Project 1: In vitro Studies: Correlate the physical and chemical characteristics

项目 1：体外研究：关联物理和化学特性

基本信息

批准号：
8274469
负责人：
David L Eaton
金额：
$ 25.55万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8274469
关键词：
Achievement Acids Acute Address Adverse effects Affect Air Albumins Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antibodies Antioxidants Apolipoprotein E Apoptosis Area Asbestos Attention Beryllium Biliverdine Binding Biocompatible Biological Biological Availability Biological Markers Biological Sciences Biotin Bone Marrow CCL2 gene CD3 Antigens CXCL2 gene Cadmium Cadmium chloride Carbon Nanotubes Cell Culture Techniques Cell Line Cell Survival Cells Characteristics Charge Chemicals Chromosome Mapping Coculture Techniques Collaborations Color Communities Complementary DNA Complex Cosmetics Cysteamine DNA Damage Data Dendritic Cells Detection Development Diesel Exhaust Drug Formulations Dyes Effectiveness Embryo Endothelial Cells Enzymes Epithelial Epithelial Cells Exposure to Fiber Figs - dietary Fluorescence Fluorescent Dyes Fluorescent Probes Free Radicals Fullerenes GCLC gene GCLM gene Gene Expression Generations Genes Genetic Transcription Glutamate Carboxypeptidase II Glutamate-Cysteine Ligase Glutamine Goals Heavy Metals Heme Hepatocyte Human Hydrocarbons Image Implant In Vitro Inbred Strains Mice Inflammation Inflammatory Inflammatory Response Inflammatory Response Pathway Injury Ink Interleukin-2 Interleukin-6 Intraperitoneal Injections Invertebrates Investigation Kidney Knockout Mice Lead Life Ligands Link Liquid substance Liver Lung Lysosomes Maleic Anhydride Measures Medical Messenger RNA Metabolism Metals Mind Mitochondria Modeling Modification Molecular Profiling Monoclonal Antibodies Mus NADP Nanotechnology Nature Necrosis Nose Nuclear Nuclear Localization Signal Nucleic Acids Occupational Optics Oxidation-Reduction Oxidative Stress Paint Paper Particle Size Particulate Pathway interactions Peptide antibodies Peritoneal Peritoneal Macrophages Phase Phosphate Buffer Photobleaching Photosensitization Polymers Predisposition Property Prostatic Neoplasms Proteins Publishing Quantum Dots Relative (related person)Reporting Research Research Personnel Respiratory System Respiratory tract structure Response Elements Risk Assessment Saline Sampling Scientist Selenium Semiconductors Signal Transduction Silicon Dioxide Site Small Interfering RNA Solid Solutions Source Spleen Sports Equipment Streptavidin Stress Structure Structure of respiratory epithelium Surface Surface Properties System T-Lymphocyte TNF gene Testing Thrombosis Time Tissues Toxic effect Transcription Repressor/Corepressor Tubular formation Vaccine Adjuvant Validation Vanadium Vascular Endothelial Cell Water Work absorption aerosolized antibody conjugate antimicrobial base bioimaging biomaterial compatibility cancer cell cell injury cell type chemokine commercial application cytokine cytotoxic design electronic structure enhanced green fluorescent protein experience fluorescence imaging fluorophore functional group heme oxygenase-1 human tissue imaging modality imaging probe in vivo interest lung injury lymph nodes lymphocyte proliferation macrophage metal oxide monocyte mouse model nanoGold nanocrystal nanomaterials nanoparticle nanoscale neutrophil new technology novel novel therapeutics optical imaging particle photoactivation photonics practical application promoter protein expression quantum receptor research study respiratory response sensor sertoli cell small molecule tissue/cell culture toxic metal trioctyl phosphine oxide tumor uptake water solubility zeta potential

项目摘要

Recent advances in nanotechnology have produced a multitude of nanoparticle types for use in many different products, including paints and inks, electroluminescent displays, solar panels, antimicrobials, cosmetics and sporting equipment. Semiconductor quantum dots (Qdots) are novel nanoparticles that have recently received a lot of attention because their unique photochemical and photophysical properties hold promise for a number of commercial applications including optoelectronics, counterfeiting inks, photovoltaics and biomedical imaging. Qdots have recently become broadly available to the scientific community through several commercial sources and many researchers are using Qdots as fluorescence imaging probes because their spectral properties are superior to traditional organic fluorophores [15, 16]. Qdots are several thousand times more stable against photobleaching than organic dye molecules and are thus well suited for continuous tracking studies over long time periods [17,18]. Qdots have large Stokes shifts and their broad absorption profiles allow simultaneous imaging of multiple colors within a biological sample and their emission wavelengths can be continuously tuned by varying particle size and/or chemical composition. Because of these unique optical properties, many of the current applications of Qdots have been focused on sensitive and quantitative bioimaging [15, 16,19], and on photosensitization and photoactivation therapies [20, 21]. In addition, we have recently demonstrated that Qdots can act as efficient intracellular delivery systems for novel therapeutics such as small inhibitory RNAs [22]. In general, the crystalline cores of Qdots are insoluble in water, and unless coated with a cap structure (e.g. ZnS) they also tend to be unstable, causing them to release their heavy metal core constituents making them less biocompatible and potentially toxic, thus limiting their usefulness for bioimaging and biomedical applications. In order to address the issues of water solubility, stability, biocompatibility, and toxicity, many groups have focused on the development of stabilizers and amphiphilic coatings to retain the photoluminescent properties of Qdots, while simultaneously providing a platform for further derivitization with antibodies, nucleic acids or other useful ligands [22-27]. We have recently synthesized CdSe/ZnS Qdots coated with tri-n-octylphosphine oxide (TOPO), and poly(maleic anhydride-alt-1-tetradecene (PMAT; a hydrocarbon polymer). These particles are exceptionally stable, retaining their fluorescence properties for at least 1 year when suspended in pH 7 phosphate buffered saline (PBS) and held at RT. Furthermore, the carboxyl functional groups present in this coating makes it convenient for ligand attachment. Similarly modified Qdots have shown promise for tumor targeting in vivo using antibodies directed against surface receptors on cancer cells [14, 28]; and for siRNA delivery [22]. As indicated above, concerns have been expressed regarding the biocompatibility and toxicity of Qdots and this has been primarily focused on their potential to degrade in vivo, thus releasing cadmium, selenium or other toxic metals [24, 29, 30]. In addition, many studies of nanoparticle toxicity have focused on their ability to incite oxidative stress and/or free radical-based cellular injury [31-36], and some Qdots have been shown to cause oxidative stress in vivo in an invertebrate model [37]. Many nanoparticles are also known to be proinflammatory, especially when taken up by tissue macrophages that can elaborate pro-inflammatory cytokines and chemokines [38-40]. Furthermore, the surface modifications made to these particles may themselves be problematic, and might lead to undesirable effects such as thrombosis [41], or off target accumulation by reticulo-endothelial cells (primarily macrophages and dendritic cells) in the liver, spleen and lymph nodes [30, 40]. Several recent studies have addressed the potential of unstable Qdots or nucleic acid -modified Qdots to elicit a pro-inflammatory response in vitro and in vivo. Commercially available unstable non-capped Qdots were shown to be highly inflammatory when instilled into the lungs of ApoE null mice, an animal model of increased susceptibility to particle-induced lung injury [42]. These authors attributed the strong inflammatory response of these CdTe Qdots to the release of Cd. In another recent report, Qdots conjugated with the cDNA for enhanced green fluorescent protein (eGFP) were similarly shown to induce an inflammatory response in cultured mouse peritoneal macrophages in vitro, and in vivo after intraperitoneal injection in mice [43]. However, this study attributed the inflammatory response to the presence of nucleic acid on the surface of the Qdots because similarly constructed Qdots without the nucleic acid added were not inflammatory. In this investigation we established that TOPO-PMAT coated CdSe/ZnS Qdots are moderately toxic to cultured mouse and human macrophage-like cells, and that short-term exposure is associated with changes in the expression of proteins and cellular factors that are biomarkers of oxidative stress. Importantly, these Qdots also increased the expression and secretion of several pro-inflammatory cytokines, which suggests that they are likely to elicit an acute inflammatory response in vivo. Many particles and fibers are known to be proinflammatory, including crystalline silica, asbestos and ambient air particulates (e.g. diesel exhaust particles) which can have both local effects on the respiratory systems as well as more systemic effects. Nanoparticles such as carbon nanotubes, fullerenes and metal oxides (e.g. TiOa, CeOa) have also been shown to induce oxidative stress in vitro, and to cause inflammation in the lungs of exposed animals [44, 45]. In recent reviews of Qdot toxicity [29, 30], the adverse effects of Qdots were attributed to many factors, including Qdot instability and the release of the heavy metal core constituents, electronic structure, free radical generation, and in some cases the material used to cap the Qdot core (e.g. ZnS, mercaptoacetic acid, etc.). However, it is also recognized that in addition to the composition of the semiconductor core and capping materials, the constituents that are used to coat Qdots, and surface charge (zeta potential) are important determinants of cellular uptake and stability. In order to further stabilize Qdots and minimize their degradation, we synthesized them with a highly stable TOPO-PMAT polymer coating, which allows them to retain their fluorescent properties (an indication of core integrity) for extended periods of time. While the TOPO-PMAT Qdots were not found to be highly cytotoxic (likely due to their relative stability), we did note changes suggestive of an adaptive response to oxidative stress, including changes in NADPH and GSH levels. Because Qdots have been shown to induce oxidative stress in some models, we also decided to evaluate the expression of glutamate cysteine ligase (GCL) and heme oxygenase-1 (HMOX-1), two proteins whose expression is often induced when cells experience oxidative stress. GCL is the rate limiting enzyme in GSH synthesis and is composed of catalytic and modifier subunits (GCLC and GCLM, respectively). These GCL subunits are often induced in response to oxidative stress, primarily through the activation of the Nrf2/Keap1 pathway [46-48], and can thus serve as useful biomarkers of oxidative challenge. Increased levels of HM0X1 seemed to be the most consistent indicator of QD-induced stress measured in this study (Fig 7). HM0X1 catabolizes heme to biliverdin, which has antioxidant properties [49]. Induction of HMOX1 has been shown to be highly dependent upon the degradation of the transcriptional repressor Bachi [50], which can bind to antioxidant response elements (AREs) present in the promoters of many Phase II and oxidative stress-responsive genes ([51, 52]. Because Bachi has been shown to be degraded when cells are exposed to Cd, it may be that slow degradation of these Qdots in lysosomes releases enough Cd to effect this change in Bachi [53]. However, HM0X1 is.also responsive to a number of signals that increase the expression of pro-inflammatory cytokines, including NFkB [54]. It has recently been argued that HM0X1 is anti-inflammatory and may actually suppress the release of inflammatory cytokines [55], and thus HM0X1 induction may represent a means by which the inflammatory response and the oxidative stress associated with it are limited in nature. Our results suggest that TOPO-PMAT modified Qdots might elicit a pro-inflammatory response in vivo. The secreted cytokines we detected after exposure of both RAW and THP-1 cells to Qdots (IL-lb, TNF-a, MCP-1, MIP1-a, and MIP2) are important because they are known to be important for inflammation, and neutrophil and monocyte/macrophage influx into the mouse lung after particle injury [56-58]. Their expression is governed at least in part by NFkB-dependent transcription [59-62]. Other groups have also begun to examine the potential for various kinds of Qdots to cause inflammation. Hoshino and co-workers [63] reported on a study in which CdSe/ZnS Qdots were modified with a polycysteine/glutamine coating, conjugated with streptavidin, which were then used to bind biotinylated-eGFP cDNAs. Finally, biotinylated-nuclear localization signaling peptides (NLSP) were also bound to these Qdots to facilitate cellular uptake, nuclear localization and eGFP expression [63]. These Qdots were readily taken up by HEK293T cells, showed no/minimal toxicity, and were effective at delivering gene constructs, as evidenced by the expression of eGFP. However, in a subsequent and recently published paper, this same group assessed the ability of these eGFP cDNA-modified Qdots and albumin-biotin-streptavidin modified Qdots to cause inflammation in vitro and in vivo [A3]. The albumin-streptavidin modified Qdots repressed lymphocyte proliferation in vitro, but did not affect the ability of T cells to secrete IL-2 or IFNy after stimulated with anti-CD3 monoclonal antibody. Similariy, albumin-streptavidin modified Qdots did not significantly increase the secretion of the pro-inflammatory cytokines IL-6, IL-ip or TNFa by cultured mouse peritoneal macrophages. These authors also found no effect of these Qdots on inflammatory, homeostatic, or dual-function chemokines mRNAs in bone marrow derived or peritoneal macrophages exposed in vitro. However, when eGFP cDNAmodified Qdots were injected into the peritoneal space, there was a robust inflammatory response. Importantly there was no inflammatory response when the mice were injected with Qdots modified only with the NLSP, indicating that this inflammatory response was likely caused by the cDNA complexes (possibly by interacting with TLR9 on macrophages). Indeed, exposure of peritoneal macrophages to eGFP cDNA modified Qdots in v/Yro elicited a pro-inflammatory cytokine response (TNFa and MIP1a), whereas NLSP-modified Qdots did not. In a report by Jacobson and co-workers, the mRNAs for the inflammatory cytokines IL-6, MIP2 and MCP1, the % neutrophils and protein levels in BAL, and DNA damage in BAL cells were all found to be increased in the lungs of mice that had been exposed to CdTe Qdots by intratracheal instillation [42]. It should be noted that these Qdots contained no cap structure, and were only modified with either mercaptopropionic acid (negatively charged) or cysteamine (positively charged). Because these Qdots were presumably unstable, the authors attributed the strong inflammatory response to the release of Cd by this particular formulation of Qdots. In summary, even though the stable TOPO-PMAT modified Qdots used in this study were of limited toxicity, they did induce the release of pro-inflammatory cytokines/chemokines from cultured macrophage cell lines, suggesting that they may cause an inflammatory response in vivo. Preliminary data obtained with mice exposed to TOPO-PMAT Qdots via nasal instillation indicates that this is indeed the case (see Project 2). Many nanoparticle formulations are being developed as adjuvants for vaccines [40]. It may be that the proinflammatory responses seen in this study could represent an advantage in that it could increase the effectiveness of anti-tumor responses. Nonetheless, as with many new technologies, the excitement and promise of Qdots for medical therapies is tempered by the data we and others have collected regarding their potential to cause adverse effects.

纳米技术的最新进展已生产出多种纳米颗粒类型，用于许多不同的产品，包括油漆和墨水，电动发光显示器，太阳能电池板，抗菌剂，化妆品，化妆品和运动设备。半导体量子点（QDOT）是新的纳米颗粒，最近受到了很多关注，因为它们的独特光化学和光学特性对数字有希望商业应用，包括光电，假冒墨水，光伏和生物医学成像。 QDOT最近通过多个商业来源广泛地为科学界广泛使用，许多研究人员将QDOTs用作荧光成像探针，因为它们的光谱特性优于传统的有机荧光团[15，16]。与有机染料分子相比，针对光漂白的QDOTS稳定性高几千倍，因此非常适合于长时间的连续跟踪研究时间段[17,18]。 QDOTS具有较大的Stokes偏移，它们的广泛吸收曲线可以同时对生物样品中的多种颜色进行成像，并且它们的发射波长可以通过不同的粒径和/或化学组成来连续调节。由于这些独特的光学特性，QDOT的许多当前应用都集中在敏感和定量的生物成像上[15，16,19]，以及ON 光敏和光活化疗法[20，21]。此外，我们最近证明了QDOT可以充当新型治疗剂（例如小抑制性RNA）的有效细胞内递送系统[22]。通常，QDOTS的结晶芯在水中不溶于水，除非覆盖有盖结构（例如Zns），否则它们也倾向于不稳定，从而释放其重金属核心成分，从而使其生物相容性较低，从而使其具有毒性和潜在有毒，从而限制了它们对生物成像和生物医学应用的有用性。为了解决水溶性，稳定性，生物相容性和毒性的问题，许多小组都集中在稳定剂和两亲性涂层的发展上，以保留光致发光 QDOTS的性质，同时提供了一个用抗体，核酸或其他有用的配体进一步衍生化的平台[22-27]。我们最近合成了与三辛基膦氧化物（TOPO）和聚（Malecic arthride-Alt-1-二烯烯（PMAT；碳氢化合物聚合物）涂层的CDSE/ZNS QDOT。这些颗粒非常稳定，至少在ph plasted（phossed phossed and phospere perte pert）中保持了荧光特性，并保持了phossecties的含量。此外，此涂层中存在的羧基官能团使其方便配体附着方便。使用针对癌细胞表面受体的抗体[14，28]；和siRNA输送[22]。如上所述，人们对QDOT的生物相容性和毒性表示关注，这主要集中在其体内降解的潜力上，从而释放了镉，硒或其他毒性金属[24，29，30]。此外，许多对纳米颗粒毒性的研究都集中在煽动氧化应激和/或基于自由基的细胞损伤的能力上[31-36]，并且一些QDOTS已被证明是在无脊椎动物模型中引起体内氧化应激[37]。已知许多纳米颗粒是促炎性的，尤其是在被可以详细说明促炎性细胞因子和趋化因子和趋化因子的组织巨噬细胞所吸收时[38-40]。此外，对这些粒子进行的表面修饰本身可能是有问题的，可能会导致不良影响，例如血栓形成[41]，或者通过靶标积累。肝脏，脾脏和淋巴结中的网状内皮细胞（主要是巨噬细胞和树突状细胞）[30，40]。最近的几项研究探讨了不稳定的QDOTS或核酸修饰的QDOTS在体外和体内引起促炎反应的潜力。当灌输到Apoe Null小鼠的肺中时，市售的不稳定的非封闭QDOT被证明是高度炎症的，APOE NULL小鼠是一种增加对颗粒引起的肺损伤敏感性的动物模型[42]。这些作者归因于强烈的炎症这些CDTE QDOTS对CD释放的响应。在最近的另一份报告中，与cDNA结合以增强绿色荧光蛋白（EGFP）的QDOT类似地显示出在体外诱导培养的小鼠腹膜巨噬细胞的炎症反应，在小鼠腹中注射后体内在体内诱导炎症反应[43]。然而，这项研究归因于QDOTS表面上存在核酸的炎症反应，因为没有添加核酸的类似构造的QDOT并非炎症。在这项调查中，我们确定了托托涂层的CDSE/ZnS QDOTS对培养的小鼠和人类巨噬细胞样细胞中等毒性，并且短期暴露与蛋白质表达的变化和细胞因子的表达变化有关，这些因素是氧化应激的生物标志物。重要的是，这些QDOT还增加了几种促炎细胞因子的表达和分泌，这表明它们是可能会在体内引起急性炎症反应。已知许多颗粒和纤维都是促炎的，包括晶体二氧化硅，石棉和环境空气颗粒（例如柴油排气颗粒），它们既可以对呼吸系统以及更多系统性效应产生局部影响。纳米颗粒（例如碳纳米管，富勒烯和金属氧化物（例如Tioa，ceoA））也已显示出诱导体外氧化应激，并在暴露动物的肺中引起炎症[44，45]。在最近对QDOT毒性的评论[29，30]中，QDOT的不利影响归因于许多因素，包括QDOT不稳定性和重金属核心成分，电子结构，自由基产生以及某些因素的释放用来限制QDOT核心的材料（例如Zns，胃乙酸等）。但是，还认识到，除了半导体核心和封盖材料的组成之外，用于涂层QDOTS的成分以及表面电荷（Zeta电位）是细胞摄取和稳定性的重要决定因素。为了进一步稳定QDOT并将其降解最小化，我们用高度稳定的Topo-PMAT聚合物涂层合成它们，这使它们可以保留其荧光长时间的属性（核心完整性的指示）。虽然未发现TOPO-PMAT QDOT是高度细胞毒性的（可能是由于它们的相对稳定性引起的），但我们确实注意到变化暗示了对氧化应激的适应性反应，包括NADPH和GSH水平的变化。由于QDOT已显示出在某些模型中诱导氧化应激当细胞经历氧化应激时，通常会诱导其表达。 GCL是GSH合成中酶的速率限制酶，由催化和修饰符亚基（分别为GCLC和GCLM）组成。这些GCL亚基通常是响应氧化应激而诱导的，主要是通过NRF2/KEAP1途径的激活[46-48]，因此可以用作氧化挑战的有用生物标志物。 HM0X1水平的升高似乎是本研究中测得的QD诱导应力的最一致的指标（图7）。 HM0X1将血红素分解为双甲脂蛋白，其具有抗氧化特性[49]。 HMOX1的诱导已被证明高度依赖于转录阻遏物Bachi [50]的降解，该降解可以与许多II期和启动子中存在的抗氧化反应元件（ARES）结合氧化应激响应性基因（[51，52]。由于已显示出BACHI在暴露于CD的细胞时已降解，因此可能会在溶酶体中释放出足够的CD中这些QDOTS的缓慢降解，以实现这种变化，以实现Bachi的变化[53]。但是，HM0X1的症状均增加了一定的cy症，以增加数量的表达，数量的数量n symers n n sarme n n sarme n n sarme n n symer n s syme n symer symb sym symb sym sym sembles n n symer n s syme n s syme n n sarme n n symer n n symb symb [54]。诱导可能代表一种炎症反应和与之相关的氧化应激的手段。我们的结果表明，TOPO-PMAT修饰的QDOT可能会在体内产生促炎反应。我们发现RAW和THP-1细胞在QDOTS（IL-LB，TNF-A，MCP-1，MIP1-A和MIP2）暴露后发现的分泌细胞因子很重要，因为它们对炎症非常重要，中性粒细胞和单细胞/巨噬细胞和单细胞/巨噬细胞受伤后的颗粒肺肺肺肿大[56-58]。它们的表达至少部分由NFKB依赖性转录[59-62]。其他组也开始研究各种QDOT引起炎症的潜力。 Hoshino及其同事[63]在一项研究中报道了CDSE/ZnS QDOTS与链霉亲蛋白结合的多膜半胱氨酸/谷氨酰胺涂层修饰，然后将其用于结合生物素化-EGFP cDNA。最后，生物素基化核定位信号传导肽（NLSP）也与这些QDOT结合，以促进细胞摄取，核定位和EGFP表达[63]。这些QDOT很容易被 HEK293T细胞没有/最小毒性，并且有效地传递基因构建体，如EGFP的表达所证明。然而，在随后且最近发表的论文中，同一组评估了这些EGFP cDNA修饰的QDOTS和白蛋白 - 生物蛋白 - 抗蛋白酶 - 链霉亲素修饰的QDOTS的能力，从而在体外和体内引起炎症[A3]。白蛋白 - 链霉亲和素修饰的QDOTS抑制淋巴细胞体外增殖，但不影响用抗CD3单克隆抗体刺激后T细胞分泌IL-2或IFNY的能力。类似的，蛋白 - 链霉亲和素修饰的QDOTS并未显着增加培养的小鼠腹膜巨噬细胞IL-6，IL-IP或TNFA的促炎细胞因子IL-6，IL-IP或TNFA的分泌。这些作者还发现这些QDOT对炎症，稳态或双功能趋化因子没有影响在体外暴露的骨髓中的mRNA或腹膜巨噬细胞。但是，当将EGFP CDNAMADIFIED QDOT注射到腹膜空间中时，会有强大的炎症反应。重要的是，当小鼠被仅用NLSP修饰时，没有炎症反应，表明这种炎症反应可能是由cDNA复合物引起的（可能是通过相互作用与巨噬细胞上的TLR9）。实际上，腹膜巨噬细胞暴露于EGFP cDNA中的V/yro修饰QDOTS引起了促炎性细胞因子反应（TNFA和MIP1A），而NLSP-Modified QDOTS则没有。在雅各布森和同事的报告中，炎性细胞因子IL-6，MIP2和MCP1的mRNA，BAL中的中性粒细胞和蛋白质水平的％和BAL细胞中的DNA损伤都在暴露于CDTE QDOTS的小鼠肺中增加。应该注意的是，这些QDOT不包含CAP结构，并且仅用任何一种胃丙酸修饰（负）充电）或cysteamine（带正电荷）。由于这些QDOT大概是不稳定的，因此作者将强烈的炎症反应归因于CD释放的强烈炎症反应。总而言之，尽管本研究中使用的稳定的TOPO-PMAT修饰的QDOT的毒性有限，但它们确实诱导了从培养的巨噬细胞系中释放促炎性细胞因子/趋化因子/趋化因子/趋化因子，这表明它们可能在体内引起炎症反应。通过鼻滴暴露于Topo-PMAT QDOTS获得的小鼠获得的初步数据表明确实是这种情况（请参阅项目2）。许多纳米颗粒制剂正在作为疫苗的佐剂开发[40]。这项研究中看到的促炎反应可能代表了一个优势，因为它可以提高抗肿瘤反应的有效性。尽管如此，与许多新技术一样，QDOTS对医疗疗法的兴奋和承诺受到我们和其他人对它们造成不利影响的潜力收集的数据的调节。