The diagnosis of hepatic fibrosis by magnetic resonance and near-infrared imaging using dual-modality nanoparticles

Hepatic fibrosis (HF), as the only reversible process of chronic liver disease, remains a big diagnostic challenge. Development of noninvasive and effective methods to assess quantitatively early-stage HF is of great clinical importance. Compared with conventional diagnostic methods, near-infrared fluorescence imaging (NIR) and magnetic resonance imaging (MRI) could offer highly sensitive and spatial resolution signals for HF detection. However, precise detection using contrast agents is not possible. Superparamagnetic iron oxide (SPIO) nanoparticles have low toxicity, high sensitivity and excellent biocompatibility. Integration of Fe₃O₄ nanoparticles and indocyanine green (ICG), coupled with targeting ligand of integrin α_vβ₃, arginine–glycine–aspartic acid (RGD) expressed on hepatic stellate cells (HSCs), were used to detect HF. Both in vivo and in vitro results showed that the SPIO@SiO₂–ICG–RGD had high stability and low cytotoxicity. The biodistribution of SPIO@SiO₂–ICG–RGD was significantly different between mice with HF and healthy controls. SPIO@SiO₂–ICG–RGD was characterized and the results of imaging in vitro and in vivo demonstrated the expression of integrin α_vβ₃ on activated HSCs. These data suggest that our SPIO@SiO₂–ICG–RGD probe could be used for the diagnosis of early-stage HF. This new nanoprobe with a dual-modality imaging approach holds great potential for the diagnosis and classification of HF.

Schematic diagram for the synthesis of SPIO@SiO₂–ICG–RGD.     

Nitroxide radical-modified CuS nanoparticles for CT/MRI imaging-guided NIR-II laser responsive photothermal cancer therapy

Herein, we reported nitroxide radical-modified CuS nanoparticles (CuS–NO˙ NPs), and they exhibited a typical absorption peak at 1182 nm. Due to such a long wavelength absorbance, CuS–NO˙ NPs exhibited excellent therapeutic outcome and low damage to normal tissues. Besides, we simultaneously achieved CuS–NO˙ NPs for MRI and CT dual-modal imaging, which successfully provided a new strategy for imaging-guided tumor treatment, thus increasing potential clinical applications for cancer treatment.

Herein, we reported nitroxide radical-modified CuS nanoparticles (CuS–NO˙ NPs), and they exhibited a typical absorption peak at 1182 nm.     

OBP-functionalized/hybrid superparamagnetic nanoparticles for Candida albicans treatment

Infections caused by the opportunistic yeast Candida albicans are one of the major life threats for hospitalized and immunocompromised patients, as a result of antibiotic and long-term antifungal treatment abuse. Odorant binding proteins can be considered interesting candidates to develop systems able to reduce the proliferation and virulence of this yeast, because of their intrinsic antimicrobial properties and complexation capabilities toward farnesol, the major quorum sensing molecule of Candida albicans. In the present study, a hybrid system characterized by a superparamagnetic iron oxide core functionalized with bovine odorant binding protein (bOBP) was successfully developed. The nanoparticles were designed to be suitable for magnetic protein delivery to inflamed areas of the body. The inorganic superparamagnetic core was characterized by an average diameter of 6.5 ± 1.1 nm and a spherical shape. Nanoparticles were functionalized by using 11-phosphonoundecanoic acid as spacer and linked to bOBP via amide bonds, resulting in a concentration level of 26.0 ± 1.2 mg bOBP/g SPIONs. Finally, both the biocompatibility of the developed hybrid system and the fungistatic activity against Candida albicans by submicromolar OBP levels were demonstrated by in vitro experiments.

Hybrid superparamagnetic nanoparticles functionalized with odorant binding proteins for Candida albicans treatment.     

Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect

There is no therapy currently available for fully repairing articular cartilage lesions. Our laboratory has recently developed a visible light‐activatable methacrylated gelatin (mGL) hydrogel, with the potential for cartilage regeneration. In this study, we further optimized mGL scaffolds by supplementing methacrylated hyaluronic acid (mHA), which has been shown to stimulate chondrogenesis via activation of critical cellular signalling pathways. We hypothesized that the introduction of an optimal ratio of mHA would enhance the biological properties of mGL scaffolds and augment chondrogenesis of human bone marrow‐derived mesenchymal stem cells (hBMSCs). To test this hypothesis, hybrid scaffolds consisting of mGL and mHA at different weight ratios were fabricated with hBMSCs encapsulated at 20 × 10⁶ cells/ml and maintained in a chondrogenesis‐promoting medium. The chondrogenenic differentiation of hBMSCs, within different scaffolds, was estimated after 8 weeks of culture. Our results showed that mGL/mHA at a 9:1 (%, w/v) ratio resulted in the lowest hBMSC hypertrophy and highest glycosaminoglycan production, with a slightly increased volume of the entire construct. The applicability of this optimally designed mGL/mHA hybrid scaffold for cartilage repair was then examined in vivo. A full‐thickness cylindrical osteochondral defect was surgically created in the rabbit femoral condyle, and a three‐dimensional cell–biomaterial construct was fabricated by in situ photocrosslinking to fully fill the lesion site. The results showed that implantation of the mGL/mHA (9:1) construct resulted in both cartilage and subchondral bone regeneration after 12 weeks, supporting its use as a promising scaffold for repair and resurfacing of articular cartilage defects, in the clinical setting.     

SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy

Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r₂ value can be enhanced from 164 to 208 (s^− 1 mM^− 1 Fe) by increasing the SPIO concentration from 14.1 to 28.2 mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy.     

A simple method for the synthesis of hyaluronic acid coated magnetic nanoparticles for highly efficient cell labelling and in vivo imaging

Highly stable colloidal hyaluronic acid coated magnetic nano-particles were prepared via a ligand exchange method. These particles exhibited excellent cell labeling efficiencies and superior potential as MRI contrast agents, which are useful to target tumor cells expressing hyaluronic acid receptors such as CD44.     

"适配子-PLGA纳米粒"靶向超声/光声相变造影剂的制备

目的 研制一种适配子偶联的包裹纳米金棒和液态氟碳的PLGA纳米粒。方法 采用双乳化法制备包裹纳米金棒及全氟己烷(PFH)的PLGA纳米粒(GNP);用碳二亚胺法将适配子与PLGA纳米粒连接获得"适配子-PLGA纳米粒"靶向相变造影剂(AP-GNP)。光镜、激光共聚焦显微镜及电镜下观察及检测AP-GNP基本性质;激光共聚焦显微镜下及流式细胞术观察及检测适配子与纳米粒连接情况;以激光仪辐照AP-GNP观察其光致相变情况;观察AP-GNP与乳腺癌细胞MCF-7特异性结合情况。结果 成功制备适配子修饰的包裹纳米金棒和PFH的PLGA纳米粒, 其平均粒径为(472.43±25.82)nm, 适配子与纳米粒的连接率为达97.98%;激光辐照AP-GNP后, 光致相变效果明显;AP-GNP粘附于MCF-7细胞周围, 未修饰适配子GNP未见明显特异性结合。结论 成功制备偶联的包裹纳米金棒和PFH的PLGA纳米粒, 其光致相变效果明显, 靶向性能良好。     

纳米微粒在分子成像中的研究进展

近年来纳米技术在分子成像方面的应用研究发展很快,纳米微粒的发展出现多元化的显像模式.这些纳米级标志可以用于生物体内特异性细胞和组织的成像,一些纳米微粒对于监测人类疾病的生物过程及评价治疗效果可能有重要作用.尽管很多研究还处于实验阶段,但其潜力却非常大.     

Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry

For effective and safe thermotherapy, real-time, accurate, three-dimensional tissue thermometry is required. Magnetic resonance imaging (MRI)-based thermometry in combination with current temperature responsive contrast agents only provides an 'off-on' signal at a certain temperature, not indicating temperature increases beyond the desired therapeutic levels. To overcome this limitation, a novel Gd-chelated hydrogel-lipid hybrid nanoparticle (HLN) formulation was developed that provides an 'off-on-off' signal defining a thermometric window for MR thermometry. Novel thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (NIPAM-co-AM) hydrogel nanoparticles (<15 nm) with bisallylamidodiethylenetriaminetriacetic acid, a novel crosslinker with Gd(3+) chelation functionality, were synthesized. The Gd-hydrogel nanoparticles were encapsulated in a solid lipid nanoparticle matrix that prevented T(1)-weighted contrast signal enhancement. Melting of the matrix lipid freed the Gd-hydrogel nanoparticles into the bulk water and an 'off-on' contrast signal enhancement occurred. As the temperature was further increased to temperatures greater than, the volume phase transition temperature of the hydrogel nanoparticles, they collapsed and provided an 'on-off' signal diminution. Both the 'off-on' and the 'on-off' transition temperature could be tailored by changing the lipid matrix and altering the NIPAM/AM ratio in the hydrogel, respectively. This allowed MRI thermometry of different temperature windows using the Gd-HLN system.     

Functionalization of theranostic AGuIX® nanoparticles for PET/MRI/optical imaging

A novel trifunctional imaging probe containing a chelator of radiometal for PET, a NIR heptamethine cyanine dye, and a bioconjugatable handle, has been grafted onto AGuIX® nanoparticles via a Michael addition reaction. The resulting functionalized nanoparticles have been fully characterized, radiolabelled with ⁶⁴Cu, and evaluated in a mice TSA tumor model using multimodal (PET/MRI/optical) imaging.

The controlled dual functionalization of AGuIX® nanoparticles afforded trimodal imaging (PET/MRI/fluorescence) theranostic agents.

The design of multi-modal contrast agents has become one of the thrust areas of research in molecular imaging science.^1,2 Combination of two imaging modalities can be really advantageous if they complement each other in revealing the correct biological information for preclinical and clinical use. This approach has given rise to hybrid imaging modalities like PET/MRI, SPECT or PET/CT, or PET/OI. Hybrid imaging helps in retrieving the information that otherwise would not be available with individual modality. For instance, the combination of functional information (from PET) and anatomic/spatial information (obtained by CT or MRI) into a single image provides a more accurate diagnostic.^3,4 Combining nuclear and optical imaging also represents a valuable approach.^5–7 Indeed, PET or SPECT whole-body scan may allow diagnosis and staging of patients, whereas optical imaging can be used for intra-operative surgical assistance. To successfully leverage such symbiosis, it is necessary to develop tracers that can have dual/multiple functionality. Nanoparticles represent a class of materials that are well suited to such purpose as they exhibit intrinsic imaging and/or therapeutic properties and they can be easily functionalized to add other modalities.^8–10 Among promising nanomaterials, AGuIX® are particularly attractive. These sub-5 nm nanoparticles, firstly described in 2011,¹¹ are composed of a polysiloxane matrix on which DOTAGA–Gd complexes are covalently bound. AGuIX® nanoparticles have already shown their therapeutic efficiency as radiosensitizers on different in vivo preclinical models of cancer: glioblastoma, brain metastases, melanoma, pancreatic cancer, liver cancer, head and neck cancer and lung cancer.¹² They have been recently translated to the clinic, for the treatment of multiple brain metastases and for cervix cancer in association with radiation therapy.¹² New generations of AGuIX® nanoparticles have been developed by functionalization of their surface, for example by addition of ⁶⁸Ga¹³ or ⁸⁹Zr¹⁴ chelators for PET/MRI imaging.Here we report a method for the dual functionalization of AGuIX® nanoparticles with both a macrocyclic chelator optimized for the complexation of a PET radioisotope (⁶⁴Cu or ⁶⁸Ga) and a NIR heptamethine cyanine dye. Owing to the intrinsic properties of the pristine AGuIX® nanoparticles, the resulting nano-object is a theranostic nanoparticle that can be tracked in vivo using three different imaging modalities, i.e., PET, MR and optical imaging. Our strategy relies on the use of a monomolecular multimodal imaging probe (MOMIP) which contains within one single molecule: (i) a chelating agent (in this case a NODAGA moiety which has become in the last years a chelator of choice for ⁶⁴Cu and ⁶⁸Ga),^15,16 (ii) a Cy-7 derivative (known as IR-783, and bearing a reactive meso-chlorine atom),^17,18 (iii) a reactive handle for grafting the MOMIP to the surface of the nanoparticles (here a maleimide group). The use of such MOMIP for appending different imaging reporters to the nanoparticle is highly beneficial when compared to the sequential grafting of the two different probes, which can present many process and characterization related challenges. Indeed, our approach allows a better control of the chemical composition of the resulting nano-objects, in particular the ratio of the two probes, and enables a better reproducibility of the synthesis. Several MOMIP containing BODIPY and DOTA derivatives have been developed by our group and conjugated to various biomolecules such as peptides,¹⁹ monoclonal antibodies,²⁰ or lipopolysaccharides,²¹ providing proofs of concept of such strategy for dual SPECT/optical imaging.The development of the desired MOMIP entails a multistep chemical synthesis with series of coupling and deprotection steps. In a typical MOMIP synthesis, the bioconjugatable handle is introduced at the last step, because of its sensitivity and reactivity. In the synthetic strategy described herein, we also wanted to consider if it was possible to introduce more stable functions such as maleimide earlier, and in particular in the first step of the synthesis. This strategy is particularly valuable when working with sensitive fluorophores such as polymethine cyanine dyes which could then be introduced in the very last step. This approach was successful, and the MOMIP IR-783-Lys(Mal)NODAGA (6) could be obtained as depicted in Fig. 1A. The lysine derivative 1, obtained almost quantitatively by coupling 6-maleimidohexanoic acid to the commercially available Boc-Lys-OH was linked to the bifunctional chelating agent 2via the intermediate N-hydroxysuccinimidyl (NHS) ester formation, yielding compound 3 in 55% yield. Compound 4 was then obtained by single step deprotection of both the tert-butyl ester and Boc protecting groups of chelator and lysine units, using TFA. The final MOMIP IR-783-Lys(Mal)NODAGA (6) could be synthesized via the amide coupling of 4 and dye 5, easily obtained through nucleophilic substitution of the chlorine atom at the meso position of IR-783 by 6-mercaptohexanoic acid.Open in a separate windowFig. 1(A) Synthesis of MOMIP IR-783-Lys(Mal)NODAGA 6. (B) Functionalization of AGuIX® with MOMIP 6.The surface of the AGuIX® nanoparticles possesses primary amino groups that stem from the APTES (3-aminopropyltriethoxysilane) reagent that is used in the synthetic process. In order to generate thiol groups at the surface of the nanoparticles, able to react with the maleimide moiety of the MOMIP 6, nanoparticles were thiolated with Traut''s reagent at pH 8 for 1 h (Fig. 1B). After purification by ultrafiltration cycles, the sulfhydryl-functionalized AGuIX® nanoparticles were characterized by Ellman''s assay to determine the number of thiol groups appended, which was found to be around 2.5 per nanoparticle. This degree of thiolation was considered optimal for further conjugation as excessive thiolation might potentially cause nanoparticles to clump by inter-particulate disulfide bridging. The purified thiolated nanoparticles were immediately treated with the MOMIP 6 at pH 7, at room temperature and protected from light. In these conditions, the thiol–maleimide coupling proceeded quickly to form a stable thioether linkage.The functionalized AGuIX-NODAGA-IR783 nanoparticles were characterized using various analytical techniques (

Design of poly-epsilon-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery.

This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.     

Polydopamine-doped virus-like structured nanoparticles for photoacoustic imaging guided synergistic chemo-/photothermal therapy

The therapeutic diagnosis effect of cancer commonly depends on the cellular uptake efficiency of nanomaterials. However, the morphology of nanomaterials significantly affects cellular uptake capability. Herein, we designed a polydopamine-doped virus-like structured nanoparticle (GNR@HPMO@PVMSN) composed of a gold nanorod (GNR) core, hollow periodic mesoporous organosilica (HPMO) shell and polydopamine-doped virus-like mesoporous silica nanoparticle (PVMSN) outer shell. Compared with conventional gold nanorod@hollow periodic mesoporous organosilica core–shell nanoparticles (GNR@HPMO), GNR@HPMO@PVMSN with its virus-like structure was proved to enhance the efficiency of cellular uptake. GNR@HPMO@PVMSN with the virtues of high photothermal conversion efficiency and good photoacoustic imaging (PAI) ability was expected to be a promising nanotheranostic agent for imaging guided cancer treatment. The experiments in vitro and in vivo proved that GNR@HPMO@PVMSN had good biocompatibility as well as photothermal conversion ability. In addition, DOX loading and pH-/NIR-response DOX release abilities of GNR@HPMO@PVMSN were also verified in vitro. Therefore, the GNR@HPMO@PVMSN offers a promising strategy for PAI directed synergistic chemo-/photothermal therapy, which improves the therapeutic effect of the nanomaterial on tumors. This work explores the effects of rough surfaces on cellular uptake and provides a versatile theranostic platform for biomedical applications.

The therapeutic diagnosis effect of cancer commonly depends on the cellular uptake efficiency of nanomaterials.     

一体化PET/MR颅脑成像检查规范(2017版)

一体化PET/MR已经逐渐在临床应用,其检查流程的规范化是需要迫切解决的重大任务。一体化PET/MR颅脑检查规范的主要内容包括临床适应证及禁忌证、扫描前准备、扫描规范（PET扫描、常规颅脑MR扫描、不同颅脑疾病的特殊MR扫描）、放射性示踪剂和MR对比剂的使用注意事项。制定该操作规范的目的是为临床工作中处理不同颅脑疾病,提供针对性的PET/MRI检查操作规范。本规范在PET显像剂方面,仅限于¹⁸F-FDG。     

In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles

Multidrug resistance (MDR) is a significant problem in the clinical management of several cancers. Overcoming MDR generally involves multi-modal therapeutic approaches that integrate enhancement of delivery efficiency using targeted nano-platforms as well as strategies that can sensitize cancer cells to drug treatments. We recently demonstrated that tandem delivery of siRNAs that downregulate anti-apoptotic genes overexpressed in cisplatin resistant tumors followed by therapeutic challenge using cisplatin loaded CD44 targeted hyaluronic acid (HA) nanoparticle (NP) induced synergistic antitumor response CD44 expressing tumors that are resistant to cisplatin. In the current study, a near infrared (NIR) dye-loaded HA NP was employed to image the whole body localization of NPs after intravenous (i.v.) injection into live mice bearing human lung tumors that were sensitive and resistant to cisplatin. In addition, we quantified the siRNA duplexes and cisplatin dose distribution in various tissues and organs using an ultra-sensitive quantitative PCR method and inductively coupled plasma-mass spectrometry (ICP-MS), respectively, after i.v. injection of the payload loaded HA NPs in tumor bearing mice. Our findings demonstrate that the distribution pattern of the siRNA and cisplatin using specifically engineered CD44 targeting HA NPs correlated well with the tumor targeting capability as well as the activity and efficacy obtained with combination treatments.     

Folic acid-conjugated gold nanorod@polypyrrole@Fe3O4 nanocomposites for targeted MR/CT/PA multimodal imaging and chemo-photothermal therapy

Integrating multimodal bioimaging and different therapies into one nanoplatform is a promising strategy for biomedical applications, but remains a great challenge. Herein, we have synthesized a biocompatible folic acid (FA) functionalized gold nanorod@polypyrrole@Fe₃O₄ (GNR@PPy@Fe₃O₄-FA) nanocomposite through a facile method. The conjugated FA has endowed the nanocomposite with the ability to recognize targeted cancer cells. Importantly, the nanocomposite has been successfully utilized for magnetic resonance (MR), computed tomography (CT) and photoacoustic (PA) multimodal imaging. Moreover, the GNR@PPy@Fe₃O₄-DOX nanocomposite shows pH-responsive chemotherapy and enables the integration of photothermal therapy and chemotherapy to achieve superior antitumor efficacy. The GNR@PPy@Fe₃O₄-DOX nanocomposites have a drug release of 23.64%, and the photothermal efficiency of the GNR@PPy@Fe₃O₄ nanocomposites reaches 51.46%. Cell viability decreases to 15.83% and 16.47% because of the combination of chemo-photothermal therapy effects. Moreover, the GNR@PPy@Fe₃O₄-DOX-FA nanocomposite could target cancer cells via folic acid and under a magnetic field. The in vivo multimodal imaging and chemo-photothermal therapy effects showed that the GNR@PPy@Fe₃O₄-DOX-FA nanocomposites are a good contrast and theranostic agent. Thus, this multifunctional nanocomposite could be a promising theranostic platform for cancer diagnosis and therapy.

Folic acid-conjugated gold nanorod@polypyrrole@Fe₃O₄ nanocomposites can be used for targeted MR/CT/PA multimodal imaging and chemo-photothermal therapy.     

Design and production of hybrid nanoparticles with polymeric-lipid shell–core structures: conventional and next-generation approaches

Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the natural biocompatible polymer chitosan to achieve stable shell–core nanostructures. Covered nanoliposomes were produced using an innovative continuous method based on microfluidic principles. The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties, size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method were compared with those of the conventional dropwise method and the obtained products. The proposed simil-microfluidic method led to the production of stable and completely chitosan-covered liposomes with a shell–core nanostructure that avoided the disadvantages inherent in the conventional method (which are time-consuming and/or require bulky and more expensive equipment).

An innovative, simil-microfluidic, nanoliposome-covering method operating continuously with massive production yield overcoming the disadvantages of conventional methods is proposed.     

超声响应性纳米粒子用于超声/光声成像引导下声动力/饥饿治疗小鼠结直肠癌

目的 制备载四苯基卟啉锌(TPZ)、葡萄糖氧化酶(GOD)与全氟戊烷的超声响应性纳米粒子(NP)TPZ-GOD NP,并评估其超声/光声双模态成像效果及介导声动力治疗(SDT)联合饥饿治疗小鼠结直肠癌的效果.方法 以薄膜水化法制备载TPZ及GOD的NP.观察TPZ-GOD NP基本特性,以紫外分光光度计检测其超声辐照下...     

Dual-response CuS@MnO2 nanoparticles with activatable CT/MR-enhanced in vivo imaging guided photothermal therapy

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO₂ coating, were employed for diagnosing and treating tumors. After reacting with an RGD peptide, the nanoparticles were able to target and focus on tumor sites. Once the nanoparticles were enriched in tumors by RGD targeting, the MnO₂ coating decomposed to Mn²⁺ ions in the tumor microenvironment. Meanwhile, the decomposition of MnO₂ allowed the dispersion of aggregated CuS NPs to enter deep tumors, and a 1064 nm laser with powerful penetration was utilized to activate CuS NPs in deep tumors for PTT. More importantly, the generated Mn²⁺ ions were used for stimuli-enhanced T₁-weighted magnetic resonance imaging (T₁-MRI) and agminated CuS NPs in tumors were accepted for computed tomography (CT) imaging. It was found that these nanocomposites can accurately indicate tumor sites after being intravenously injected, and in vitro and in vivo experiments illustrated the tremendous potential of these nanoplatforms for use in imaging-guided PTT against HepG2 tumors.

A stable multifunctional nanoplatform with superior biocompatibility and excellent targeting function was synthesized for MR/CT image guided PTT treatment, for potential application in clinical cancer treatment.     

Thermal behavior and combustion of Al nanoparticles/ MnO2-nanorods nanothermites with addition of potassium perchlorate

To explore the effect of potassium perchlorate (KClO₄) on Al nanoparticles/MnO₂-nanorods nanothermite systems, in this paper, Al/MnO₂ nanothermites with different mass fraction of KClO₄ were prepared by electrospray. The samples were characterized by XRD, SEM, TG-DSC analysis. According to the results of TG-DSC, the addition of KClO₄ seemed to cause no direct improvement on their exothermic reactions. But the results of activation energy calculations showed that KClO₄ could remarkably reduce the activation energy of nanothermite systems by up to 48.8%. The XRD results indicated that residues consisted mainly of Mn₃O₄. The reasons why KClO₄ has little effect on thermal properties but makes a great difference on kinetics were analyzed and discussed. Finally, onset combustion tests were carried out. The results and findings provide a useful approach to decrease the activation energy and combustion rate of nanothermites, which may facilitate practical and combustible applications.

To explore the effect of potassium perchlorate (KClO₄) on Al nanoparticles/MnO₂-nanorods nanothermite systems, in this paper, Al/MnO₂ nanothermites with different mass fraction of KClO₄ were prepared by electrospray.     

Low radiation dose imaging of myocardial perfusion and coronary angiography with a hybrid PET/CT scanner

Objectives: To test the image quality and feasibility of a sequential low radiation dose protocol for hybrid cardiac PET/CT angiography (CTA). Background: Multidetector computed tomography (MDCT) is a non‐invasive method for coronary angiography. The negative predictive value of MDCT is high but perfusion imaging has a role in detecting functional significance of coronary lesions. This has encouraged combining these techniques. However, radiation dose is of concern. We report our first experiences with a low dose sequential CTA mode applicable to hybrid imaging. Methods: In the first phase, 10 consecutive cardiac MDCT angiographies were performed with spiral acquisition and compared in terms of image quality and dose with the following 10 patients performed with a new sequential mode. In the second phase, feasibility and radiation dose of a combined ¹⁵O‐water rest‐stress PET perfusion/sequential CTA protocol were assessed in another group of 61 consecutive patients. Results: Mean effective radiation dose was 60% lower in the sequential group than in the spiral group (19·3 versus 7·6 mSv, P<0·001). In the second phase, the new sequential hybrid protocol proved possible in 87% of the patients given the preconditions determined by the manufacturer. Mean effective dose of the CT acquisition was 7·6 mSv and total dose from the PET/CTA hybrid study 9·5 mSv. Conclusion: Low dose PET/CT allows cardiac hybrid studies with <10 mSv. The protocol can be applied to almost nine out of 10 patients with CT image quality comparable to spiral acquisition.