Theranostic Nanomedicine

Theranostic 纳米医学
  • 文章类型: Journal Article
    心脏毒性,癌症患者经常被忽视的第二大死亡原因,与某些抗癌药物有关。这些药物可以通过多种途径引起心脏损伤,它们对心脏的不利影响尚未完全了解。心脏毒性是癌症治疗中的一个主要问题。特别是化疗药物,因为它会导致心脏功能障碍,如低血压,心力衰竭,甚至死亡。阿霉素,5-氟尿嘧啶,和曲妥珠单抗,所有这些都是非常有效的抗癌药物,已知会引起心脏毒性。在降低心脏毒性和减轻化疗药物的有害影响方面,纳米药物具有运输治疗分子的潜力。Nanotheranosics为识别和治疗由多种物质引起的心脏毒性提供了新的选择,包括抗癌药物。此外,theranostics平台,如胶束系统,碳基纳米医学,固体脂质纳米粒,聚合物纳米颗粒,和脂质体可以运输化疗药物,同时最大限度地减少其心脏毒性。本文总结了对导致对传统化学疗法和靶向药物递送系统的心脏毒性的分子和细胞过程的理解水平。这篇综述深入研究了纳米医学和纳米治疗学,重点是减少抗癌药物引起的心脏毒性。Nanotheranosics通过将诊断和治疗能力结合到纳米医学中,为心脏损伤的早期诊断和定制治疗提供了潜在的解决方案。
    Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.
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  • 文章类型: Journal Article
    开发了一种用于细胞内miRNA成像和自给自足饥饿疗法(ST)和化学动力学疗法(CDT)的联合治疗的癌症靶向谷胱甘肽(GSH)门控治疗探针(CGT探针)。CGT探针是使用MnO2纳米片(MS)作为载体材料构建的,以吸附精心设计的功能DNA。它可以通过AS1411适体和核仁素之间的特异性识别被癌细胞内化。CGT探针进入癌细胞后,过度表达的GSH,作为栅极控制,可以通过类Fenton反应将MS降解为可用于CDT的Mn2。同时,Mn2+介导的CDT可以进一步与CGT探针的酶样活性(过氧化氢酶样活性和葡萄糖氧化酶样活性)级联,实现自给自足的ST/CDT协同治疗。同时,锚定的DNA被释放,通过miR-21的双取代催化发夹组装(DCHA)和FRET(荧光共振能量转移)成像实现原位信号放大。体外和体内实验表明,使用CGT探针可以实现准确和灵敏的miRNA检测。总的来说,巧妙的CGT探针为早期临床诊断和癌症治疗的发展开辟了新途径。
    A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.
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  • 文章类型: Journal Article
    原理:通过可缺氧激活的荧光探针对微环境进行分子成像已成为肿瘤诊断和图像引导治疗的有吸引力的方法。由于肿瘤微环境中的缺氧异质性,其翻译应用仍然存在困难,这使得将缺氧成像为肿瘤分布的可靠代表具有挑战性。方法:我们报告了一个模块化的治疗平台,通过光调制信号补偿来荧光可视化缺氧,以克服肿瘤异质性,从而作为图像引导的手术切除和光动力治疗的诊断工具。具体来说,该平台采用超分子主客体自组装集成荧光指示剂和光动力调节剂双模块,它作为级联的“与”逻辑门协作运行。首先,通过肿瘤受体和级联微环境信号作为“AND”门的同时输入,可以获得低氧区域的肿瘤富集和特定荧光开启。第二,由发光的荧光模块和光介导的光动力模块的内源性氧消耗作为双输入的图像引导“与”门协同启用原位光调制信号补偿,表明在整个肿瘤中增强的缺氧相关荧光信号的同质性。结果:在体外和体内分析,生物相容性平台展示了几种优势,包括双重肿瘤靶向的能力,以逐步促进特定的荧光开启,选择性信号补偿,成像时间窗口扩展有利于精确的规范化图像引导治疗,和肿瘤谷胱甘肽消耗的功能,以提高光动力功效。结论:缺氧激活,图像引导治疗平台在克服肿瘤缺氧异质性方面表现出极好的潜力.
    Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded \"AND\" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the \"AND\" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of \"AND\" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.
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  • 文章类型: Journal Article
    血管生成是形成新血管的生理过程,在癌症等看似无关的疾病中具有病理重要性,糖尿病,和各种炎症性疾病。针对血管生成的治疗对这些类型的疾病有希望,但目前的抗血管生成药物在递送和副作用方面具有严重的局限性。这需要探索替代方法,如基于生物分子的药物。蛋白质,脂质,寡核苷酸最近在生物医学中变得流行,特别是作为治疗药物的生物相容性成分。其优异的生物利用度和潜在的生物活性和免疫原性特性使其成为药物发现或药物递送系统的主要候选者。基于脂质的脂质体已成为靶向纳米颗粒(NP)递送的标准载体,而蛋白质和核苷酸NP显示出作为智能NP的环境敏感性递送的希望。它们的治疗应用最初受到循环时间短和制造困难的阻碍,但纳米加工和NP工程的最新发展已经找到了规避这些缺点的方法。大大提高了生物分子NP的实用性。在这次审查中,我们将简要讨论基于生物分子的NP如何改善基于抗血管生成的治疗.
    Angiogenesis is a physiological process of forming new blood vessels that has pathological importance in seemingly unrelated illnesses like cancer, diabetes, and various inflammatory diseases. Treatment targeting angiogenesis has shown promise for these types of diseases, but current anti-angiogenic agents have critical limitations in delivery and side-effects. This necessitates exploration of alternative approaches like biomolecule-based drugs. Proteins, lipids, and oligonucleotides have recently become popular in biomedicine, specifically as biocompatible components of therapeutic drugs. Their excellent bioavailability and potential bioactive and immunogenic properties make them prime candidates for drug discovery or drug delivery systems. Lipid-based liposomes have become standard vehicles for targeted nanoparticle (NP) delivery, while protein and nucleotide NPs show promise for environment-sensitive delivery as smart NPs. Their therapeutic applications have initially been hampered by short circulation times and difficulty of fabrication but recent developments in nanofabrication and NP engineering have found ways to circumvent these disadvantages, vastly improving the practicality of biomolecular NPs. In this review, we are going to briefly discuss how biomolecule-based NPs have improved anti-angiogenesis-based therapy.
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  • 文章类型: Journal Article
    动脉粥样硬化仍然是全球发病率和死亡率的主要原因。精确评估动脉粥样硬化斑块的范围对于预测其引起健康问题的可能性和跟踪治疗结果至关重要。与使用的常规方法相比,纳米颗粒为易感动脉粥样硬化斑块的检测和表征提供了明确的益处和极好的发展机会。在这次审查中,我们分析了纳米粒子作为动脉粥样硬化治疗的最新进展,重点是在药物输送中的应用。此外,讨论了为了提高NP研究的临床实用性和未来发展必须解决的主要问题。预计医疗NP将发展成为复杂和先进的下一代纳米机器人,可以在血液中执行各种功能。
    Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream.
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  • 文章类型: Journal Article
    这项研究通过使用沸石咪唑酯骨架8(ZIF-8)作为支架封装吲哚菁绿(ICG)和紫杉醇(Tax)来利用纳米技术。本研究旨在探讨ZIF-8@ICG@Tax纳米粒子(NPs)在非小细胞肺癌(NSCLC)治疗中的化学光热治疗潜力。通过基于静电相互作用的自组装进行“一体化”治疗ZIF-8@ICG@TaxNPs。首先,光热效应,稳定性,pH响应性,药物释放,通过体外测试评估ZIF-8@ICG@Tax的血液相容性。此外,通过体内试验评估ZIF-8@ICG@Tax的肝和肾毒性.此外,在体外和体内研究了这些纳米颗粒的抗癌作用。已成功合成了均匀稳定的化学光热ZIF-8@ICG@TaxNPs,并具有出色的药物释放能力。此外,ZIF-8@ICG@TaxNPs显示出显着的反应性,这取决于肿瘤微环境中的pH值和NIR照射,允许靶向药物递送和控制药物释放。NIR照射可以增强肿瘤细胞对ZIF-8@ICG@Tax摄取的反应,从而促进体内外抗肿瘤生长。ZIF-8@ICG@Tax和NIR辐照与它们各自的组分相比已显示出显著的协同抗肿瘤生长特性。这种新型的治疗-光热化学NPs作为NSCLC的可行治疗选择具有巨大的潜力。
    This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An \"all-in-one\" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.
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  • 文章类型: Journal Article
    已经提出了许多不同类型的纳米颗粒用于肿瘤靶向治疗。然而,大多数系统是通过一系列复杂的过程制备的,甚至无法克服血液免疫屏障。为了癌症的准确诊断和有效治疗,本文提出了用于癌症治疗的脂质胶束结构捕获量子点(QD)。使用简单的自组装程序制备QD/脂质胶束(QDM),然后与抗表皮生长因子受体(EGFR)抗体偶联以靶向肿瘤。作为治疗剂,将Bcl2siRNA-胆固醇缀合物加载到QDM的表面。所谓的免疫QDM/siBcl2(iQDM/siBcl2),在培养物以及小鼠异种移植物中表现出更有效的QD和siBcl2靶向人结直肠癌细胞的递送。iQDM/siBcl2的有效体内靶向导致更增强的siBcl2对小鼠中的靶癌症的治疗功效。根据结果,抗EGFRQDM捕获治疗性siRNA可作为肿瘤靶向治疗的替代方法.
    Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.
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  • 文章类型: Journal Article
    由于在大多数生物系统中不存在氟,氟磁共振成像(19F-MRI)在生物医学应用中特别有前途。然而,由于缺乏具有高氟含量和合适的松弛性能的安全水溶性显像剂,其使用受到限制。我们报告了基于由疏水烷基链和亲水树突组成的两亲性树枝状聚合物自组装的超分子树枝状聚合物的创新19F-MRI试剂。具体来说,这种两亲性树枝状聚合物带有多个带负电荷的末端,氟含量高,通过静电排斥有效防止氟化实体的分子内和分子间聚集。这允许高的氟核迁移率以及良好的水溶性以及用于19F-MRI的有利的弛豫特性。重要的是,自组装19F-MRI试剂能够封装近红外荧光(NIRF)试剂DiR和抗癌药物紫杉醇,用于胰腺癌的多模态19F-MRI和NIRF成像和治疗,一种致命的疾病,目前还没有足够的早期检测方法或有效的治疗方法。对小鼠中人类胰腺癌异种移植物的19F-MRI和多模态19F-MRI和NIRF成像研究证实了两种成像方式对肿瘤进行特异性成像的能力,并证明了治疗诊断药物在癌症治疗中的功效。在很大程度上优于临床抗癌药物紫杉醇。因此,这些树枝状分子纳米系统构成了有前途的19F-MRI试剂,用于有效的癌症管理。这项研究为19F-MRI试剂和治疗药物的构建提供了广阔的途径,利用自组装超分子树枝状聚合物化学。
    Fluorine magnetic resonance imaging (19F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19F-MRI. Importantly, the self-assembling 19F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19F-MRI and multimodal 19F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry.
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  • 文章类型: Journal Article
    近年来,PD-L1主要用作癌症免疫疗法中的免疫检查点标记。然而,由于肿瘤的异质性,这种疗法的反应率往往低于预期.除了它在免疫治疗中的作用,PD-L1作为肿瘤细胞表面的特异性靶标用于靶向诊断和治疗干预。目前还没有完全开发的PD-L1靶向临床诊断和治疗探针。这限制了该靶标的探索和临床开发。
    在这项研究中,我们利用有机黑色素纳米颗粒设计了一种具有多模式成像和双重治疗功能的PD-L1靶向探针.用WL12-SH肽的官能化使纳米探针具有特异性靶向能力。随后用89Zr进行放射性标记(半衰期:100.8小时)和Mn2离子的螯合使探针具有同时进行PET和MRI成像方式的能力。细胞摄取测定显示出明显的特异性,阳性细胞的摄取明显高于阴性细胞(p<0.05)。双模态PET/MRI成像描绘了肿瘤部位的快速和持续积累,注射后24小时,PET和MRI的肿瘤与非肿瘤(T/NT)信号比分别为16.67±3.45和6.63±0.64,分别。我们将治疗性放射性核素131I(半衰期:8.02天)与构建体结合,并联合低剂量放疗和光热治疗(PTT),最终获得优异的抗肿瘤疗效,同时保持高安全性。与对照组和单一疗法组相比,接受双模式疗法的队列中的肿瘤显示出体积和重量显着降低。
    我们开发并应用了一种新型靶向多模态热疗纳米探针,其特点是其高特异性和优越的成像能力,如PET/MRI模式。此外,当与PTT联合使用时,这种纳米探针可在较低的放射性核素剂量下获得有效的治疗效果.
    UNASSIGNED: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target.
    UNASSIGNED: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67±3.45 for PET and 6.63±0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups.
    UNASSIGNED: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT.
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  • 文章类型: Journal Article
    现有药物的再利用,被称为治疗,对精准医学产生了深远的影响。吲哚菁绿(ICG),一种成熟的临床染料,一直是明星特工,描述为具有并发光或声敏感能力和共同递送可及性的多功能分子,在各种疾病的单峰或多模态成像引导治疗领域显示出巨大的潜力,导致对立即临床翻译的广泛考虑。在这次审查中,我们努力通过澄清ICG的特征和适用性之间的关系,将对ICG绩效评估重新利用的理解付诸实践。具体来说,我们解决了在制定ICG重新利用战略过程中遇到的障碍,以及在ICG重新利用领域取得的值得注意的进展。我们还详细介绍了含有ICG的药物的结构-功能相关性以及不同结构基团如何显着影响理化性质。
    The repurposing of existing drugs, referred to as theranostics, has made profound impacts on precision medicine. Indocyanine green (ICG), a well-established and clinical dye, has continued to be a star agent, described as a multifunctional molecule with concurrent photo- or sono-sensitiveness capabilities and co-delivery accessibility, showing remarkable potential in the area of unimodal or multimodal imaging-guided therapy of various diseases, leading to the extensive consideration of immediate clinical translations. In this review, we strive to bring the understanding of repurposing performance assessment for ICG into practice by clarifying the relationships between its features and applicability. Specifically, we address the obstacles encountered in the process of developing an ICG repurposing strategy, as well as the noteworthy advancements made in the field of ICG repurposing. We also go into detail about the structure-function correlations of drugs containing ICG and how different structural groups significantly affect the physicochemical properties.
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