功能化载药黑磷纳米片的制备表征及抗骨肉瘤活性评价

目的：制备可稳定分散的载药纳米黑磷,并将其用于光热/化疗协同的纳米制剂。方法：采用液相剥离法,以N-甲基吡咯烷酮（NMP）为剥离剂,聚乙二醇二胺（H₂N-PEG-NH₂）、壳聚糖（CS）及A型明胶（Gel）为修饰剂,筛选并载带化疗药物盐酸阿霉素（DOX）制备出分散性良好的载药黑磷纳米片。通过透射电镜、傅立叶变换红外光谱仪及流式细胞仪等仪器,进行形貌结构表征及体外细胞学评价。结果：剥离方法筛选试验表明BPNSs最佳制备工艺为：水浴超声300 W,10 h,探头超声180 W,6 h,温度<30℃,表现出外观形貌均一;修饰剂筛选试验表明H₂N-PEG-NH₂/BPNSs质量比为10：1,BPNSs/DOX质量比为1：1,表现出良好的稳定性及负载率;体外释放试验表明,DOX在弱酸性条件下结合近红外光照（NIR）释放迅速,展现出光控释药特性;体外细胞学试验表明PEG-BPNSs-DOX具有良好的抗骨肉瘤活性。结论：PEG-BPNSs-DOX可稳定分散,制备简单,具有NIR光控释药特性及良好的光热性能,有利于光热/化疗协同治疗骨肉瘤,在纳米递送系统中具有广阔应用前景。     

壳聚糖递送系统在肿瘤光热治疗中的应用和进展

肿瘤持续侵袭着人类健康,光热治疗作为一种肿瘤治疗的新方法受到越来越多的关注和研究。壳聚糖是一种天然来源丰富的阳离子多糖,具有良好的生物相容性、可降解性、结构衍生化特性。壳聚糖及其衍生物的骨架上含有大量的氨基和羟基,可通过物理或者化学方法形成壳聚糖纳米粒、水凝胶以及涂层等多种形式的载体,装载或结合光热转换剂,在近红外激光辐射下形成局部高温抑制肿瘤细胞。本综述系统介绍了壳聚糖递送系统在肿瘤光热治疗方面的研究进展。     

靶向尿激酶型纤溶酶原激活物受体的抗肿瘤药物的研究进展

尿激酶型纤溶酶原激活物受体（uPAR）是一种糖基磷脂酰肌醇锚定的膜蛋白,已被发现在多种癌细胞中过表达,这一特性使得uPAR成为治疗癌症的一个理想靶标。目前,多种以uPAR为靶点的抗癌药物已被开发,主要包括多肽、单克隆抗体、配体靶向毒素。此外,uPAR作为靶点也已在纳米药物递送系统和光热疗法（PTT）/光动力疗法（PDT）中得到应用。因此就靶向uPAR的抗肿瘤药物的研究进展做一综述。     

多功能介孔二氧化硅纳米粒在肿瘤治疗中的研究进展

介孔二氧化硅纳米粒由于较高的物理化学稳定性、易于官能化、低毒性以及对许多不同类型治疗剂的巨大负载能力,涉及了化学药物治疗、光热治疗、光动力治疗以及联合治疗,在肿瘤治疗方面受到极大的关注和广泛的研究探索。本文介绍了近年来基于介孔二氧化硅纳米粒作为载体在肿瘤治疗方面的一些研究报道,这些智能化的多功能性已经促使介孔二氧化硅纳米粒成为将来用于临床的非常有前途的药物纳米载体。     

铋基纳米药物系统的抗肿瘤诊疗及生物安全性研究进展

纳米生物医学是生物医药领域中最具有应用前景的方向之一,无机纳米材料由于其优良的物理、化学特性、稳定的化学性质以及高生物相容性,在众多的纳米材料中脱颖而出。作为一种低成本的无机纳米材料,铋基纳米材料由于具有带隙可调、低毒性、易于功能化、较大X射线衰减系数、较高光热转换效率和长循环半衰期等优势,在癌症诊断和治疗方面具有种种潜在的用途和广阔的应用前景。本文综述了铋基纳米材料在肿瘤诊断、治疗和生物安全性方面的最新研究进展,为新一代铋基纳米药物系统的设计和开发提供理论依据和开发思路。     

基于红细胞的仿生载体用于光热剂递送和肿瘤光热治疗的研究进展

光热疗法是一种借助光热剂的光热转换特性,通过升高局部温度杀死肿瘤细胞的新型治疗手段.纳米递送系统的应用能够显著改善光热剂的稳定性和体内分布,提高光热疗法的治疗效率.但人工合成的纳米材料往往存在生物相容性差等安全性问题.以天然红细胞作为光热剂递送系统能提高生物相容性并延长体内循环时间.将红细胞膜提取并整合至纳米载体表面或...     

金纳米微粒的光热治疗及放疗增敏研究

金纳米微粒在肿瘤光热治疗、生物传感、分子影像以及基因递送等方面的研究已成为基础研究及应用研究的热点。本文将从金纳米微粒光学特性入手,讨论其在肿瘤光热治疗和放疗增敏方面的研究现状。     

载血卟啉单甲醚中空金纳米球的光热光动力联合抗肿瘤研究

目的 设计基于中空金纳米球的新型纳米给药系统(HMME-PEI-HAuNS),在近红外光照射下研究其同步光热光动力联合抗肿瘤作用。方法 以钴纳米粒为模板制备中空金纳米球(HAuNS),将血卟啉单甲醚(HMME)通过枝状聚乙烯亚胺(PEI)装载到HAuNS表面,形成纳米给药系统(HMME-PEI-HAuNS);采用核磁共振氢谱、红外光谱、紫外光谱分析对HMME-PEI-HAuNS进行结构确证。建立荷瘤(SKOV3)小鼠模型,通过荧光活体成像仪考察其体内分布情况。将对肿瘤细胞表面EphB4受体具有特异性亲和力的靶向多肽TNYL修饰于其表面以增强该纳米体系的靶向性,用核染试剂Hoechst染色SKOV3细胞,在激光共聚焦显微镜下观察细胞内的荧光强度,用MTT比色法进行细胞毒性评价。结果 HAuNS能对HMME进行成功装载,装载率达63.4±5.2%。由于肿瘤的高通透性和滞留效应(EPR 效应),HMME-PEI-HAuNS较游离HMME和HMME-PEI胶束在肿瘤部位有更多的累积量和更长的滞留时间,累计效率约为1.6%。荧光定量统计显示在TNYL多肽的介导下纳米球的靶向性更高,在808 nm激光照射下,TNYL-HMME-PEI-HAuNS发挥光热和光动力协同作用产生强大的肿瘤杀伤作用,在高浓度时,细胞存活率不到10%。结论 主动靶向纳米球(TNYL-HMME-PEI-HAuNS)在808 nm近红外光照射下具有较强的光热光动力联合抗肿瘤作用。     

纳米材料在癌症光动力治疗研究中的应用进展

纳米材料以其明确的大小、形状、组成和表面能等性能为生物分析、生物成像和治疗提供了多模式、多功能的平台。本文重点综述了多种纳米技术在光动力疗法治疗癌症方面的应用进展,包括上转换纳米粒、量子点、纳米金、碳纳米材料、二氧化硅纳米粒、脂质体和胶束纳米材料,对各种纳米材料的特点以及近些年来相关研究和发展情况进行了评述。     

pH响应性电荷反转型共聚物纳米粒的构建及其光热性能考察

利用多巴胺和5-羟色胺在碱性条件下能发生氧化自聚合反应的特性,制备了pH响应性电荷反转型共聚物纳米粒(PDH NPs)。采用透射电镜、紫外吸收光谱及红外光谱对所得纳米粒进行表征,并考察了纳米粒的pH响应性电荷反转能力及光热性能。结果表明,制备的PDH NPs呈均一的球形结构,粒径约100 nm。在体外,PDH NPs在pH 7.6条件下带负电,在pH 6.0下带正电,表现出pH响应性的电荷反转能力。PDH NPs同时具有明显的光热效应,且该光热效应具有可重复性。本研究为构建具有肿瘤靶向性及光热治疗协同抗肿瘤作用的多功能纳米载体提供了新思路。     

pH-Sensitive Black Phosphorous–Incorporated Hydrogel as Novel Implant for Cancer Treatment

In this study, black phosphorus nanosheets (BPNSs) were incorporated into a hydrogel formed from dibenzaldehyde-functionalized polymer (DF-PEG) and polyaspartylhydrazide (PAHy) polymer to create an injectable and pH-sensitive DF-PEG-PAHy/BPNSs hydrogel, which can be used as a smart depot for synergistic chemo-photothermal cancer therapy. The DF-PEG-PAHy/BPNSs hydrogel exhibited excellent gelation characteristics, pH sensitivity, and near-infrared responsiveness. The nanocomposite hydrogel provided controlled drug release and near-infrared irradiation speeded up release of drug from the hydrogel because of the photothermal effect of the BPNSs. Cytotoxicity tests confirmed that the hydrogel has good biocompatibility and exerts its photothermal effect in vitro. Antitumor tests in mice demonstrated the capacity of DF-PEG-PAHy/BPNSs hydrogel for synergistic chemo-photothermal therapy in vivo. The hydrogel showed reduced adverse effects because of stable drug release in the tumor area and an efficient photothermal effect. Together, these data demonstrated the potential of DF-PEG-PAHy/BPNSs hydrogel containing a chemotherapy drug to serve as a novel smart delivery system for combined chemo-photothermal cancer therapy.     

Trimodal synergistic antitumor drug delivery system based on graphene oxide

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π–π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4?°C in 10?min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.     

Theragnostic approaches using gold nanorods and near infrared light

Gold nanoparticles have unique optical properties such as surface-plasmon and photothermal effects. Such properties have resulted in gold nanoparticles having several clinical applications. Gold nanorods (which are rod-shaped gold nanoparticles) show a surface plasmon band in the near-infrared region. They have therefore been proposed as contrast agents for bioimaging, or as heating devices for photothermal therapy. Polyethylene glycol-modified gold nanorods systemically administrated into mice can be detected with integrating sphere, and the stability of the gold nanorods in blood flow evaluated. After intravenous injection of gold nanorods followed by near-infrared laser irradiation, significant tumor damage triggered by the photothermal effect was observed. To deliver gold nanorods to the target tissue, thermosensitive polymer gel-coated gold nanorods were prepared. After intravenous injection of the gel-modified gold nanorods and irradiation of the tumor, a larger amount of gold was detected in the irradiated tumor than in the non-irradiated tumor. This effect is due to the hydrophobic interaction between the cellular membrane or the extracellular matrix and the gel surfaces induced by the photothermal effect. Furthermore, the photothermal effect enhanced the permeability of the stratum corneum of the skin. As a result of treatment of the skin with ovalbumin and gold nanorods followed by near-infrared light irradiation, a significant amount of protein was detected in the skin. The gold nanorods therefore showed several functions as a photothermal nanodevice for bioimaging, thermal therapy, and a drug delivery system.     

Recent trends in targeted therapy of cancer using graphene oxide-modified multifunctional nanomedicines

Rapid progresses in nanotechnology fields have led us to use a number of advanced nanomaterials (NMs) for engineering smart multifunctional nanoparticles (NPs)/nanosystems (NSs) for targeted diagnosis and therapy of various diseases including different types of malignancies. For the effective therapy of any type of solid tumor, the treatment modality should ideally solely target the aberrant cancerous cells/tissue with no/trivial impacts on the healthy cells. One approach to achieve such unprecedented impacts can be fulfilled through the use of seamless multimodal NPs/NSs with photoacoustic properties that can be achieved using advanced NMs such as graphene oxide (GO). It is considered as one of the most promising materials that have been used in the development of various NPs/NSs. GO-based targeted NSs can be engineered as programmable drug delivery systems (DDSs) to perform on-demand chemotherapy combined with photonic energy for photothermal therapy (PTT) or photodynamic therapy (PDT). In the current review, we provide important insights on the GO-based NSs and discuss their potentials for the photodynamic/photothermal ablation of cancer in combination with anticancer agents.     

Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery

Importance of the field: Plasmonic nanoparticles provide a new route to treat cancer owing to their ability to convert light into heat effectively for photothermal destruction. Combined with the targeting mechanisms possible with nanoscale materials, this technique has the potential to enable highly targeted therapies to minimize undesirable side effects.

Areas covered in this review: This review discusses the use of gold nanocages, a new class of plasmonic nanoparticles, for photothermal applications. Gold nanocages are hollow, porous structures with compact sizes and precisely controlled plasmonic properties and surface chemistry. Also, a recent study of gold nanocages as drug-release carriers by externally controlling the opening and closing of the pores with a smart polymer whose conformation changes at a specific temperature is discussed. Release of the contents can be initiated remotely through near-infrared irradiation. Together, these topics cover the years from 2002 to 2009.

What the reader will gain: The reader will be exposed to different aspects of gold nanocages, including synthesis, surface modification, in vitro studies, intial in vivo data and perspectives on future studies.

Take home message: Gold nanocages are a promising platform for cancer therapy in terms of both photothermal destruction and drug delivery.     

Tailored core‒shell dual metal–organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal–organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles, with a significantly higher inhibition rate. It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.     

Enhanced tumor treatment using biofunctional indocyanine green-containing nanostructure by intratumoral or intravenous injection

Indocyanine green (ICG) is a conventional dye that can be used in clinical near-infrared (NIR) imaging, and it is also an effective light absorber for laser-mediated photothermal therapy. However, applications of ICG were limited due to its fast degradation in aqueous media and quick clearance from the body. Herein, an ICG-containing nanostructure, ICG-PL-PEG, was developed for photothermal therapy, which was self-assembled by ICG and phospholipid-polyethylene glycol (PL-PEG). Our in vitro and in vivo experiments demonstrated that ICG-PL-PEG suspension was more efficient in producing a NIR-dependent temperature increase than ICG alone, due to the increase of ICG monomers from the addition of PL-PEG to match the central wavelength of the 808 nm laser. When conjugated with integrin α(v)β(3) monoclonal antibody (mAb), ICG-PL-PEG could be selectively internalized and retained in target tumor cells. Irradiation of an 808 nm laser after intravenous administration of ICG-PL-PEG-mAb resulted in tumor suppression in mice, while ICG alone had only limited effect. This is the first time an ICG-containing nanostructure has been used through systemic administration to achieve an efficient in vivo photothermal effect for cancer treatment. Therefore, ICG-PL-PEG could be used as a fluorescent marker as well as a light-absorber for imaging-guided photothermal therapy. All the components of ICG-PL-PEG have been approved for human use. Therefore, this unique ICG-containing nanostructure has great potential in clinical applications.     

Pyropheophorbide A and c(RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy

Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-RGD was developed for targeted near-infrared photodynamic therapy. The properties of UCNP-Ppa-RGD, such as morphology, stability, optical spectroscopy and singlet oxygen generation efficiency, were investigated. The results show that covalently linked pyropheophorbide a molecule not only is stable but also retains its spectroscopic and functional properties. In vitro studies confirm a stronger targeting specificity of UCNP-Ppa-RGD to integrin α(v)β(3)-positive U87-MG cells compared with that in the corresponding negative group. The photosensitizer-attached nanostructure exhibited low dark toxicity and high phototoxicity against cancer cells upon 980 nm laser irradiation at an appropriate dosage. These results represent the first demonstration of a highly stable and efficient photosensitizer modified upconversion nanostructure for targeted near-infrared photodynamic therapy of cancer cells. The novel UCNP-Ppa-RGD nanoparticle may provide a powerful alternative for near-infrared photodynamic therapy with an improved tumor targeting specificity.