Comparison of the Synthesis and Heating Ability of Biofunctionalized Gold Nanoprisms and Nanorods for Bioapplications

Las nanopartículas de oro (AuNPs) son nanomateriales particularmente versátiles y útiles, lo cual queda reflejado en numerosas aplicaciones biomédicas. Previa excitación de su plasmón de resonancia de superficie localizado (LSPR), estas nanopartículas pueden llevar a cabo de forma eficiente transducciones luz-calor. La iluminación de las AuNPs por NIR se encuentra actualmente en fase de exploración para terapia fototérmica, imagen optoacústica y, recientemente, en sensores térmicos. Las bandas de LSPR de nanoprismas (AuNPrs) y nanorods (AuNRs) pueden ser ajustadas al rango NIR para que adquieran fuertes absorciones en la “ventana biológica”. Ante la excitación lumínica, la conversión fototérmica de la luz absorbida genera eficientes e intensos efectos de calentamiento local. Estas útiles partículas de oro anisotrópicas suelen denotar limitaciones como producciones en cantidades reducidas, subproductos indeseados y el uso de surfactantes tóxicos, además de arduas síntesis. Esta tesis ilustra sobre métodos de síntesis optimizados para obtener grandes cantidades de AuNPrs y AuNRs en medio acuoso donde la banda LSPR de ambos tipos de nanopartículas puede ajustarse a 800-1200 nm. Los coloides resultantes pueden ser conjugados con polietinenglicol heterobifuncional (PEG) para aumentar su estabilidad coloidal, 4-aminofenil β-D-glucopiranósido para aumentar la captación celular y el fluoróforo TAMRA para comprobar la presencia y localización de las AuNPs dentro de las células. La capacidad de calentamiento de las soluciones coloidales de AuNPrs tras la iluminación con un láser de clase IV a 1064 nm durante 5 minutos fue evaluada y comparada con los AuNRs. Como prueba de concepto, la biocompatibilidad y adecuación de estos AuNPrs como agentes fototérmicos fue estudiada en cultivos celulares. Debido a su fácil fabricación, funcionalización, y destacables características térmicas, estos AuNPrs parecen ser partículas más aptas que los AuNRs. Además, las AuNPrs representan un avance significativo en biocompatibilidad de nanopartículas y una atractiva alternativa a los agentes fototérmicos plasmónicos más utilizados

Gold nanoprism-nanorod face off: comparing the heating efficiency, cellular internalization and thermoablation capacity

[Aim]: This work compares the synthesis, heating capability, cellular internalization and thermoablation capacity of two different types of anisotropic gold nanoparticles: gold nanorods (NRs) and nanoprisms (NPrs). [Methods]: Both particles possess surface plasmon resonance absorption bands in the near-IR, and their heating efficiency upon irradiation with a continuous near-IR laser (1064 nm) was evaluated. The cellular internalization, location and toxicity of these PEG-stabilized NPrs and NRs were then assessed in the Vero cell line by transmission electron microscopy and inductively coupled plasma mass spectrometry analysis, and their ability to induce cell death upon laser irradiation was then evaluated and compared. [Results & conclusion]: Although both nanoparticles are highly efficient photothermal converters, NRs possessed a more efficient heating capability, yet the in vitro thermoablation studies clearly demonstrated that NPrs were more effective at inducing cell death through photothermal ablation due to their greater cellular internalization.This work was supported by Shanghai Jiao Tong University, Fondo Social de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public funding of Proyectos I+D+I – Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (project no. SAF2014–54763-C2–2-R) and the ERC-Starting grant 239931-NANOPUZZLE. For financial support SG Mitchell acknowledges the Fundación General CSIC (Programa ComFuturo); A Artiga acknowledges the Ministerio de Educación, Cultura y Deportes for an FPU grant (FPU014/06249); G Alfranca acknowledges the Ministry of Education for a China Scholarship Council (CSC) grant; and M Moros acknowledges the European Commission for an MCSA Fellowship (grant agreement no. 660228). TPeer Reviewe

Nanoparticles for multi-modality cancer diagnosis: simple protocol for self-assembly of gold nanoclusters mediated by gadolinium ions

It is essential to develop a simple synthetic strategy to improve the quality of multifunctional contrast agents for cancer diagnosis. Herein, we report a time-saving method for gadolinium (Gd3+) ions-mediated self-assembly of gold nanoclusters (GNCs) into monodisperse spherical nanoparticles (GNCNs) under mild conditions. The monodisperse, regular and colloidal stable GNCNs were formed via selectively inducing electrostatic interactions between negatively-charged carboxylic groups of gold nanoclusters and trivalent cations of gadolinium in aqueous solution. In this way, the Gd3+ ions were chelated into GNCNs without the use of molecular gadolinium chelates. With the co-existence of GNCs and Gd3+ ions, the formed GNCNs exhibit significant luminescence intensity enhancement for near-infrared fluorescence (NIRF) imaging, high X-ray attenuation for computed tomography (CT) imaging and reasonable r1 relaxivity for magnetic resonance (MR) imaging. The excellent biocompatibility of the GNCNs was proved both in vitro and in vivo. Meanwhile, the GNCNs also possess unique NIRF/CT/MR imaging ability in A549 tumor-bearing mice. In a nutshell, the simple and safe GNCNs hold great potential for tumor multi-modality clinical diagnosis

The true complexity of photothermal therapy: A brief perspective

Despite its undoubted potential, recent studies have began to highlight the complex processes of photothermal therapy. In this perspective, we tackle several issues that affect current research on photothermal therapy, such as the influence of other factors produced in the process, for instance reactive oxygen species or vapor nanobubbles. After focusing on several of the aspects of photothermal therapy that need further clarification, we step back and see this therapy from a wider angle in order to identify its weaknesses. Finally, we briefly summarize what we consider should be the orientation and key focus of future researches in order to establish the full potential of this rapidly advancing and promising therapy.This work was supported by Shanghai Jiao Tong University, the Scholarship Council (CSC) grants of the Ministry of Education People’s Republic of China; support also came from Fondo Social de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public funding of Proyectos I+D+I - Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (project n. SAF2014-54763-C2-2-R) and ERCPoC HOTFLOW (project 754609).Peer reviewe

Breath analysis based on surface-enhanced raman scattering sensors distinguishes early and advanced gastric cancer patients from healthy persons

Fourteen volatile organic compound (VOC) biomarkers in the breath have been identified to distinguish early gastric cancer (EGC) and advanced gastric cancer (AGC) patients from healthy persons by gas chromatography-mass spectrometry coupled with solid phase microextraction (SPME). Then, a breath analysis approach based on a surface-enhanced Raman scattering (SERS) sensor was developed to detect these biomarkers. Utilizing hydrazine vapor adsorbed in graphene oxide (GO) film, the clean SERS sensor is facilely prepared by in situ formation of gold nanoparticles (AuNPs) on reduced graphene oxide (RGO) without any organic stabilizer. In the SERS sensor, RGO can selectively adsorb and enrich the identified biomarkers from breath as an SPME fiber, and AuNPs well dispersed on RGO endow the SERS sensor with an effective detection of adsorbed biomarkers. Fourteen Raman bands associated with the biomarkers are selected as the fingerprints of biomarker patterns to distinguish persons in different states. The approach has successfully analyzed and distinguished different simulated breath samples and 200 breath samples of clinical patients with a sensitivity of higher than 83% and a specificity of more than 92%. In conclusion, the VOC biomarkers and breath analysis approach in this study can not only diagnose gastric cancer but also distinguish EGC and AGC. This work has great potential for clinical translation in primary screening diagnosis and stage determination of stomach cancer in the near future.This work is supported by the National Key Basic Research Program (973 Project) (No. 2015CB931802, No. 2010CB933901), National Natural Scientific Fund (Nos. 81225010, 81327002, and 31100717), 863 Project of China (2014AA020700), and Shanghai Science and Technology Fund (Nos. 13NM1401500 and 15DZ2252000).Peer Reviewe

A plasmonic thermal sensing based portable device for lateral flow assay detection and quantification

Point-of-care testing (POCT) is widely used for early diagnosis and monitoring of diseases. Lateral flow assay (LFA) is a successfully commercial tool for POCT. However, LFA often suffers from a lack of quantification and analytical sensitivity. To solve these drawbacks, we have previously developed a thermal LFA using plasmonic gold nanoparticles for thermal contrast into a portable device. Although this methodology significantly improves the analytical sensitivity compared with conventional visual detection, quantification problems are still remaining. In this study, we optimized the operating conditions for the device using conduction and radiation thermal sensing modes allowing the quantification of LFA. The limit of detection of the strips merely containing nanoparticles was decreased by 5-fold (conduction mode) and 12-fold (radiation mode) compared to traditional visual detection. The effect of the ambient temperature was studied for both methods of detection showing that the radiation mode was more affected by the ambient temperature than the conduction mode. To validate the thermal sensing method, human chorionic gonadotropin (HCG) biomarker was quantified using our LFA strips, obtaining a detection limit of 2.8 mIU/mL when using the radiation method of detection.This work was supported by the National Foundational Basic Research Project of China (2017YFA0205301 and 2015CB931802), National Nature Scientific Foundation (81803094, 81602184, 81822024, and 81571729), Shanghai Municipal Commission of Economy and Information Technology Fund (No. XC-ZXSJ-02-2016-05), and the medical engineering cross project of Shanghai Jiao Tong University (YG2016ZD10 and YG2017ZD05), the Project of Thousand Youth Talents from China, and the National Key Research, Development Program of China (2017YFC1200904), PROSCANEXO-Transcan2 project and DGA and Fondos Feder (Bionanosurf E15_17R).Peer reviewe

GSH-triggered sequential catalysis for tumor imaging and eradication based on star-like Au/Pt enzyme carrier system

Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment. In this regard, we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic. The multifunctional probes consisted of a gold/platinum star-shaped core (Au/Pt star) conjugated with a GSH-sensitive disulfide bond (S–S), a targeting ligand (rHSA-FA), a near-infrared fluorophore (IR780) and glucose oxidase (GOx). When systemically administered in a xenografted murine model, the probes specifically targeted the tumor sites. As the disulfide linker was cleaved by intracellular GSH, the IR780 molecules could be released for photo-thermal therapy & photodynamic therapy (PTT&PDT) and imaging. Subsequently, the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system: GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity, and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic ·OH for tumor oxidative damage. Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release, real-time imaging ability, and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features, which provides a potential strategy for effective tumor theragnostic.We thank the support of the National Basic Research Program of China (Nos. 2017YFA0205301 and 2015CB931802), the National Natural Scientific Foundation of China (Nos. 81903169, 81803094, 81602184, 81822024, and 81571729), Shanghai Municipal Commission of Economy and Information Technology Fund (No. XC-ZXSJ-02-2016-05), the Medical Engineering Cross Project of Shanghai Jiao Tong university (Nos. YG2016ZD10 and YG2017Z D05), the Project of Thousand Youth Talents from China, and the National Key Research and Development Program of China (No. 2017YFC1200904). We also are grateful for the financial support of Shanghai Sailing Program (No. 19YF1422300), Sponsor from Startup Fund for Yongman Research at SJTU (No. 18X100040044) and Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument (No. 15DZ2252000) are also acknowledged.Peer reviewe

Point-of-care fluidic immunosensor chip based on near infrared-absorbing nanoparticles for cancer biomarker detection

Trabajo presentado a la Conference on Advanced Materials and Devices for Nanomed (AMA4MED), celebrada en Valencia (España) del 3 al 4 de mayo de 2022.Peer reviewe

Gold nanoprism-nanorod face off: in vitro comparison of the heating efficiency, celular internalisation and thermoablation capacity of gold nanorods and nanoprisms

Resumen del trabajo presentado al 6th EuCheMS Chemistry Congress, celebrado en Sevilla (España) del 11 al 15 de septiembre de 2016.Upon excitation of their surface plasmon resonance (SPR) band, plasmonic gold nanoparticles (AuNPs) undergo efficient light-to-heat transduction. Near-Infrared (NIR) illumination of AuNPs is currently being applied to a range of biomedical applications: in photothermal therapy (PTT) optoacoustic imaging (OI) and as thermal biosensors. The SPR bands of both triangular gold nanoprisms (AuNPrs) and gold nanorods (AuNRs) can be fine-tuned in the NIR range to exhibit strong absorption in the so-called ‘biological window’, where photothermal conversion of the absorbed light energy generates an efficient and sharp local heating effect. Typically, anisotropic AuNPs exhibit an inherent limitation to their downstream application due to time-consuming syntheses and poor synthetic yields, along with unwanted by-products and the use of cytotoxic surfactants. Our group recently reported a high-yielding synthesis of biocompatible single-crystal AuNPrs whereby the LSPR band can be fine-tuned from 800-1100 nm5. Here we discuss how these particles can be used to induce apoptosis (programmed cell death) in vitro and how their heating efficiency and ability to induce cell death compares with gold nanorods (AuNRs) of the same SPR band wavelength.Peer Reviewe

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Urinary exosomes containing specific biomarkers have recently been considered as novel potential non-invasive candidates for renal disease diagnosis. However, the development of urinary exosomes in basic research and their subsequent diagnostic application are impeded by the lack of an efficient isolation method. One of the main challenges during urinary exosomes isolation is how to remove a large number of Tamm Horsfall proteins (around 92 kDa) and other biological components from exosome enrichment mixture. Herein, we report a facile and low-cost isolation method for highlypurified human urinary exosomes based on dialysis. The key protocol for exosome isolation includes only two steps: (1) Healthy person urines were collected. 10 mL urine in 300 kDa dialysis tubes was firstly dialyzed in phosphate-buffered saline solution three times for sequential nine hours; (2) The dialysis suspension was concentrated to 200 μL by using 100 kDa ultracentrifuge tubes to achieve urinary exosome isolation. For verification, the concentrated solution was examined by western blot, transmission electronic microscopy, atomic force microscopy and qNano, which demonstrated the highly-purified urinary exosomes were present. Furthermore, a total of 359 proteins were identified by the proteomic analysis of purified urinary exosomes from healthy persons. Those results demonstrated that highly-purified urinary exosomes could be achieved by our isolation method; 359 proteins were identified from healthy persons. Further works will focus on screening and identifying disease-related biomarkers from human urine exosomes for clinical diagnosis