 89Zr, 18F, 68Ga, 124I, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense silica (dSiO2), mesoporous silica (MSN), biodegradable mesoporous silica (bMSN), and hollow mesoporous silica nano-particles (HMSN). With in-depth knowledge of coordination chemistry, abundant silanol groups (–Si–O–) on the silica surface or inside mesoporous channels not only can be directly used for chelator-free radiolabeling but also can be readily modified with the right chelators for chelator-based labeling. However, integrating these labeling strategies for constructing stably radiolabeled SiNPs with high efficiency has proven difficult because of the complexity of the involved key parameters, such as the choice of radioisotopes and chelators, nanostructures, and radiolabeling strategy. In this Account, we present an overview of recent progress in the development of radiolabeled SiNPs for cancer theranostics in the hope of speeding up their biomedical applications and potential translation into the clinic. We first introduce the basic principles and mechanisms for radiolabeling SiNPs via coordination chemistry, including general rules of selecting proper radioisotopes, engineering silica nanoplatforms (e.g., dSiO2, MSN, HMSN) accordingly, and chelation strategies for enhanced labeling efficiency and stability, on which our group has focused over the past decade. Generally, the medical applications guide the choice of specific SiNPs for radiolabeling by considering the inherent functionality of SiNPs. The radioisotopes can then be determined according to the amenability of the particular SiNPs for chelator-based or chelator-free radiolabeling to obtain high labeling stability in vivo, which is a prerequisite for PET to truly reflect the behavior of SiNPs since PET imaging detects the isotopes rather than nanoparticles. Next, we highlight several recent representative biomedical applications of radiolabeled SiNPs including molecular imaging to detect specific lesions, PET-guided drug delivery, SiNP-based theranostic cancer agents, and clinical studies. Finally, the challenges and prospects of radiolabeled SiNPs are briefly discussed toward clinical cancer research. We hope that this Account will clarify the recent progress on the radiolabeling of SiNPs for specific medical applications and generate broad interest in integrating nanotechnology and PET imaging. With several ongoing clinical trials, radiolabeled SiNPs offer great potential for future patient stratification and cancer management in clinical settings.
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DOI：
10.1021/acs.chemmater.7b02567
发表时间：
2017-10-10
期刊：
Chemistry of materials : a publication of the American Chemical Society
影响因子：
--
作者：
Chen F;Ma K;Zhang L;Madajewski B;Zanzonico P;Sequeira S;Gonen M;Wiesner U;Bradbury MS
通讯作者：
Bradbury MS
影响因子：
4.9
作者：
Chen F;Nayak TR;Goel S;Valdovinos HF;Hong H;Theuer CP;Barnhart TE;Cai W
通讯作者：
Cai W
工程本质上是锆-89放射性标记的自毁介孔二氧化硅纳米结构，用于体内生物分布和肿瘤靶向研究。
影响因子：
15.1
作者：
Goel, Shreya;Chen, Feng;Luan, Shijie;Valdovinos, Hector F.;Shi, Sixiang;Graves, Stephen A.;Ai, Fanrong;Barnhart, Todd E.;Theuer, Charles P.;Cai, Weibo
通讯作者：
Cai, Weibo
影响因子：
16.1
作者：
Goel S;England CG;Chen F;Cai W
通讯作者：
Cai W
影响因子：
16.6
作者：
Chen, Feng;Ellison, Paul A.;Lewis, Christina M.;Hong, Hao;Zhang, Yin;Shi, Sixiang;Hernandez, Reinier;Meyerand, M. Elizabeth;Barnhart, Todd E.;Cai, Weibo
通讯作者：
Cai, Weibo