Extremophilic Polysaccharide for Biosynthesis and Passivation of Gold Nanoparticles and Photothermal Ablation of Cancer Cells

Extremophiles are the group of organisms that are far overlooked for exploring novel biomaterials in the field of material science and bionanotechnology. Extremophilic bacterial‐sulfated exopolysaccharide, mauran (MR), is employed for the bioreduction and passivation of gold nanoparticles (AuNps) to enhance the biocompatibility of AuNps and used for photothermal ablation of cancer cells. Here, various concentrations of MR solution are tested for the reduction of HAuCl₄ solution in the presence as well as in the absence of an external reducing agent, to produce mauran‐gold nanoparticles (MRAu Nps). These biocompatible nanocomposites are treated with cancer cell lines under in vitro conditions and NIR irradiated for complete ablation. MRAu Nps‐treated cancer cells on immediate exposure to infrared radiation from a femtosecond pulse laser of operating wavelength 800 nm are subjected to hyperthermia causing cell death. Biocompatible MR stabilization could fairly reduce the cytotoxicity caused by bare AuNps during biomedical applications. Application of a biocompatible polysaccharide from extremophilic bacterial origin for reduction and passivation of AuNps and used for a biomedical purpose is known to be first of its kind in bionanofusion studies.     

Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (∼1×10⁵ to 1×10¹⁰ W/m²). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5×10² W/m² being sufficient, provided that a total fluence of ∼30 J/cm² is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm² resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.     

金纳米星诊疗剂的光热特性及其在光热治疗和光学相干层析成像中的应用研究

为了开发一种优异的用于光热治疗和光学相干层析成像的金纳米星诊疗剂,对金纳米星的制备、光热特性以及光热治疗和光学相干层析成像中的应用进行研究.利用尖端结构增强金纳米材料的局域表面等离子体共振特性,通过种子介导法制备了多枝化的金纳米星,多尖端的结构使其具有明显的光热效果,并探究了其作为光热治疗的诊疗剂和光学相干层析成像造影...     

Synthesis,characterization, and toxicity of hollow gold nanoshells

Hollow gold nanoshells (HGN) with a diameter of 50–70 nm and tunable optical properties within the near-infrared region were synthesized from a substitution reaction using a sacrificial template, in which the morphological properties of the HGN were affected by the synthesis conditions. Using EDX line scan, the composition of the structure was determined to verify if the sacrificial template is completely consumed or residues remain after the chemical synthesis, obtaining that the final HGN structure contains about 11% of the remaining silver that showed no significant effect on the cell viability of a hNS1 cell line, but resulted as toxic on a C6 glioma cell line at high concentrations. The photothermal properties were evaluated using a NIR laser, which despite its low power showed the conversion of light into heat. This study was conducted to evaluate the potential of these nanostructures as therapeutic agents with an emphasis on toxicity.     

Rapid,Reversible Release from Thermosensitive Liposomes Triggered by Near‐Infra‐Red Light

A novel drug carrier is presented consisting of plasmonic hollow gold nanoshells (HGN) chemically tethered to liposomes made temperature sensitive with lysolipids (TSL). Continuous‐wave irradiation by physiologically friendly near‐infra‐red light at 800 nm for 2.5 min at laser intensities an order of magnitude below that known to damage skin generates heating localized to the liposome membrane. The heating increases the liposome permeability in an irradiation dose dependent, but reversible manner, resulting in rapid release of small molecules such as the self‐quenching dye carboxyfluorescein or the chemotherapeutic doxorubicin, without raising the bulk temperature. The local rise in nanoshell temperature under laser irradiation is inferred by comparing dye release rates from the TSL via bulk heating to that induced by irradiation. Laser‐irradiation of TSL enables precise control of contents release with low temperature gradients confined to areas irradiated by the laser focus. The combined effects of rapid local release and localized hyperthermia provide a synergistic effect as shown by a near doubling of androgen resistant PPC‐1 prostate cancer cell toxicity compared to the same concentration of free doxorubicin.     

Optimal design of gold nanoshells for optical imaging and photothermal therapy

Gold nanoshells are of great interest in optical imaging based on their light scattering properties and photothermal therapy due to their light absorption properties. Strong light scattering is essential for optical imaging, while effective photothermal therapy requires high light absorption. In this article, the optimal core radii and shell thicknesses of silica–gold and hollow gold nanoshells, possessing maximal light scattering and absorption at wavelengths between 700 and 1100 nm, are obtained using the Mie theory of a coated sphere. The results show that large-sized gold nanoshells of high aspect ratios (the aspect ratio is defined as the ratio of core radius to shell thickness) are the efficient contrast agents for optical imaging, while smaller gold nanoshells of high aspect ratios are the ideal therapeutic agents for photothermal therapy. From the comparison of the numerical results for silica–gold and hollow gold nanoshells, the latter are seen to offer a little superior light scattering and absorption at smaller particle size. Fitting expressions for the optimal core radii and shell thicknesses are also obtained, which can provide design guidelines for experimentalists to optimize the synthetic process of gold nanoshells.     

Near‐Infrared‐Light‐Induced Fast Drug Release Platform: Mesoporous Silica‐Coated Gold Nanoframes for Thermochemotherapy

Development of advanced theranostics for personalized medicine is of great interest. Herein, a multifunctional mesoporous silica‐based drug delivery carrier has been developed for efficient chemo/photothermal therapy. The unique Au nanoframes@mSiO₂ spheres are elaborately prepared by utilizing Ag@mSiO₂ yolk–shell spheres as the template through spatially confined galvanic replacement method. Compared with the Ag@mSiO₂ yolk–shell spheres, the resultant Au nanoframes@mSiO₂ spheres show a strong and broad near‐infrared (NIR) absorbance in the 550–1100 nm region, high surface areas, and good biocompatibility. When irradiated with a NIR laser with a power intensity of 1 W cm^?2 at 808 nm, they can become highly localized heat sources through the photothermal effect. Moreover, the photothermal effect of the Au nanoframes can significantly promote the fast release of doxorubicin. The in vitro studies show obvious synergistic effects combining photothermal therapy and chemotherapy in the Au nanoframes@mSiO₂ spheres against Hela cells. It is believed that the as‐obtained multifunctional vehicles provide a promising platform for the combination of hyperthermia and chemotherapy for cancer treatment application.     

Influence of Morphological Homogeneity of Superspherical Gold Nanoparticles on Plasmonic Photothermal Heat Generation

The plasmonic photothermal (PPT) characteristics of gold nanostructures have been extensively investigated theoretically and experimentally due to their potential for use materials science and industry. The management of the size and shape of gold nanoparticles has been a key issue in the development of better solutions for PPT heat generation because their size and shape determine their resultant photothermal properties. However, the light absorption of gold nanostructures is mainly dependent on the wavelength and orientation of the incident light; hence, maintaining uniform size and shape is critical for achieving maximum photothermal energy. Morphologically homogeneous spherical gold nanoparticles, or super gold nanospheres prepared by slowly etching uniform octahedral gold nanoparticles, demonstrate better PPT heat generation compared with commercially available nonsmooth gold nanoparticles (GNSs). The PPT heating experiments show a maximum temperature difference of 5.7 °C between the super and ordinary GNSs with the same average maximum Feret's diameters, which result from the more efficient PPT heat power generation (20.6%) of the super GNSs. In an electromagnetic‐wave simulation, the super GNSs show lower polarization dependence and a 24.6% higher absorption cross‐section than ordinary GNSs.     

Facile Synthesis of Manganese Tellurite Nanoparticles for Magnetic Resonance Imaging-Guided Photothermal Therapy

In this study, manganese tellurite (MnTeO₃) nanoparticles are developed as theranostic agents for magnetic resonance imaging (MRI)-guided photothermal therapy of tumor. MnTeO₃ nanoparticles are synthesized via a simple one-step method. The as-synthesized MnTeO₃ nanoparticles with uniform size show good biocompatibility. In particular, MnTeO₃ nanoparticles exhibit a high photothermal conversion efficiency (η = 26.3%), which is higher than that of gold nanorods. Moreover, MnTeO₃ nanoparticles also have high MRI performance. The longitudinal relaxivity (r₁) value of MnTeO₃ nanoparticles is determined to be 8.08 ± 0.2 mm ⁻¹ s⁻¹, which is higher than that of clinically approved T₁-contrast agents Gd-DTPA (4.49 ± 0.1 mm ⁻¹ s⁻¹). The subsequent MnTeO₃ nanoparticles-mediated photothermal therapy displays a highly efficient ablation of tumor cells both in vitro and in vivo with negligible toxicity. It is demonstrated that MnTeO₃ nanoparticles can serve as promising theranostic agents with great potentials for MRI-guided photothermal therapy.     

Localized Surface Plasmon Resonance Enhanced Singlet Oxygen Generation and Light Absorption Based on Black Phosphorus@AuNPs Nanosheet for Tumor Photodynamic/Thermal Therapy

Although photodynamic therapy is an efficient therapeutic strategy for cancer treatment, it always suffers from the low singlet oxygen (¹O₂) yields owing to the weak absorption in optical transparent window of biological tissues. Herein, the black phosphorus (BP) nanosheet is integrated with gold nanoparticles (AuNPs) to simultaneously enhance the singlet oxygen generation and hyperthermia by localized surface plasmon resonance (LSPR) in cancer therapy. In the design, BP nanosheet employed as two‐dimension (2D) inorganic photosensitizer is hybridized with AuNPs through polyetherimide (PEI) as bridge to form BP‐PEI/AuNPs hybrid nanosheet. Such hybridation not only significantly increases the ¹O₂ production of BP nanosheet through maximizing the local field enhancement of AuNPs, but also significantly enhances the light absorption of BP nanosheet to promote photothermal effect by LSPR. Accordingly, about 3.9‐fold enhancement of ¹O₂ production and 1.7‐fold increasement of photothermal conversion efficiency are achieved compared with BP‐PEI alone upon single 670 nm laser irradiation. As a proof‐of‐concept model, BP‐PEI/AuNPs hybrid nanosheet with simultaneous dual‐modal phototherapy functions result in effective suppression of tumor growth with minimized side effects both in vitro and in vivo, indicating the great potential of the BP‐PEI/AuNPs hybrid nanosheet as an effective strategy to enhance the cancer therapy efficiency.     

Efficient and Rapid Synthesis of Radioactive Gold Nanoparticles by Dielectric Barrier Discharge

A compact bench‐top system based on a dielectric barrier plasma discharge (DBD), enables the rapid, automatable, and continuous‐flow synthesis of gold nanoparticles (AuNPs) and radioactive gold nanoparticles (¹⁹⁸AuNPs). AuNPs are used as radiosensitizers in oncology, and ¹⁹⁸AuNPs (half‐life: 2.7 d) have been suggested as potential cancer brachytherapy sources. Plasma applied at the surface of a liquid containing gold ions (AuCl₄^?) and dextran induces the production of AuNPs directly in water. This synthesis is monitored in real time by UV–visible spectrometry: the change of absorbance of the solution provides new insights on the growth dynamics of AuNPs by plasma synthesis. By balancing gold ions and surfactant molecules, particles with a diameter lying in the optimal range for radiosensitizing applications (28 ± 9 nm) are produced. The method yields a reduction of more than 99% of the gold ions within only 30 min of plasma treatment. A postsynthesis ripening of the AuNPs is revealed, monitored by UV–visible spectrometry, and quantified within the first few hours following plasma treatment. Radioactive ¹⁹⁸AuNPs are also produced by DBD synthesis and characterized by electron microscopy and single‐photon emission computed tomography imaging. The results confirm the efficiency of DBD reactors for AuNPs synthesis in oncology applications.     

Docetaxel‐Loaded Nanoparticles of Dendritic Amphiphilic Block Copolymer H40‐PLA‐b‐TPGS for Cancer Treatment

A dendritic amphiphilic block copolymer H40‐poly(d,l ‐lactide)‐block‐d‐α‐tocopheryl polyethylene glycol 1000 succinate (H40‐PLA‐b‐TPGS) is synthesized, which is then employed to develop a system of nanoparticles (NPs) loaded with docetaxel (DTX) as a model drug for cancer treatment due to its higher drug‐loading content and drug encapsulation efficiency, smaller particle size, faster drug release, and higher cellular uptake in comparison to the linear PLA polymer NPs and PLA‐b‐TPGS copolymer NPs. The drug‐loaded NPs are prepared by a modified nanoprecipitation method and characterized in terms of size and size distribution, surface morphology, drug release profile, and physical state of DTX. Cellular uptake of coumarin 6‐loaded NPs by MCF‐7 cancer cells is determined by flow cytometry and confocal laser scanning microscopy. The antitumor efficacy of the drug‐loaded NPs is investigated in vitro by MTT assay and in vivo by xenograft tumor model. The 72 h IC50 of the drug formulated in the PLA, PLA‐b‐TPGS, and H40‐PLA‐b‐TPGS NPs is found to be, 1.5 ± 0.3, 0.9 ± 0.1, and 0.15 ± 0.06 μg mL^?1, which are 7.3, 12.2, and 73.3‐fold effective than 11.0 ± 1.2 μg mL^?1 for Taxotere, respectively. Such advantages are further confirmed by the measurement of the tumor size and weight.     

Synergistic Effect of Photothermal Therapy and Chemotherapy Using Camptothecin‐Conjugated Gold Nanorods

A combinatorial treatment comprising thermal therapy and chemotherapy offers synergistic effects by inducing localized heat to targeted tumor sites and simultaneously delivering anticancer drugs to minimize systemic side effects and enhance the cytotoxic effect. In this study, a novel platform is developed for combining photothermal therapy and chemotherapy using drug‐conjugated gold nanorods (GNRs). Camptothecin (CPT), a model anticancer drug, is chemically conjugated onto GNRs through hydrolytic ester bonding. Upon near‐infrared (NIR) irradiation, localized heat from GNRs in target areas starts to destroy tissues and cells via photothermal therapy, and the elevated temperature accelerates hydrolysis of ester linkage, rapidly releasing drugs for chemotherapy. This combined NIR triggered thermal therapy and chemotherapy with CPT‐functionalized GNRs (CPT‐GNRs) presents a synergistic effect that has high efficacy in in vitro tests, thus providing a robust platform for efficient cancer treatments.     

A Curcumin-Based MOF Embedded Ag NPs and Modified with Polydopamine for Dual-Drug Delivery and Dual Biological Window Responsive Synergetic Cancer Therapy

A dual-drug delivery, pH-responsive composite nanoplatform (MAPD NPs) that can respond to two biological windows is developed to improve the efficacy of synergetic chemotherapic/photothermal/chemodynamic therapy (CDT) against tumors. This nanoplatform is surface-modified polydopamine (PDA) with excellent biocompatibility as the shell and Ag NPs as the catalyst for CDT. The curcumin (Cur) acts as an organic ligand to be encapsulated in metal−biomolecule frameworks (Bio-MOFs) by self-assembly, and Bio-MOF acts as a delivery carrier to deliver of DOX•HCl and then releases the Cur when it degrades in vivo. Moreover, Bio-MOF can be taken up by cells faster and accelerate cell death compared to free Cur. PDA modification enables MAP (PDA@MOF-Ag) to have photothermal properties under 808 and 1064 nm light irradiation, which not only improves the biocompatibility of MAP but also makes it produce high heat and abundant ·OH. The photothermal performance of MAP is stable after irradiation at 808 or 1064 nm, and the photothermal conversion efficiency reaches 63.57% and 26.25%. The survival rate of HeLa cells co-incubation with MAPD NPs after irradiation at 808 and 1064 nm decreases to 19.52 ± 0.69% and 30.48 ± 0.49%, respectively, providing a feasible scheme for the realization of deep tumor killing.     

Polyacrylamide Nanoparticles with Visible and Near‐Infrared Autofluorescence

Nowadays, self‐fluorescent materials such as quantum dots are widely studied and applied in biomedical field. However, the biggest obstacle is biocompatibility. Here, a novel autofluorescent nanoparticle is constructed by crosslinking polyacrylamide nanoparticles (PAANPs) that contain ε‐poly‐l ‐lysine with glutaraldehyde (named fPAANPs). The nanoparticle has a mean size of about 16 nm, a zeta potential of about +16 mV, and strong visible and near‐infrared autofluorescence. The nanoparticle can be efficiently internalized into cells with high biocompatibility, the LC50 of which in RAW264.7, HepG2, and Hepa1‐6 cells is 6, 9, and 7.5 mg mL^?1, respectively. The nanoparticle shows no visible impact on the mice vitality even at a high intravenously administered dose (126 mg kg^?1). The autofluorescence of fPAANPs shows high stability, persistence, allowing long‐term dynamic imaging for 25 d in subcutaneous injections and 18 d in xenograft tumors in mice. The nanoparticle thus provides a self‐traceable nanomaterial that can be exploited as drug carrier and potential photodynamic therapy photosensitizer.     

Multivalent Sorbitol Probes for Near-Infrared Photothermal Cancer Therapy

Photothermal therapy (PTT) is a targeted and non-invasive therapeutic strategy for effective cancer treatment. Image-guided PTT based on bifunctional near-infrared (NIR) fluorophores has received significant attention recently and the development of NIR fluorophores is advised for targeted imaging and precise cancer therapy. In this study, a multivalent sorbitol-conjugated NIR fluorophore (4Sorbitol-800) is used as a photothermal therapeutic agent for in vivo cancer imaging and therapy because of the high tumor-targetability of the sorbitol moieties and excellent photothermal properties of the NIR heptamethine cyanine core. This NIR fluorophore demonstrates an excellent photothermal effect, which increases the temperature of the tumor by 57.4 °C upon NIR laser irradiation (1.1 W cm⁻²) for 5 min. The volumes of HT-29 tumors targeted by 4Sorbitol-800 significantly decrease over 7 days after photothermal treatment. The 4Sorbitol-800 developed in this study exhibits good in vivo safety and a highly efficient antitumor capability. Therefore, 4Sorbitol-800 in combination with NIR laser irradiation has promising potential for future clinical applications with targeted photothermal cancer therapy.     

The transition from spark to arc discharge and its implications with respect to nanoparticle production

Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly(d,l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8–7.5 μmol/L), incubation time (1–2 h), and laser power (10–100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 ± 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm² and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 ± 3 % while for free InPc was 60 ± 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc.     

聚吡咯修饰的金纳米棒对肿瘤的光学相干层析成像的影响

聚吡咯(PPy)制备简单、生物相容性好,且在近红外(NIR)光谱范围内有很强的吸收,可作为一种良好的光热治疗试剂;同时,其NIR光吸收性质也可用于增强光学相干层析成像(OCT)的对比效果。因此,采用PPy对传统的OCT对比试剂——金纳米棒(GNR)进行表面修饰,有望获得对比效果更好且生物毒性较小的新型OCT对比试剂。选用吡咯为起始原料,在GNR表面进行一步简单的氧化聚合反应即可制备得到PPy修饰的金纳米棒(GNR-PPy)。利用紫外-可见吸收光谱,拉曼光谱和透射电子显微镜对制备的样品进行了分析和表征。构建小鼠荷瘤模型,以研究GNR-PPy对肿瘤OCT图像对比度的增强效果。采用中心波长为840 nm的OCT系统对注射了纳米粒子的肿瘤区域进行OCT成像。结果表明,肿瘤组织注射了GNR-PPy后,OCT信号衰减非常明显;与注射了GNR的OCT图像相比,840 nm光在GNR-PPy的OCT图像中的穿透深度明显更低。从OCT图像中抽提出一维的衰减曲线对OCT图像进行定量分析,发现注射有GNR-PPy肿瘤组织的OCT信号衰减系数明显高于注射了GNR的组织。表明,相对于GNR,GNR-PPy具有更好的OCT信号对比效果,这在增强肿瘤成像效果方面具有潜在应用价值。     

光辐照精确调控金纳米星枝杈长度及其光热性能探究

金纳米星是一种具有尖状结构的多分枝纳米颗粒.为了使金纳米星枝杈长度可控,利用HEPES作为体系的还原剂、稳定剂及形状诱导剂,在制备过程中进行光辐照,得到的金纳米星枝杈长度比无光辐照时的金纳米星枝杈长度短,而且不同波长光辐照得到的金纳米星枝杈长度有显著不同.在此基础上,分析了金纳米星枝杈长度变化的物理过程,提出光诱导金纳米星生长过程中枝杈长度变化的理论模型.测量了不同枝杈长度的金纳米星在光辐照下一定时间内的温度变化,计算了金纳米星的光热转换效率.实验结果表明,光辐照制备金纳米星能够精确控制金纳米星枝杈长度范围,从而调控金纳米星的光热转换效率.     

A Correlative Analysis of Gold Nanoparticles Internalized by A549 Cells

Fluorescently labeled nanoparticles are widely used to investigate nanoparticle cell interactions by fluorescence microscopy. Owing to limited lateral and axial resolution, nanostructures (<100 nm) cannot be resolved by conventional light micro­scopy techniques. Especially after uptake into cells, a common fate of the fluorescence label and the particle core cannot be taken for granted. In this study, a correlative approach is presented to image fluorescently labeled gold nanoparticles inside whole cells by correlative light and electron microscopy (CLEM). This approach allows for detection of the fluorescently labeled particle shell as well as for the gold core in one sample. In this setup, A549 cells are exposed to 8 nm Atto 647N‐labeled gold nanoparticles (3.3 × 10⁹ particles mL^?1, 0.02 μg Au mL^?1) for 5 h and are subsequently imaged by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Eight fluorescence signals located at different intracellular positions are further analyzed by TEM. Five of the eight fluorescence spots are correlated with isolated or agglomerated gold nanoparticles. Three fluorescence signals could not be related to the presence of gold, indicating a loss of the particle shell.