核酸适体偶联药物的生物偶联构建技术与应用

核酸适体被称为“化学抗体”, 具有与抗体类似或更加优异的特异性和亲和力, 可以精准地靶向靶蛋白, 与靶蛋白特异性结合. 此外, 核酸适体还具有获取简单、 合成简便、 易于进行化学修饰、 不易变性、 靶标范围广、 免疫原性低及细胞内化快等优点, 已被广泛应用于众多研究领域. 在癌症治疗领域, 核酸适体作为一种优异的靶向识别工具和药物递送载体, 可实现抗肿瘤药物的精准递送. 将核酸适体与药物分子偶联, 可通过核酸适体的靶向作用使药物分子随核酸适体共同进入靶细胞, 实现药物分子在靶细胞内的富集, 进而促进靶细胞的死亡. 近年来, 核酸适体偶联药物已成为癌症靶向治疗的前沿新兴领域, 希望通过该领域的深入研究为癌症靶向治疗领域提供新思路. 本文综合评述了以生物偶联技术构建的核酸适体偶联药物及其应用研究.     

核酸适体-纳米材料复合物用于癌症的诊断与靶向治疗研究进展

因具有独特的光、电、磁、热等优异性能,纳米材料已被广泛应用于生物分析与生物医学领域。核酸适体是一类能够高亲和力和高特异性地与靶标结合的寡核苷酸序列。将核酸适体作为识别单元与纳米材料相结合,可以构建核酸适体-纳米材料复合物。近年来,在肿瘤靶向治疗方面,核酸适体-纳米材料复合物受到了人们的广泛关注。通过纳米材料与具有特异性识别能力的核酸适体的结合,核酸适体-纳米材料复合物可以为癌症治疗提供一种更有效的、低毒副作用的新策略。本文综述了核酸适体-纳米材料复合物作为药物输送载体在癌症的特异性识别与诊断及靶向治疗方面的应用。除此之外,本文还总结了核酸适体-纳米材料复合物与其他新兴技术的有效结合从而提高选择性和癌症治疗效率的相关研究进展。     

核酸适体在癌症诊疗中的研究进展

核酸适体是通过体外筛选技术得到的可特异性结合靶标分子的单链寡核苷酸分子探针, 其表现出与抗体相当或更优异的特异性和亲和力, 且具有靶标范围广、 免疫原性低、 易于精准制备和修饰及设计灵活可控等优势. 为癌症的早期筛查、 诊断及靶向治疗提供了全新的分子工具, 在癌症诊疗领域获得了广泛的关注与应用. 本文聚焦核酸适体在癌症诊断及治疗中的应用, 对近年来取得的研究进展进行了系统性总结, 并对未来发展方向及前景进行了展望.     

基于金属纳米材料的癌症光热切除疗法

在癌症治疗中,传统的手术疗法、放射疗法和化学疗法会伤害到体内正常的组织以及带来一些其他的副作用,因此新的治疗手段,如在近红外激光中利用感光增强布光热切除疗法（PTA）已经开始被研究应用于癌症治疗.在当前新兴的纳米科学领域中,有许多相关的研究成果被认为可以作为新的纳米技术手段直接应用于癌症的检测和治疗中.光热切除疗法（PTA）的基本原理是在激光照射条件下,利用光热转换产生的高热量来破坏消除癌细胞,其中,在癌细胞位点上强的光照吸收以及高的光热转换效率是光热切除疗法（PTA）能否成功实施的关键.在贵金属纳米材料中,如金纳米颗粒和银纳米颗粒,由于他们对光具有很强的表面等离子共振吸收效应,因而他们可以在光热切除疗法（PTA）应用中有效地增强光热转换效率,而且关于金属纳米材料的结构优化以及其相关的光热转换性质的研究目前也已经有了显著的成果.在光热切除疗法中,理想的纳米金属材料应该具有下列一些特征：具有强的以及可调的表面等离子共振吸收、容易传输、毒性低以及容易与目标癌细胞结合.在这篇综合评述文章中,我们将主要讲述包括金纳米颗粒、纳米棒、纳米壳结构、纳米笼状结构以及纳米空心球结构等不同结构的金纳米材料在光热切除疗法（PTA）应用中的研究.在这些不同结构的纳米材料中,金纳米空心球由于具有较小的尺寸（30～50nm）和球状结构,以及很强的、并且半峰宽较窄的可调节的表面等离子共振效应,因此在光热切除疗法（PTA）中表现出最佳的综合性质.     

核酸适体靶向的膜蛋白识别与功能调控研究进展

膜蛋白在细胞生命活动中发挥着重要作用, 研究并调控细胞膜蛋白的结构和功能有助于阐明生命活动的基本规律, 为新型药物研发和高效疾病诊治提供研究基础. 核酸适体是一类特殊的寡核苷酸序列, 因具有特异性识别靶标的能力而被广泛用于生物传感领域. 将核酸适体与DNA纳米技术相结合, 利用DNA分子可程序化设计、 可功能化修饰等优势, 发展核酸适体靶向的膜蛋白识别与功能调控方法可为研究膜蛋白相互作用提供有力工具. 本文介绍了基于核酸适体靶向识别的DNA纳米技术在膜蛋白识别及细胞功能调控中的研究进展, 并对核酸适体靶向的膜蛋白识别及功能调控领域面临的挑战进行了分析, 对其应用前景进行了展望.     

结构精确石墨烯纳米带的水相超分子自组装及其光热转换应用

近年来,结构规则的石墨烯纳米带(GNRs)因具有可控的光、电、磁等物理性能而吸引了人们的广泛关注,但是,GNRs之间很强的π-π相互作用使其在溶剂中难以分散,严重阻碍了人们对其液相物化性能,以及对其超分子组装和潜在应用的研究。上海交通大学麦亦勇研究团队采用溶液合成法,合成了具有精确结构的GNRs,并在其边缘接枝亲水聚氧化乙烯(PEO)柔性链,获得一种新型的"rod-coil"大分子刷GNR-PEO。GNR-PEO在常用有机溶剂以及水中具有良好的分散性;在水中分散质量浓度可高达0.5mg/mL(GNR骨架质量浓度)。更有趣的是,GNR-PEO在水相中自组装成超长的一维条带或具有可控直径和螺距的弹簧状螺旋超分子结构。该超分子组装体在水中呈现近红外吸收,并能高效地将近红外光转换成热量。他们的研究不仅实现了GNRs的液相分散,极大拓宽了GNRs的研究范围,也证明了GNRs在光热转换领域的潜在应用,为GNRs在光热肿瘤治疗等领域的应用开发开辟了途径。     

核酸适体功能化的二维材料场效应晶体管传感器研究进展

二维材料场效应晶体管传感器具有可调的电学性质和高的灵敏度, 非常适合用于构建高性能的传感器, 应用于疾病诊断和环境监测等领域. 核酸适体是一种生物识别分子, 具有特异性强、 稳定性高等优势. 近年来, 核酸适体功能化的二维材料场效应晶体管传感器在医疗诊断和环境监测等领域取得了显著的研究进展. 本文综合评述了核酸适体功能化的二维材料场效应晶体管传感器的最新研究进展, 对场效应晶体管传感器的结构及传感原理进行了概括, 详细介绍了二维材料的制备方法以及核酸适体功能化器件的设计原理. 在此基础上, 对核酸适体功能化的二维材料场效应晶体管传感器在疾病诊断和环境监测领域的应用进展进行了概述, 讨论了核酸适体功能化的二维材料场效应晶体管传感器面临的一些问题和挑战, 对其发展前景进行了展望.     

多巴胺基纳米材料在生物医药中的应用

多巴胺是存在于人体内的一种儿茶酚胺类神经递质。自从研究者们发现了利用多巴胺的氧化自聚合反应制备聚多巴胺涂层的简便方法之后,多巴胺基纳米材料已经发展成为一类新兴的生物材料。多巴胺基纳米材料由于具有独特的物理化学性质,例如普适性的粘附性质、高化学反应活性、优良的生物相容性和生物降解性、以及光热转换性质,而在生物传感、药物输送、光热疗法、抗菌和组织工程等领域吸引了研究者们强烈的研究兴趣。本文综述了多巴胺基纳米材料的制备、功能化及在生物医药应用方面的最新进展。首先介绍了几种典型的多巴胺基纳米材料,并讨论影响其组装过程的因素。之后详细综述了这些材料在生物医药领域的应用,尤其是在癌症诊断和治疗方面。最后,本文提出了推进多巴胺基纳米材料临床应用需要发展的研究方向。     

基于金纳米棒的生物检测、细胞成像和癌症的光热治疗

由于金纳米棒颗粒独特的可调的表面等离子共振特性,使得金纳米棒颗粒在纳米复合材料和功能化纳米器件的构建、纳米生物技术、生物医学等领域具有广泛而重要的应用前景。本文综述了金纳米棒颗粒的生物检测、细胞成像和癌症的光热治疗方面的最新研究进展,并介绍了金纳米棒颗粒的光学性质和金纳米棒颗粒和几种主要的表面修饰方法,对金纳米棒颗粒在生物应用过程中存在的主要问题进行了讨论。     

聚多巴胺的发现、反应原理及应用

聚多巴胺发现于2007年，引起了材料表面修饰领域的广泛关注。本文首先回顾了聚多巴胺的发现过程及其形成反应机理，进而阐述了聚多巴胺在传感、癌症光热疗法、催化领域的应用现状，最后，对该领域的未来研究和应用进行了合理展望。     

Two‐Dimensional Nanomaterials for Photothermal Therapy

Two‐dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT‐based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT‐synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented.     

Two-Dimensional Nanomaterials for Photothermal Therapy

Two-dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT-based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT-synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented.     

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR–PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR–PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.     

PAA-derived gold nanorods for cellular targeting and photothermal therapy

A single-step LbL procedure to functionalize CTAB-capped GNRs via electrostatic self-assembly is reported. This approach allows for consistent biomolecule/GNR coupling using standard carboxyl-amine conjugation chemistry. The focus is on cancer-targeting biomolecule/GNR conjugates and selective photothermal destruction of cancer cells by GNR-mediated hyperthermia and NIR light. GNRs were conjugated to a single-chain antibody selective for colorectal carcinoma cells and used as probes to demonstrate photothermal therapy. Selective targeting and GNR uptake in antigen-expressing SW 1222 cells were observed using fluorescence microscopy. Selective photothermal therapy is demonstrated using SW 1222 cells, where >62% cell death was observed after cells are treated with targeted A33scFv-GNRs.     

Self‐Assembling Proteins for Design of Anticancer Nanodrugs

Inspired by the diverse protein‐based structures and materials in organisms, proteins have been expected as promising biological components for constructing nanomaterials toward various applications. In numerous studies protein‐based nanomaterials have been constructed with the merits of abundant bioactivity and good biocompatibility. However, self‐assembly of proteins as a dominant approach in constructing anticancer nanodrugs has not been reviewed. Here, we provide a comprehensive account of the role of protein self‐assembly in fabrication, regulation, and application of anticancer nanodrugs. The supramolecular strategies, building blocks, and molecular interactions of protein self‐assembly as well as the properties, functions, and applications of the resulting nanodrugs are discussed. The applications in chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, gene therapy, and combination therapy are included. Especially, manipulation of molecular interactions for realizing cancer‐specific response and cancer theranostics are emphasized. By expounding the impact of molecular interactions on therapeutic activity, rational design of highly efficient protein‐based nanodrugs for precision anticancer therapy can be envisioned. Also, the challenges and perspectives in constructing nanodrugs based on protein self‐assembly are presented to advance clinical translation of protein‐based nanodrugs and next‐generation nanomedicine.     

Recent Advances in Carbon Nanomaterials for Cancer Phototherapy

Carbon nanomaterials have received great attention from the scientific community over the past few decades because of their unique physical and chemical properties. In this minireview, we will summarize the recent progress of the use of various carbon nanomaterials in the field of cancer phototherapy. The structural characteristics of each category and the surface functionalization strategies of these nanomaterials will be briefly introduced before focusing on their therapeutic applications. Recent advances on their use in photothermal therapy, photodynamic therapy, and combined phototherapies are presented. Moreover, a few challenges and perspectives on the development of carbon nanomaterials for future theranostics are also discussed.     

Conjugated Polymer Nanomaterials for Phototherapy of Cancer

Due to the excellent properties including high specificity,low side-effect and good biocompatibility,conjugated polymer nanomaterials have been served as efficient anticancer reagents in die past decades.According to the developed anticancer systems based on conjugated polymer nanomaterials,it could be summarized into three main cancer therapy strategies:photodynamic therapy(PDT),photothermal therapy(PTT)and combination therapy.In this mini review,we provide a brief introduction to three different cancer therapy modes,their mechanisms and potential biological applications.Furthermore,some perspectives on the further development of conjugated polymer nanomaterials are proposed in the territory of anticancer precision medicine.     

Selective photothermal therapy for breast cancer with targeting peptide modified gold nanorods

In this work, we prepared polyacrylic acid (PAA) coated gold nanorods (GNRs) and then the targeting peptide modified GNRs. The biocompatibility and stability of functionalized GNRs were investigated by monitoring the surface plasmon resonance (SPR) absorption intensity. The efficacy of targeted thermal therapy can be significantly enhanced via decoration with surface-bound peptide which was obtained through phage display technology. In addition, the photothermal therapy was monitored in real time with the multi-channel function of a confocal laser scanning microscope (CLSM) coupled with an 808 nm laser. This selective photothermal therapy of GNRs is a promising candidate for phototherapeutic applications.     

A photosensitizer-loaded zinc oxide-polydopamine core-shell nanotherapeutic agent for photodynamic and photothermal synergistic therapy of cancer cells

In clinical cancer research,it is quite promising to develop multimodal synergistic therapeutic strategies.Photodynamic and photothermal synergistic therapy is a very desirable multimodal therapy strategy.Herein,we report a facile and simple method to construct a nanotherapeutic agent for photodynamic and photothermal therapy.This nanotherapeutic agent(ZnO@Ce6-PDA)is composed of a ZnO nanoparticle core,an interlayer of photosensitizer chlorin e6(Ce6)and an outer layer of polydopamine(PDA).Due to the existence of Ce6,the ZnO@Ce6-PDA can efficiently generate singlet oxygen(1O2)under 660 nm laser irradiation.Moreover,the ZnO@Ce6-PDA can serve as a photothermal agent,because of the excellent photothermal conversion efficiency of the PDA coating layer in the presence of 780 nm laser.Experiment results demonstrated that the designed nanotherapeutic agent had outstanding phototoxicity upon the combination of laser irradiation at 660 and 780 nm.Thus,our work proves that the ZnO@Ce6-PDA is a promising photodynamic/photothermal dual-modal nanotherapeutic agent for enhanced cancer therapy.     

铁掺杂的聚2-硝基-1,4-苯二胺纳米球的制备及在光热/光动力/化学动力学肿瘤治疗中的应用

肿瘤微环境(TME)的复杂性,使得单一治疗方式很难实现完全治愈。 为此,构建了一种负载吲哚菁绿(ICG)的铁掺杂的聚2-硝基-1,4-苯二胺多功能纳米球Fe-PNPD-ICG(FPIs),用于光热(PTT)/光动力(PDT)/化学动力学(CDT)的联合治疗。 在808 nm激光器照射下,ICG作为光敏剂可以产生单线态氧,铁掺杂的聚2-硝基-1,4-苯二胺纳米球作为光热剂具有36.65%的光热转换效率。 FPIs一旦内化到肿瘤内,由Fe³⁺/Fe²⁺转化引发Fenton反应产生·OH实现化学动力学治疗,反应过程中可以清除TME中过表达的谷胱甘肽(GSH),从而降低肿瘤中的抗氧化能力。 同时,产生的氧气可以改善TME中乏氧情况,增强PDT的治疗效果。 因此,FPIs是PTT/PDT/CDT联合治疗的一种理想材料,在肿瘤治疗中具有潜在的应用前景。