Hollow Gold Nanospheres Research Articles

Efficient Photothermal Sensor Based on Coral-Like Hollow Gold Nanospheres for the Sensitive Detection of Sulfonamides.

Gold nanoparticles (AuNPs), universally regarded as colorimetric signal reporters, are widely employed in lateral flow immunoassays (LFIAs). However, it is difficult for AuNPs-LFIA to achieve a wide range and sensitive detection. Herein, novel coral-like hollow gold nanospheres (CHGNPs) are synthesized. The growth of gold nanospheres can be regulated to obtain a multibranched and hollow construction. The obtained CHGNPs possess intense broadband absorption across the visible to near-infrared region, exhibiting a high molar extinction coefficient of 14.65×1011 M-1 cm-1 and a photothermal conversion efficiency of 79.75%. Thus, the photothermal/colorimetric dual-readout LFIA is developed based on CHGNPs (CHGNPs-PT-LFIA and CHGNPs-CM-LFIA) to effectively improve the detection sensitivity and broaden the detection range in regard to sulfonamides (SAs). The limits of detection of the CHGNPs-PT-LFIA and CHGNPs-CM-LFIA reached 1.9 and 2.8pgmL-1 for the quantitative detection of sulfaquinoxaline, respectively, which are 6.3-fold and 4.3-fold lower than that of the AuNPs-LFIA. Meanwhile, the CHGNPs-PT-LFIA broadened the detection range to three orders of magnitude, which ranged from 2.5 to 5000 pg mL-1. The synthesized photothermal CHGNPs have been proven effective in improving the performance of the LFIA and provide a potential option for the construction of sensing platforms.

Synthesis, Characterization and Biosafety Evaluation of Hollow Gold Nanospheres.

In order to assess the biosafety of HAuNS using zebrafish models and the cancer cell lines HepG2, HEK293, and A549, this study prepared HAuNS in a variety of sizes and alterations. By oxidizing cobalt nanoparticles encased in gold shells, HAuNS were created. In the meantime, PEG- and PEI-coated HAuNS were created. The diameters of the HAuNS that were produced were 30~40 nm, 50~60 nm, and 70~80 nm. MTT assay was used to assess the toxicity of HAuNS on HepG2, HEK293, and A549 cells. For the investigation of their toxicities, HAuNS (50~60 nm) of various concentrations were incubated with zebrafish embryos. Then, cell death was determined using acridine orange staining. In a cell line model, it was demonstrated that purified HAuNS exhibit lower toxicity than unpurified HAuNS. Meanwhile, it was discovered that surface-modified HAuNS was less hazardous than unmodified HAuNS. Unpurified HAuNS (50.60 nm) exposure to embryos caused deformity and increased mortality. Moreover, embryos exposed to HAuNS displayed an increase in cell death, showing that HAuNS can put zebrafish under physiological stress. The possible toxicity of HAuNS is now more understood thanks to this investigation. The details could improve our comprehension of the nanotoxicity of medication delivery systems. Comparing HAuNS (50~60 nm) to the other two particle sizes, its toxicity was quite low. Compared to unpurified HAuNS, purified HAuNS displayed less toxicity. Comparing PEI-HAuNS and HAuNS to PEG-HAuNS, cytotoxicity was found to be lower. Our data support the use of pure HAuNS, HAuNS-PEG, and HAuNS (50~60 nm) as possible photothermal conductors when seen as a whole.

A novel gold-polymer-antibody conjugate for targeted (radio-photothermal) treatment of HepG2 cells

Localization of the near-infrared (NIR) plasmonic nanoparticles at the tumor sites is essential for safe and efficient photothermal therapy of cancer. In this work, two biocompatible polymers: modified poly(ethylene glycol) (PEG) and branched polyethyleneimine (bPEI) were used to bind plasmonic hollow gold nanospheres (HAuNS) to the tumor-specific antibody, atezolizumab (ATZ). The photo-immunoconjugate (HAuNS-PEI-PEG-ATZ) was prepared via a simple and cost-effective procedure. The conjugate was also prepared with the radioiodinated antibody (ATZ-131I) to combine the targeted radio- and photothermal cytotoxic actions against human hepatoma (HepG2) cells. In vitro study revealed that attachment to the antibody and the use of cellular internalizing polymers enhanced the cellular localization of both gold and the radiotherapeutic Iodine-131. Compared to bare gold nanoparticles, (HAuNS-PEI-PEG-ATZ) conjugate exhibited a significantly enhanced photothermal ablation of HepG2 cells after laser irradiation (0.4 W cm−2, 5 min). Laser irradiation of the cells treated with the radiolabeled conjugate (HAuNS-PEI-PEG-ATZ-131I) exhibited the highest cytotoxicity against HepG2 cells due to the combinatorial cytotoxic effects.

Intra-arterial delivery of doxorubicin-loaded hollow gold nanospheres—photothermal ablation and chemoembolisation therapy in a rabbit VX2 liver cancer model

Hepatocellular carcinoma (HCC) is associated with a high mortality rate. In this study, we aimed to investigate the therapeutic effect and safety of hepatic arterial administration of doxorubicin (Dox)-loaded hollow gold nanospheres (Dox@HAuNSs) combined with photothermal ablation (PTA) in a rabbit VX2 liver cancer model established by implanting VX2 tumour cells into rabbit livers. Rabbits were randomly divided into four treatment groups: physiological saline solution (control); lipiodol and doxorubicin (Dox + Lp); lipiodol and Dox@HAuNS (Dox@PEG-HAuNS + Lp); and lipiodol, Dox@PEG-HAuNS, and photothermal ablation (Dox@PEG-HAuNS + Lp + PTA). Dox release from Dox@PEG-HAuNS in the tumour was detected using fluorescence microscopy. Tumour size and liver-kidney function were assessed in each rabbit preoperatively and on postoperative days 3, 7, and 14. Necrosis, proliferation, and micro-vessel density of VX2 tumours were estimated in peripheral tumour tissues. Dox release from Dox@PEG-HAuNS was increased with a subsequent increase in tumour necrosis in liver tumours after PTA, whereas the tumour volume and proliferation decreased. However, the aspartate aminotransferase and alanine aminotransferase levels indicated transient liver damage. Thus, intra-arterial delivery of Dox@PEG-HAuNS combined with PTA can suppress VX2 liver cancer growth. Dox@PEG-HAuNS + Lp + PTA is also associated with transient liver damage in rabbits. The combination of Dox@PEG-HAuNS chemoembolisation and PTA could be a potential therapeutic approach for HCC and it has broad application prospects.

Enhanced refractive index sensitivity of localized surface plasmon resonance inflection points in single hollow gold nanospheres with inner cavity

Hollow gold nanoparticles have great potential for localized surface plasmon resonance (LSPR) sensing. In this study, we investigated the refractive index (RI) sensitivities of single hollow gold nanosphere (HAuNS) with thin Au shell and inner cavity and single solid gold nanosphere (AuNS) in media with different RIs. The HAuNS exhibited a remarkable improvement in the RI sensitivity than the AuNS of similar size. The increased RI sensitivity of HAuNSs was ascribed to plasmon coupling between the inner and outer surface of the Au nanoshell. We then investigated the homogeneous LSPR scattering inflection points (IFs) to better understand the RI sensitivity of single HAuNS. The LSPR IF at the long wavelength side exhibited a better RI sensitivity compared to the wavelength shift of its counterpart LSPR maximum peak. Furthermore, the single HAuNS showed a remarkable improvement in the RI sensitivity at the LSPR IFs when compared to the AuNS of similar size. Therefore, we provided a new insight into the effect of inner cavity of HAuNS on the RI sensitivity of homogeneous LSPR IFs for use in LSPR-based biosensors.

Near-Infrared Light Absorbing Silver-Coated Hollow Gold Nanostars for Surface-Enhanced Raman Scattering Detection of Bovine Serum Albumin Using Capping Ligand Exchange

Two novel urchinlike plasmonic nanostructures, hollow gold nanostars (HNSs) and silver-coated hollow gold nanostars (AgHNSs), were synthesized using hollow gold nanospheres (HGNs) as templates. The particle morphology was assessed by transmission electron microscopy (TEM), optical properties were characterized by UV–vis spectroscopy, and elemental composition was evaluated by both inductively coupled plasma-optical emission spectrometry (ICP-OES) and energy-dispersive X-ray (EDX) analysis. Both the HNSs and AgHNSs exhibit tunable structural and optical properties. Their unique star-shaped structure provides the desired “hot spots” for enhancing the electromagnetic (EM) field for surface-enhanced Raman scattering (SERS) applications, while their near-infrared (NIR) absorption is ideal for biomedical applications. A comparative analysis of the relative SERS enhancement using rhodamine 6G (R6G) showed that HNSs reported herein have an order of magnitude higher relative enhancement over previously reported HNSs. Moreover, AgHNSs have a 4-fold increase in the SERS signal compared to HNSs. Discrete dipole approximation (DDA) simulations of electric field enhancement were used to corroborate the experimental findings. The comparison between the experimental and theoretical results suggests that the significant increase in SERS enhancement cannot be completely explained by the larger dielectric constant of silver. The branching of individual spikes, or the increased binding efficacy of the analyte to the nanoparticles, likely also plays an important role. To further explore the applicability of these novel structures, successful capping ligand exchange from citrate to pentanethiol was used to switch the surface charge from negative to positive to facilitate the SERS detection of dried bovine serum albumin (BSA). AgHNSs are stable and effective NIR-absorbing substrates for SERS detection of biological samples. Elemental analyses of AgHNSs, in conjunction with DDA simulations, provide insights into their enhancement mechanism.

Hollow Gold Nanosphere Templated Synthesis of PEGylated Hollow Gold Nanostars and Use for SERS Detection of Amyloid Beta in Solution.

Hollow gold nanospheres (HGNs) have been used as the template for seed-mediated growth of multibranched hollow gold nanostars (HNS). The HGNs were synthesized via anerobic reduction of cobalt chloride to cobalt nanoparticles and then formation of a gold shell via galvanic replacement followed by the oxidation of the cobalt core. We obtained control of the inner core size of the HGNs by increasing the size of the sacrificial cobalt core and by varying the ratio of B(OH)3/BH4 using boric acid rather than 48 h aged borohydride. We synthesized the HNS by reducing Au3+ ions in the presence of Ag+ ions using ascorbic acid, creating a spiky morphology that varied with the Au3+/Ag+ ratio. A broadly tunable localized surface plasmon resonance was achieved through control of both the inner core and the spike length. Amyloid beta (Aβ) was conjugated to the HNS by using a heterobifunctional PEG linker and identified by the vibrational modes associated with the conjugated ring phenylalanine side chain. A bicinchoninic acid assay was used to determine the concentration of Aβ conjugated to HNS as 20 nM, which is below the level of Aβ that negatively affects long-term potentiation. Both the core size and spike length were shown to affect the optical properties of the resulting nanostructures. This HGN templated method introduced a new parameter for enhancing the plasmonic properties of gold nanostars, namely, the addition of a hollow core. Hollow gold nanostars are highly desirable for a wide range of applications, including high sensitivity disease detection and monitoring.

Spatiotemporal Temperature and Pressure in Thermoplasmonic Gold Nanosphere-Water Systems.

We offer a detailed investigation of the photophysical properties of plasmonic solid and hollow gold nanospheres suspended in water by combining ultrafast transient absorption (TA) spectroscopy with molecular dynamics (MD) simulations. TA reveals that hollow gold nanospheres (HGNs) exhibit faster excited state relaxation and larger amplitude acoustic phonon modes than solid gold nanoparticles of the same outer diameter. MD simulation carried out on full scale nanoparticle-water models (over 10 million atoms) to simulate the temporal evolution (0-100 ps) of the thermally excited particles (1000 or 1250 K) provides atomic-scale resolution of the spatiotemporal temperature and pressure maps, as well as visualization of the lattice vibrational modes. For the 1000 K HGN, temperatures upward of 500 K in the vicinity of the shell surface were observed, along with pressures up to several hundred MPa in the inner cavity, revealing potential use as a photoinduced nanoreactor. Our approach of combining TA and MD provides a path to better understanding how thermal-structural properties (such as expansion and contraction) and thermal-optical properties (such as modulated dielectrics) manifest themselves as TA signatures. The detailed picture of heat transfer at interfaces should help guide nanoparticle design for a wide range of applications that rely on photothermal conversion, including photothermal coupling agents for nanoparticle-mediated photothermal therapy and photocatalysts for light-driven chemical reactions.

Enhanced immune memory through a constant photothermal-metabolism regulation for cancer prevention and treatment

Tumor vaccine inducing effective and perdurable antitumor immunity has a great potential for cancer prevention and therapy. The key indicator for a successful tumor vaccine is boosting the immune system to produce more memory T cells. Although many tumor vaccines have been designed, few of them involve in actively regulating immune memory CD8+T cells. Here a tumor vaccine vector (TA-Met@MS) by encapsulating tumor antigen (TA), metformin (Met) and Hollow gold nanospheres (HAuNS) into poly (lactic-co-glycolic acid) (PLGA) microspheres was presented. TA via the treatment of photothermal therapy (PTT) showed high immunogenicity and immune-adjuvant effectiveness. And NIR light-mediated photothermal effect can lead to a pulsed-release behavior of TA and Met from the microspheres. The released TA can regulate primary T cell expansion and contraction, and stimulate the production of effector T cells at the early immunization stage. The metabolic behavior of the cells is then intervened from glycolysis into fatty acids oxidation (FAO) through the activation of AMPK mediated by Met, which can enhance T cell survival and facilitate the differentiation of memory CD8+T cells. This study may present a valuable insight to design tumor vaccine for enhanced cancer prevention and therapy.

Photothermal sterilization cellulose patch with hollow gold nanoparticles

In this work, we prepared hollow gold nanospheres (HAuNS) with rough surfaces and strong light absorption in the NIR region. Based on as-made HAuNS materials, photothermal sterilization patches using filter paper was prepared. When 808 nm and 4 W/cm2 laser light was irradiated on the patch containing 50 ppm of HAuNS, the temperature of patch surface increased to 63 °C. The photothermal conversion efficiency of the patch was found to be 38.8% and is enhanced by the overlap between the heat emission of nearby particles in the patch. The prepared patch was placed into an Escherichia coli culture medium with irradiation of NIR (pulsed laser by manually on/off). E. coli in direct contact with patch could be killed by local heating on the patch surface. Approximately 99% of the bacteria was killed compared to control test. Therefore, this patch can be applied to wounds to block the entry of bacteria from the outside for the prevention of secondary infections and the acceleration of treatment with the photothermal effect caused by NIR irradiation.

Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy

BackgroundDoxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Adult New Zealand white rabbits (N = 25) were inoculated with VX2 tumors into the left lobe of the liver. The animals were then randomized to sham surgery (N = 5), PTA only (N = 3), Dox@HAuNS only (N = 5), HAuNS + PTA (N = 5), and Dox@HAuNS + PTA (N = 7). Nanoparticles were delivered as an emulsion with Lipiodol (Guerbet, France) via a trans-arterial approach. Following nanoparticle delivery, PTA was performed using an 808-nm fibered laser at 1.5 W for 3 min. Thermography during PTA demonstrated a sustained elevation in tumoral temperature in both HAuNS + laser and Dox@HAuNS + laser treatment groups relative to animals that underwent laser treatment without prior nanoparticle delivery.ResultsThere was a significant decrease in tumor volumes in all three treatment arms relative to control arms (P = 0.004). Concentrations of intratumoral doxorubicin were significantly greater in animals treated with laser compared to those that were not treated with laser (P < 0.01).ConclusionsDoxorubicin-loaded HAuNS is a promising therapeutic agent for dual ablation/chemoembolization treatment of liver cancer.

Oxygen self-enriched nanoplatform combined with US imaging and chemo/photothermal therapy for breast cancer

Oxygen-saturated perfluorohexane-cored, cisplatin (Pt)-decorated hollow gold nanospheres (Pt-HAuNS-PFH@O2) have been synthesized for ultrasound (US) imaging-guided tumor treatment depending on chemo/photothermal therapy, relief of hypoxia, and photothermal induced US contrast signal. Both NIR laser-induced hyperthermia generation by gold nanospheres and acidity triggered release of Pt resulted in high toxicity after internalization by breast cancer cells. According to ex vivo immunofluorescence investigation and in vivo pharmacodynamic studies on MDA-MB-231 tumor bearing mice, the susceptibility of tumors to Pt-HAuNS-PFH@O2 was improved by the relief of hypoxia. In addition, US imaging under different conditions verified the amplified US contrast property of Pt-HAuNS-PFH@O2 by the heat-dependent liquid–gas conversion of PFH. Overall, Pt-HAuNS-PFH@O2 can be promisingly used as an oxygen self-enriched nanoplatform for US imaging-guided chemo/photothermal therapy.

CD271 antibody-functionalized HGNs for targeted photothermal therapy of osteosarcoma stem cells

Cancer stem cells (CSCs) are considered to maintain the vitality of tumor cell populations through self-renewal and infinite proliferation, but their accessibility is still under investigation. In addition, CSCs are more resistant to chemotherapy and radiotherapy compared with common tumor cells. This study aimed to develop a kind of novel and feasible nanomaterial for targeted photothermal ablation of osteosarcoma stem cells, which could be a promising anticancer strategy. The osteosarcoma stem cells were extracted by serum-free culture and we further verified the stem cell properties. We evaluated the expression of CD271 by flow cytometry. PEGylated multifunctional hollow gold nanospheres (HGNs) were prepared based on CD271 monoclonal antibody. Bifunctional SH-PEG-COOH was used to facilitate the covalent linkage between HGNs and antibody. The efficient uptake and distribution of the functionalized HGNs were investigated using ICP-MS and TEM. Morphological studies and quantitative apoptosis evaluation were performed to detect the effect of photothermal therapy (PTT). Afterwards, we explored the possible mechanism by which PTT induced targeted killing of cancer stem cells. Osteosarcoma cells isolated from serum-free culture were detected to show stem cell properties. CD271 was found to be a potential novel surface marker for osteosarcoma stem cells. By conjugating with CD271 monoclonal antibody, these biomimetic nanoparticles can be targeted and absorbed by osteosarcoma stem cells. HGNs-PEG-CD271 achieved excellent cell viability inhibition compared with non-targeted PEGylated HGNs upon near-infrared (NIR) laser irradiation. The mechanism of targeted killing may be related to the apoptosis pathway and DNA double-strand injuries. CD271 was considered to be a surface biomarker for osteosarcoma stem cells. Functionalized HGNs based on CD271 antibody exhibited excellent potential for targeted PTT, which may be a promising strategy for osteosarcoma treatment.

A novel fluorescence biosensor for the detection and imaging of tumor-related mRNA in living cells based on Au//hGNPs-FA nanocarrier

Au//hGNPs-FA nanocarriers-based novel fluorescence strategy for the detection and imaging of tumor-related mRNA in the living cells is described. Au//hGNPs-FA is a new nanocarrier with large capacity, high release efficiency and specificity. In Au//hGNPs-FA, ssDNA-bound gold nanoparticles (AuNPs-T1) could tightly combine with ssDNA-bound hollow gold nanospheres (hGNPs-T2) by hybridization of T1 and T2. Since AuNPs of diameter 16 nm could block the hGNPs’ pores of diameter 8.4 nm, the non-specific release of signal substances can be significantly reduced. New matching scheme of AuNPs and hGNPs not only utilized the powerful load capacity of hGNPs, but also realized efficient sealing and specific release. The results of extracellular experiments showed that the method can detect mRNA standards in the range of 1 pM to 20 nM, and the minimum detection limit is 850 fM. More importantly, combined with FA, the efficiency of Au//hGNPs-FA entering cells was increased by 20%. And, the fluorescence strategy could detect mRNA in living cells with high specificity and sensitivity, even in single cell with very low content. Therefore, the new strategy has the potential to monitor the expression of mRNA in tumor cells accurately.

Trifluoroacetic Acid as a Theranostic Ablation Agent.

HomeRadiology: Imaging CancerVol. 2, No. 1 Previous Research HighlightsFree AccessTrifluoroacetic Acid as a Theranostic Ablation AgentGary D. LukerGary D. LukerGary D. LukerPublished Online:Jan 31 2020https://doi.org/10.1148/rycan.2020204005MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To test efficacy of trifluoroacetic acid (TFA) for chemical ablation of liver tumors and optimize a fluorine 19 (19F) MRI sequence to detect TFA in tissue.■ Key Result: Real-time 19F MRI successfully detected TFA in porcine liver tissue, and histologic findings effectively verified coagulation and disruption of liver architecture.■ Impact: This study established an integrated imaging and therapy protocol to apply TFA as a theranostic agent for chemical ablation of solid tissue.Ablation methods encompass a wide range of minimally invasive techniques to destroy liver tumors, particularly smaller tumors in patients for whom surgery is not safe or feasible. Incomplete ablation remains a clinical challenge with residual tumor leading to local recurrence and potentially more aggressive disease. Although ablations most commonly use radiofrequency, laser, or other thermal methods, high-flow blood vessels can produce a local heat-sink effect that reduces peak temperatures of ablation and elimination of nearby tumors. Chemical ablations do not suffer from limitations of a local heat-sink, but agents used for chemical ablation may flow irregularly in tissue with associated off-target injury and systemic toxicities. To develop a theranostic agent for chemical ablation of liver tumors, the authors combined trifluoroacetic acid (TFA) as an ablation agent with fluorine 19 (19F) MRI. 19F MRI provides quantitative images with very minimal background signal, although low sensitivity typically requires millimolar concentrations of 19F to produce diagnostic quality images. Chemical ablation uses much higher concentrations, potentially overcoming sensitivity limits of 19F MRI. The investigators optimized a 19F MRI sequence to detect TFA in phantoms with signal-to-noise correlating directly with concentration. 19F MRI detected distribution and relative amounts of TFA used to ablate porcine liver tissue ex vivo, and histologic findings showed extensive damage to hepatocytes at concentrations of 0.5 mol/L TFA or higher. By developing a 19F MRI method to detect TFA in liver tissue, this research provides a new approach to optimize chemical ablation strategies and potentially a novel theranostic technique for future clinical translation.Highlighted ArticleEinstein SA, Thompson EA, Guo C, Whitley EM, Bankson JA, Cressman ENK. Application of trifluoroacetic acid as a theranostic agent for chemical ablation of solid tissue. J Vasc Interv Radiol 2020;31(1):169–175. doi: https://doi.org/10.1016/j.jvir.2019.05.002Highlighted ArticleEinstein SA, Thompson EA, Guo C, Whitley EM, Bankson JA, Cressman ENK. Application of trifluoroacetic acid as a theranostic agent for chemical ablation of solid tissue. J Vasc Interv Radiol 2020;31(1):169–175. doi: https://doi.org/10.1016/j.jvir.2019.05.002 Crossref, Medline, Google ScholarArticle HistoryPublished online: Jan 31 2020 FiguresReferencesRelatedDetailsRecommended Articles Colorectal Cancer Liver Metastases: Biopsy of the Ablation Zone and Margins Can Be Used to Predict Oncologic OutcomeRadiology2016Volume: 280Issue: 3pp. 949-959Combined Angio-CT Systems: A Roadmap Tool for Precision Therapy in Interventional OncologyRadiology: Imaging Cancer2021Volume: 3Issue: 5Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation—Chemoembolization Therapy in RatsRadiology2016Volume: 281Issue: 2pp. 427-435Effects of Microwave Ablation on Arterial and Venous Vasculature after Treatment of Hepatocellular CarcinomaRadiology2016Volume: 281Issue: 2pp. 617-624Midterm Safety and Efficacy of Irreversible Electroporation of Malignant Liver Tumors Located Close to Major Portal or Hepatic VeinsRadiology2017Volume: 285Issue: 3pp. 1023-1031See More RSNA Education Exhibits Maximizing Procedural Success! A Trainee's Guide to Imaging Equipment in the IR SuiteDigital Posters2018The Emerging Role of Contrast-Enhanced Ultrasound in Oncological InterventionDigital Posters2018A Practical Guide of Locoregional Treatment for Patients with Hepatocellular CarcinomaDigital Posters2019 RSNA Case Collection Spindle cell lipomaRSNA Case Collection2022Extralobar Pulmonary Sequestration RSNA Case Collection2021Hepatic AdenomatosisRSNA Case Collection2021 Vol. 2, No. 1 Metrics Altmetric Score PDF download

Efficient gram-scale continuous production of near-infrared-sensitive liposomes for light-triggered delivery of polyinosinic-polycytidylic acid

Liposomes can be used as drug carriers, biocompatible with human cells. However, efficient on-demand release of the liposome payload still remains a challenge. Also, sophisticated liposome formulations, such as those encapsulating one or more drugs together with a suitable compound to facilitate triggered release, are usually prepared in complex multistep batch procedures with low (e.g. milligram) production rates. The aim of this work is to develop a continuous supercritical CO2 based scalable process for the production of near-infrared (NIR) light-sensitive liposomes. Hollow Gold Nanospheres (HGN), about 5 nm large, have been synthesized as light sensitive agents for triggered release and, then, they were embedded in controlled size liposomes (from 0.75 ± 0.19 μm to 1.76 ± 0.71 μm) together with biological active compounds Polyinosinic-polycytidylic Acid (PIC) and Bovine Serum Albumin (BSA), using a supercritical assisted process. High encapsulation efficiency of all components, up to 95%, with a gram-scale production of 1 g/h of HGN loaded liposomes have been obtained. Drug release tests verified that NIR light could be efficiently used as a stimulus on these vectors to achieve drug release on-demand. Produced liposomes presented high biocompatibility.

Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an ‘eat me’ signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.

Smart MMP2-Responsive Nanoprobe for Activatable Fluorescence Imaging-Guided Local Triple-Combination Therapies with Single Light.

Elaborately designed stimuli-responsive smart systems simultaneously enabling activatable imaging and selective treatment are highly desirable for precise diagnosis and therapy of cancer. Herein, such a smart theranostic nanoprobe composed of hollow gold nanospheres (HAuNs), photosensitizer (PS), matrix metalloproteinase 2 (MMP2) substrate peptide, and model drug doxorubicin (DOX) was designed. In the design, HAuNs served as the acceptor of Förster resonance energy transfer (FRET), photothermal therapy (PTT) reagent, and nanocarrier. The fluorescence and 1O2 generation of PS were inhibited by HAuNs through FRET effect, avoiding phototoxicity to normal tissues during circulation. Meanwhile, owing to the MMP2-triggered peptide cleavage, the PS could be efficiently activated in a tumor for selective fluorescence imaging and photodynamic therapy (PDT). The recovered fluorescence could be applied for detecting MMP2, locating tumor in vivo, and further guiding the local triple-combination therapies including PDT, PTT, and chemotherapy. The synergistic treatments of activated PDT, PTT, and controlled DOX release were achieved with single light, which provided the best therapeutic effects with enhanced stability and remarkably reduced nonspecific toxicity of PS and anticancer drug. This study helps to design novel stimuli-responsive systems for precise molecular sensing and site-specific cancer treatment.

Near-infrared light-responsive, pramipexole-loaded biodegradable PLGA microspheres for therapeutic use in Parkinson's disease

Parkinson’s disease (PD) is associated with symptoms such as tremor and bradykinesia which, together with a rigorous dosing regimen, can place an untenable burden on patients. These issues underscore the need for triggerable, modulated drug delivery systems. Currently, pramipexole (PRX) is the most widely used non-ergot dopamine agonist for the treatment of PD. In this study, near-infrared light-responsive PRX and hollow gold nanospheres (HGNS)-loaded biodegradable poly (D, L-lactide-co-glycolide) (PLGA) microspheres (PRX/HGNS MS) were fabricated using solid-in-oil-in-water (S/O/W) and water-in-oil-in-water (W/O/W) emulsion-solvent evaporation techniques to achieve modulated drug release. The PRX/HGNS MS were uniform, with an average diameter of approximately 24 µm, favorable PRX and HGNS encapsulation efficiencies (51.71 ± 0.54% and 65.15 ± 2.30%, respectively) and rapid, controllable drug release both in vitro and in vivo. Cytotoxicity tests revealed no significant differences between HGNS and PRX/HGNS MS when compared with a negative control. Pharmacodynamics and immunohistochemistry studies revealed a more rapid recovery of striatum in the group treated with PRX/HGNS MS produced using the S/O/W method. The results clearly demonstrate that light-responsive PRX/HGNS MS produced using the S/O/W method have the potential to address PD patients’ mobility problems in a smart, controllable and remotely triggerable manner.

Preparation of novel cisplatin-conjugated hollow gold nanospheres for targeting cervical cancer.

Cervical cancer is a deadly gynecological malignancy in need of innovative treatment strategies. Emerging preclinical data has suggested the benefits of nanocarriers over the traditional chemotherapy for cancer treatment. In particular, gold nanoparticles are gaining popularity due to gold's inert nature, limited side effects, good cytocompatibility, and flexibility in preparation/modification. We conjugated polyethylene glycol (PEG) with hollow gold nanospheres (HGNs) and loaded the pegylated HGNs with an anticancer drug, cisplatin to target cervical cancer. HGNs were irradiated with noninfrared laser to increase the penetration of drug into tumor tissue and improve the delivery of cisplatin. We investigated the comparative characterization studies of prepared cisplatin loaded pegylated HGNs (cis PEG-HGNs), free cisplatin, cisplatin loaded HGNs (cis-HGNs), cis PEG-HGNs without laser, and cis PEG-HGNs with laser and its effects over cervical cancer cells. Transmission electron microscopy photomicrographs confirmed the integrity of prepared HGNs. While no significant difference was observed between encapsulation efficiency and drug loading of cis-HGNs (84.6%) and cis PEG-HGNs (86.7%), the encapsulation efficiency increased almost twice in HGNs, compared with control gold nanoparticles (GNs) because of the hollow cavity in HGNs. In-vitro cytotoxicity was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using HeLa cells. With irradiation, HGNs induced much elevated cytotoxicity. Not only HGNs were internalized by HeLa cells, they were retained in the cellular compartment. We also tested formulations in vivo and observed that the irradiated cis-HGNs and cis PEG-HGNs were most effective in regressing tumors in mice.