pH响应型纳米药物用于化疗-光热协同治疗肿瘤

化疗协同光热治疗(PTT)是提高肿瘤疗效的一种新型治疗方式.本研究拟合成一种亚细胞器靶向的近红外响应纳米药物Fe3 O4@PDA-TPP/S2-PEG-hyd-DOX(Fe3 O4-ATSPD)作为新的光热制剂,它可通过磁靶向增强肿瘤细胞的摄取,具有良好的光热稳定性和光热转化效率.在近红外光(NlR)照射下,光热剂多巴胺(PDA)产生光热效应,促使线粒体膜电位显著下降.同时,在内涵体/溶酶体低pH值环境下,Fe3O4-ATSPD释放偶联药物DOX进入细胞核损伤DNA,最终促使肿瘤细胞凋亡.本研究制备的纳米药物能有效整合诊断和治疗,为肿瘤治疗提供新的协同治疗策略.     

光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤

基于纳米材料的化疗-光热协同治疗是一种高效的肿瘤治疗方式, 但如何构建具有高载药量与良好光热转换性能的纳米药物依然面临挑战。本研究通过超声剥离法制备二维硼(boron, B)纳米片, 进一步在其表面原位负载超小粒径硫化铜(CuS)纳米颗粒和化疗药阿霉素(DOX), 形成B-CuS-DOX纳米药物。B-CuS具有高的DOX药物装载能力(864 mg/g)和优异的光热转化性能(在808 nm处的光热转换效率为55.8%), 同时可实现pH及近红外激光双重刺激响应而释放药物。细胞实验表明在808 nm近红外光的照射下, B-CuS-DOX展示了良好的化疗-光热协同治疗效果。本研究构建的纳米药物有望为体内肿瘤治疗提供一种有效的化疗-光热协同治疗策略。     

纳米镍/介孔二氧化硅复合材料的组装及结构和性质 Ⅰ : 纳米镍/介孔二氧化硅复合材料的制备及结构表征

利用介孔组装,可以进行纳米复合材料结构和功能设计。通过溶胶-凝胶方法,采用混合、浸泡和氢热还原工艺,获得纳米镍/介孔二氧化硅复合材料。运用DSC、XRD、XPS、TEM等手段对纳米镍/介孔二氧化硅复合材料进行表征。结果表明,纳米金属Ni颗粒的尺寸由介孔SiO₂的结构和孔径分布决定,受还原温度和成分等影响,在8~20nm范围变化,浸泡法更容易获得纳米金属颗粒均匀分布的复合材料。由于SiO₂介孔结构连通,纳米Ni表面存在氧化,纳米颗粒存在于介孔中形成壳结构。介孔二氧化硅基体中添加稀土元素Ce,有利于增强介孔基体骨架强度,限制纳米颗粒聚集长大。      

pH响应铜掺杂介孔硅纳米催化剂增强肿瘤化疗–化学动力学联合治疗的研究

化学动力学疗法(CDT)利用肿瘤细胞内源性H₂O₂与芬顿催化剂反应生成高毒性的羟基自由基(·OH),从而杀死肿瘤细胞,但内源性H₂O₂不足和纳米粒子转运效率较低导致抗癌效果不理想。本研究制备了一种分散性良好、尺寸较小的铜掺杂介孔二氧化硅(Cu-MSN),负载化疗药物阿霉素(DOX)和抗坏血酸盐(AA)后,表面经叶酸(FA)和二甲基马来酸酐(DMMA)改性的壳聚糖(FA-CS-DMMA)以及羧甲基壳聚糖(CMC)包裹,得到pH响应型靶向纳米催化剂FA-CS-DMMA/CMC@Cu-MSN@DOX/AA(缩写为FCDC@Cu-MSN@DA)。扫描电镜显示纳米粒子FCDC@Cu-MSN@DA粒径约为100nm。体外48h内Cu²⁺释放量可达80%,药物DOX释放达到57.3%。释放的AA经自氧化后产生H₂O₂,诱导Cu²⁺发生类芬顿反应,从而增强CDT。细胞实验证明, FCDC@Cu-MSN@DA联合化疗药物表现出优异...     

核壳结构羟基磷灰石/介孔二氧化硅纳米颗粒的制备及其药物释放研究

核壳纳米颗粒是一种具有独特结构和性能的复合纳米材料, 在催化、生物医学和光子晶体等领域具有重要应用前景。本工作以羟基磷灰石(HAp)纳米颗粒作为核体、十六烷基三甲基溴化铵(CTAB)作为介孔模板剂, 采用改进的Stöber包覆法制备具有介孔结构的核壳HAp@mSiO₂新型纳米颗粒。通过控制正硅酸四乙酯(TEOS)的浓度及其水解和缩合动力学, 可以有效调控HAp表面包覆的mSiO₂壳层厚度。经TEM、EDS、XRD、FT-IR及BET一系列测试可知, 制备得到的HAp@mSiO₂纳米颗粒具有比表面积大、孔径尺寸窄且分布均匀等特点。同时, 以布洛芬作为模板药物, 将制备得到的材料应用于药物释放实验, 发现该核壳材料还具有良好的药物控制性能和pH响应特性, 且可以通过改变mSiO₂壳层厚度对药物释放速率进行有效调控。     

可控合成空心多孔氧化硅纳米管/CuS体系应用于化疗-光热靶向治疗

多功能药物载体的设计合成并应用于肿瘤的联合治疗得到了研究人员的广泛关注.本文介绍了一种连接靶向基团的化疗-光热联合治疗纳米平台.首先制备了尺寸可控的平均长度为40、55和150 nm的空心多孔氧化硅纳米管,在表面修饰具有光热功能的硫化铜纳米颗粒,然后连接乳糖酸基团实现肝癌细胞靶向功能.平均长度为40 nm、修饰靶向基团的空心多孔材料显示出良好的生物相容性,且具有最大的HepG2细胞吞噬量.负载盐酸阿霉素的纳米复合材料表现出pH和808 nm近红外激光刺激响应的释放效果.将CuS光热治疗和盐酸阿霉素化疗相结合的方法在体外和体内的抑制肿瘤效果都优于单独治疗.研究结果表明,该纳米复合材料在化疗-光热联合治疗方面具有潜在的应用价值.     

静电纺有机/无机杂化纳米纤维载药体系的构建及其生物医学应用

纳米纤维具有极大的比表面积、可控的多孔二级结构等一系列优良特性,使其在环境保护、能源利用、催化剂、药物载体、组织工程支架材料等领域得到了广泛应用。通过静电纺技术制备的纳米纤维主要有有机纳米纤维、无机纳米纤维、以及有机/无机杂化纳米纤维3类。结合作者课题组之前的研究成果积累,综述了各种不同的静电纺有机/无机杂化纳米纤维载药体系的构建及其生物医学应用。着重介绍了如何将药物负载在无机纳米颗粒(埃洛石、锂皂石、羟基磷灰石、介孔二氧化硅等)的表面或内部并进而和高分子混纺形成双载体纳米载药纤维的过程和相关药物缓释机理,并探讨了有机/无机杂化纳米纤维载药体系的生物医学应用,尤其是在抗菌和抗肿瘤方面的治疗应用。文章最后对该领域的研究方向和前景作了展望。     

多级孔Ti-MOFs负载超细Pd纳米颗粒实现高效光热CO2还原(英文)

设计钛基金属有机骨架(MOF)实现高效光催化CO₂还原具有重要意义但仍极具挑战.本文发展了一种新的一步原位水蚀刻方法制备超细Pd纳米颗粒/多级孔Ti-MOFs高效光催化剂,其中水刻蚀在形成多级孔结构的同时也为Pd的锚定提供了丰富位点,进而在光还原的作用下一步实现Pd纳米颗粒在MOFs表面和内部的负载.得益于多级孔结构和超细Pd颗粒负载,Pd/hMUV-10在350℃光照下的CO产率高达65.9 mmol g^-1 h^-1,比目前最先进的MOF基催化剂高出约两个数量级,并超过大多数已报道的无机半导体基催化剂.在200℃相对温和的条件下,CO的产率也达到3.36 mmol g^-1 h^-1.在350℃的连续循环测试中,催化剂活性几乎没有衰减.理论计算表明,Pd负载可增强对CO₂的吸附和降低CO₂还原能垒,从而实现高效光热CO₂还原.本文所报道的Pd/hMUV-10催化剂有望在工业CO₂捕获和转化中得...     

掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥的制备与性能表征

骨肉瘤是一种常见的恶性骨肿瘤, 常通过手术切除进行治疗。但术后造成的骨缺损难以自愈, 残余肿瘤细胞还会增加复发可能性。本研究开发了一种用于修复骨缺损和协同治疗骨肉瘤的掺钕介孔硼硅酸盐生物活性玻璃陶瓷骨水泥。首先通过溶胶-凝胶法结合固态反应制备了可作为光热剂和药物载体的掺钕介孔硼硅酸盐生物活性玻璃陶瓷微球(MBGC-xNd), 然后将微球与海藻酸钠(SA)溶液混合制备了可同时进行光热治疗和化学治疗的可注射骨水泥(MBGC-xNd/SA)。结果表明掺Nd³⁺赋予微球可控的光热性能, 负载阿霉素(DOX)的微球显示出持续的药物释放行为。此外, 载药骨水泥的药物释放量随着温度的升高而显著增加, 说明光热疗法产生的热量可促进DOX释放。体外细胞实验结果表明, MBGC-xNd/SA具有良好的促成骨活性, 并且光热-化学联合疗法对MG-63骨肉瘤细胞起到了更显著的杀伤作用, 表现出协同效应。因此,MBGC-xNd/SA作为一种新颖的多功能骨修复材料, 在骨肉瘤的术后治疗方面具有良好的应用前景。     

氢氧化铝纳米片:结构依赖性癌症化疗药物的储运（英文）

铝盐佐剂具有极好的安全记录,是各种人类疫苗中唯一获得FDA许可的无机佐剂。据我们所知,目前尚没有关于将其用作化疗药物的递送系统、并系统阐明其结构与载药性能之间关系的研究报道。本研究采用三嵌段共聚物、通过调节反应时间合成了具有可调比表面积和孔径的氢氧化铝(AlOOH)纳米片。AlOOH纳米片的最大比表面积达470 m²/g。其负载化疗药物阿霉素的能力与材料结构密切相关:比表面积和孔径越大,负载化疗药物的量越大。负载有阿霉素的AlOOH纳米片呈现与pH有关的药物释放行为:在pH～5的低p H环境下快速释放,而在pH～7.4的近中性pH下缓慢释放。流式细胞术显示,相比于游离形式的阿霉素,负载在AlOOH纳米片上的阿霉素更易被癌细胞所吞噬。而且负载阿霉素后,与低比表面积的AlOOH纳米片相比,高比表面积的AlOOH纳米片更有利于被癌细胞摄取、诱导癌细胞凋亡和坏死。因此,本研究所合成的AlOOH纳米片有望用作化疗药物递送体系。     

Graphene Quantum Dots‐Capped Magnetic Mesoporous Silica Nanoparticles as a Multifunctional Platform for Controlled Drug Delivery,Magnetic Hyperthermia,and Photothermal Therapy

A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment. Furthermore, the MMSN/GQDs nanoparticles can efficiently generate heat to the hyperthermia temperature under an alternating magnetic field or by near infrared irradiation. More importantly, breast cancer 4T1 cells as a model cellular system, the results indicate that compared with chemotherapy, magnetic hyperthermia or photothermal therapy alone, the combined chemo‐magnetic hyperthermia therapy or chemo‐photothermal therapy with the DOX‐loaded MMSN/GQDs nanosystem exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the MMSN/GQDs multifunctional platform has great potential in cancer therapy for enhancing the therapeutic efficiency.     

Multifunctional Mesoporous Silica Nanoparticles with Thermal‐Responsive Gatekeeper for NIR Light‐Triggered Chemo/Photothermal‐Therapy

In this work, a matrix metalloproteinase (MMP)‐triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near‐infrared (NIR) photothermal‐responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal‐cleavable gatekeeper (Azo‐CD), which can be decapped by ICG‐generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor‐triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.     

Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.     

Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic–Inorganic Hybridization into Frameworks

Organic–inorganic hybrid materials aiming to combine the individual advantages of organic and inorganic components while overcoming their intrinsic drawbacks have shown great potential for future applications in broad fields. In particular, the integration of functional organic fragments into the framework of mesoporous silica to fabricate mesoporous organosilica materials has attracted great attention in the scientific community for decades. The development of such mesoporous organosilica materials has shifted from bulk materials to nanosized mesoporous organosilica nanoparticles (designated as MONs, in comparison with traditional mesoporous silica nanoparticles (MSNs)) and corresponding applications in nanoscience and nanotechnology. In this comprehensive review, the state‐of‐art progress of this important hybrid nanomaterial family is summarized, focusing on the structure/composition–performance relationship of MONs of well‐defined morphology, nanostructure, and nanoparticulate dimension. The synthetic strategies and the corresponding mechanisms for the design and construction of MONs with varied morphologies, compositions, nanostructures, and functionalities are overviewed initially. Then, the following part specifically concentrates on their broad spectrum of applications in nanotechnology, mainly in nanomedicine, nanocatalysis, and nanofabrication. Finally, some critical issues, presenting challenges and the future development of MONs regarding the rational synthesis and applications in nanotechnology are summarized and discussed. It is highly expected that such a unique molecularly organic–inorganic nanohybrid family will find practical applications in nanotechnology, and promote the advances of this discipline regarding hybrid chemistry and materials.     

Generic synthesis and versatile applications of molecularly organic-inorganic hybrid mesoporous organosilica nanoparticles with asymmetric Janus topologies and structures

Precise control over the morphology,nanostructure,composition,and particle size of molecularly organic-inorganic hybrid mesoporous organosilica nanoparticles (MONs) still remains a major challenge,which severely restricts their broad applications.In this work an efficient bridged organic group-determined growth strategy has been proposed for the facile synthesis of highly dispersed and uniform MONs with multifarious Janus morphologies,nanostructures,organic-inorganic hybrid compositions,and particle sizes,which can be easily controlled simply by varying the bridged organic groups and the concentration of bis-silylated organosilica precursors used in the synthesis.In addition,the formation mechanism of Janus MONs determined by the bridged organic group has been discussed.Based on the specific structures,compositions,and asymmetric morphologies,all the synthesized Janus MONs with hollow structures (JHMONs) demonstrate excellent performances in nanomedicine as desirable drug carriers with high drug-loading efficiencies/capacities,pH-responsive drug releasing,and enhanced therapeutic efficiencies,as attractive contrastenhanced contrast agents for ultrasound imaging,and as excellent bilirubin adsorbents with noticeably high adsorption capacities and high blood compatibilities.The developed versatile synthetic strategy and the obtained JHMONs are extremely important in the development and applications of MONs,particularly in the areas of nanoscience and nanotechnology.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.     

Dual‐Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy

Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.     

Synergized Multimodal Therapy for Safe and Effective Reversal of Cancer Multidrug Resistance Based on Low‐Level Photothermal and Photodynamic Effects

Despite the therapeutic usefulness of near‐infrared irradiation (NIR)‐induced potent photothermal effects (PTE) and photodynamic effects (PDE), they inevitably damage normal tissues, often posing threat to life when treating tumors adjacent to key organs or major blood vessels. In this study, the frequently overlooked, “weak” PTE and PDE (no killing capability) are employed to synergize chemotherapy against multidrug resistance (MDR) without impairing normal tissues. An NIR‐responsive nanosystem, gold (Au)‐nanodot‐decorated hollow carbon nanospheres coated with hyaluronic acid, is synthesized as a doxorubicin (DOX) carrier with excellent photothermal and photodynamic properties. Upon low‐level infrared irradiation, the mild heat of weak PTE moderately boosts DOX unloading, meanwhile the weak PDE moderately disturbs the P‐glycoprotein function for retaining intracellular DOX by impairing mitochondrial ATP production. These two “moderate” alterations are quantitatively and functionally sufficient to augment the efficacy of chemotherapy in reversing MDR without damaging neighboring tissue. Thus, this work creates a gold‐dot‐decorated nanocarbon spheres based nanosystem for trimodal therapy, reveals the therapeutic value of the frequently ignored weak PTE/PDE, and demonstrates that synergizing with chemotherapy to overcome drug resistance does not necessarily require potent PTE/PDE.