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Breast cancer is a complex and diverse disease that requires accurate diagnostic methods and customized treatment approaches to enhance patient outcomes. In this study, we investigate the potential of nylon-11 nanoparticles (nylon NPs) for both imaging and therapy of breast cancer. Nylon NPs possess excellent photoacoustic properties, which enable them to detect and locate drug delivery to the tumor with high sensitivity. This suggests that nylon NPs may be a valuable tool for improving breast cancer diagnosis and treatment. Comprehensive characterization has been performed, including morphological analysis and spectroscopic studies. Further modification with diagnostic and therapeutic agents, such as trastuzumab, sorafenib, and nutlin-3a, enhances their specificity and efficacy in targeting breast cancer cells. The drug-loaded nanoparticles exhibit controlled release profiles under various pH conditions, mimicking the tumor microenvironment. Cytocompatibility studies reveal the biocompatibility of bare nylon NPs, while drug-loaded nanoparticles show concentration-dependent cytotoxic effects, indicating their potential as therapeutic agents. Moreover, cellular internalization studies confirm the efficient uptake by breast cancer cells. Overall, this research lays the groundwork for the development of novel nanomedicine approaches aimed at addressing the challenges associated with breast cancer diagnosis and treatment, offering promising avenues for precise cancer management.

Abstract Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract

Cosmic rays entering the Earth's atmosphere produce showers of secondary particles such as protons, neutrons, and muons. The interaction of these particles with oxygen-16 (16O) in minerals such as ice and quartz can produce carbon-14 (14C). In glacial ice, 14C is also incorporated through trapping of 14C-containing atmospheric gases (14CO2, 14CO, and 14CH4). Understanding the production rates of in situ cosmogenic 14C is important to deconvolve the in situ cosmogenic and atmospheric 14C signals in ice, both of which contain valuable paleoenvironmental information. Unfortunately, the in situ 14C production rates by muons (which are the dominant production mechanism at depths of >6 m solid ice equivalent) are uncertain. In this study, we use measurements of in situ 14C in ancient ice (>50 ka) from the Taylor Glacier, an ablation site in Antarctica, in combination with a 2D ice flow model to better constrain the compound-specific rates of 14C production by muons and the partitioning of in situ 14C between CO2, CO, and CH4. Our measurements show that 33.7 % (±11.4 %; 95 % confidence interval) of the produced cosmogenic 14C forms 14CO and 66.1 % (±11.5 %; 95 % confidence interval) of the produced cosmogenic 14C forms 14CO2. 14CH4 represents a very small fraction (%) of the total. Assuming that the majority of in situ muogenic 14C in ice forms 14CO2, 14CO, and 14CH4, we also calculated muogenic 14C production rates that are lower by factors of 5.7 (3.6–13.9; 95 % confidence interval) and 3.7 (2.0–11.9; 95 % confidence interval) for negative muon capture and fast muon interactions, respectively, when compared to values determined in quartz from laboratory studies (Heisinger et al., 2002a, b) and in a natural setting (Lupker et al., 2015). This apparent discrepancy in muogenic 14C production rates in ice and quartz currently lacks a good explanation and requires further investigation.

Erica Locatelli,1,* Yan Li,2,* Ilaria Monaco,1 Wei Guo,3 Mirko Maturi,1 Luca Menichetti,4 Paolo Armanetti,4 Robert C Martin,2 Mauro Comes Franchini1 1Department of Industrial Chemistry “Toso Montanari”, Bologna, Italy; 2Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, USA; 3Department of Hematology, The First Hospital of Jilin University, Changchun, China; 4Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy *These authors contributed equally to this work Introduction and purpose: Cancer stem cells (CSCs) present a higher capacity to evade being killed by cancer agents and developing chemoresistance, thus leading to failure of conventional anticancer therapeutics. Nanomaterials specifically designed for targeting and treating not only tumor cells, but also CSCs, may encompass therapeutic and diagnostic tools, thus successfully eradicating the tumor. Materials and methods: Polymeric micelles simultaneously loaded with gold nanorods (GNRs) and Adriamycin were prepared and used as a novel therapeutic and diagnostic weapon. Epithelial cell adhesion molecule (EpCAM) is an important CSC surface marker and has been exploited in this work as an active targeting agent. Photoacoustic imaging was applied for GNR individuation and tissue recognition. Results: The nanosystem was demonstrated to be able to elicit effective targeting of cancer cells and cause their killing, in particular under laser ablation. Moreover, ex vivo photoacoustic imaging is able to clearly identify tumor regions thanks to GNR’s contrast. Conclusion: The nanosystem can be considered a powerful and promising theranostic weapon for hepatocellular carcinoma treatment. Keywords: gold nanorods, drug delivery, photoacoustic imaging, photothermal therapy, EpCAM, cancer stem cells

Abstract Near infrared (NIR)‐resonant gold nanoparticles (AuNPs) hold great promise in cancer diagnostics and treatment. However, translating the theranostic potential of AuNPs into clinical applications still remains a challenge due to the difficulty to improve the efficiency and specificity of tumor delivery in vivo as well as the clearance from liver and spleen to avoid off target toxicity. In this study, endothelial colony forming cells (ECFCs) are exploited as vehicles to deliver AuNPs to tumors. It is first demonstrated that ECFCs display a great capability to intake AuNPs without losing viability, and exert antitumor activity per se. Using a human melanoma xenograft mouse model, it is next demonstrated that AuNP‐loaded ECFCs retain their capacity to migrate to tumor sites in vivo 1 day after injection and stay in the tumor mass for more than 1 week. In addition, it is demonstrated that ECFC‐loaded AuNPs are efficiently cleared by the liver over time and do not elicit any sign of damage to healthy tissue.

Bioconjugation of a recently developed photoacoustic nanoprobe, based on silica-templated eumelanin-silver hybrid nanoparticles (MelaSil_Ag-NPs), with human serum albumin (HSA) is disclosed herein as an efficient and practical strategy to improve photostability and to perform SPARC mediated internalization in breast cancer cells. Modification of NPs with HSA induced a slight viability decrease in breast cancer cells (HS578T) and normal breast cells (MCF10a) when incubated with HSA-NPs up to 100 μg/mL concentration for 72 h and a complete suppression of hemotoxicity for long incubation times. Uptake experiments with MelaSil_Ag-HSA NPs indicated very high and selective internalization via SPARC in HS578T (SPARC positive cells) but not in MCF10a (SPARC negative cells), as evaluated by using endocytosis inhibitors. The binding of SPARC to HSA was confirmed by Co-IP and Dot-blot assays. Additional studies were performed to analyze the interaction of MelaSil_Ag-HSA NPs with protein corona. Data showed a dramatic diminution of interacting proteins in HSA conjugated NPs compared to bare NPs. HSA-coated MelaSil_Ag-NPs are thus disclosed as a novel functional nanohybrid for potential photoacoustic imaging applications.

Gold nanorods (GNRs) showed to be a suitable contrast agent in photoacoustics (PA), and are able to provide a tunable absorption contrast against background tissue, while a detectable PA signal can be generated from highly localized and targeted areas. A crucial issue for these imaging techniques is represented by the discrimination between exogenous and endogenous contrast and the assessment of the real PA signal magnitude. The application of image resolution/unmixing methods was implemented and optimized to recover the relative magnitude spectra and distribution maps of image constituents of the biological sample based on multivariate analysis (multivariate curve resolution—alternating least squares, MCR-ALS) in the presence of GNRs with tunable absorption properties. The proposed data analysis methodology is demonstrated on real PA images from experimental animal models and ex-vivo preparations.

Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed.

Ultrasound (US) imaging is a well-established diagnostic technique to image soft tissues in real time, while photoacoustic (PA) is an emerging imaging technique employed to collect molecular information. Integration of PA and US imaging provides complementary information enhancing diagnostic accuracy without employing ionizing radiations. The development of contrast agents able to combine PA and US features is pivotal to improve the significance of PAUS imaging and for PAUS-guided treatment of neoplasms. Here, we demonstrate in relevant ex-vivo models that disassembling passion fruit-like nano-architectures ( pf NAs) can be employed in PAUS imaging. pf NAs are composed by silica nanocapsules comprising aggregates of commercial NIR-dyes-modified polymers and ultrasmall gold nanoparticles. The intrinsic US and PA features of pf NAs have been fully characterized and validated in tissue-mimicking materials and in ex vivo preparations. Moreover, the application of a multi-parametric approach has allowed the increase of information extrapolated from collected images for a fine texture analysis. [ABSTRACT FROM AUTHOR]

Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5β1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5β1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study., Competing Interests: Competing interests statement:F.C., A.C., M.A., I.L., E.A., M. Maturi, E.L., and M.C.F. are inventors of patents regarding GNRs functionalized with peptide Iso4.

The development of biosafe theranostic nanoplatforms has attracted great attention due to their multifunctional behavior, reduced potential toxicity, and improved long-term safety. When considering photoacoustic contrast agents and photothermal conversion tools, melanin and constructs like melanin are highly appealing due to their ability to absorb optical energy and convert it into heat. Following a sustainable approach, in this study, silver-melanin like-silica nanoplatforms are synthesized exploiting different bio-available and inexpensive phenolic acids as potential melanogenic precursors and exploring their role in tuning the final systems architecture. The UV-Vis combined with X-Ray Diffraction investigation proves metallic silver formation, while Transmission Electron Microscopy analysis reveals that different morphologies can be obtained by properly selecting the phenolic precursors. By looking at the characterization results, a tentative formation mechanism is proposed to explain how phenolic precursors' redox behavior may affect the nanoplatforms' structure. The antibacterial activity experiments showed that all synthesized systems have a strong inhibitory effect on Escherichia coli, even at low concentrations. Furthermore, very sensitive Photoacoustic Imaging capabilities and significant photothermal behavior under laser irradiation are exhibited. Finally, a marked influence of phenol nature on the final system architecture is revealed resulting in a significant effect on both biological and photoacoustic features of the obtained systems. These melanin-based hybrid systems exhibit excellent potential as triggerable nanoplatforms for various biomedical applications., (© 2024 Wiley‐VCH GmbH.)

Bioinspired nanoparticles have recently been gaining attention as promising multifunctional nanoplatforms for therapeutic applications in cancer, including breast cancer. Here, the efficiency of the chemo-photothermal and photoacoustic properties of hybrid albumin-modified nanoparticles (HSA-NPs) loaded with doxorubicin was evaluated in a three-dimensional breast cancer cell model. The HSA-NPs showed a higher uptake and deeper penetration into breast cancer spheroids than healthy breast cell 3D cultures. Confocal microscopy revealed that, in tumour spheroids incubated with doxorubicin-loaded NPs for 16 h, doxorubicin was mainly localised in the cytoplasm, while a strong signal was detectable at the nuclear level after 24 h, suggesting a time-dependent uptake. To evaluate the cytotoxicity of doxorubicin-loaded NPs, tumour spheroids were treated for up to 96 h with increasing concentrations of NPs, showing marked toxicity only at the highest concentration of doxorubicin. When doxorubicin administration was combined with laser photothermal irradiation, enhanced cytotoxicity was observed at lower concentrations and incubation times. Finally, the photoacoustic properties of doxorubicin-loaded NPs were evaluated in tumour spheroids, showing a detectable signal increasing with NP concentration. Overall, our data show that the combined effect of chemo-photothermal therapy results in a shorter exposure time to doxorubicin and a lower drug dose. Furthermore, owing to the photoacoustic properties of the NPs, this nanoplatform may represent a good candidate for theranostic applications.

Background and Objectives: Gold nanorod-assisted photothermal therapy (GNR-PTT) is a cancer treatment whereby GNRs incorporated into the tumour act as photo-absorbers to elevate the thermal destruction effect. In the case of bladder, there are few possible routes to target the tumour with GNRs, namely peri/intra-tumoural injection and intravesical instillation of GNRs. These two approaches lead to different GNR distribution inside the tumour and can affect the treatment outcome., Methodology: The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation., Results: Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues., Conclusions: Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Gold nanorods assisted photothermal therapy (GNR-PTT) is a new cancer treatment technique that has shown promising potential for bladder cancer treatment. The position of the bladder cancer at different locations along the bladder wall lining can potentially affect the treatment efficacy since laser is irradiated externally from the skin surface. The present study investigates the efficacy of GNR-PTT in the treatment of bladder cancer in mice for tumours growing at three different locations on the bladder, i.e., Case 1: closest to skin surface, Case 2: at the bottom half of the bladder, and Case 3: at the side of the bladder. Investigations were carried out numerically using an experimentally validated framework for optical-thermal simulations. An in-silico approach was adopted due to the flexibility in placing the tumour at a desired location along the bladder lining. Results indicate that for the treatment parameters considered (laser power 0.3 W, GNR volume fraction 0.01% v/v), only Case 1 can be used for an effective GNR-PTT. No damage to the tumour was observed in Cases 2 and 3. Analysis of the thermo-physiological responses showed that the effectiveness of GNR-PTT in treating bladder cancer depends not only on the depth of the tumour from the skin surface, but also on the type of tissue that the laser must pass through before reaching the tumour. In addition, the results are reliant on GNRs with a diameter of 10 nm and an aspect ratio of 3.8 - tuned to exhibit peak absorption for the chosen laser wavelength. Results from the present study can be used to highlight the potential for using GNR-PTT for treatment of human bladder cancer. It appears that Cases 2 and 3 suggest that GNR-PTT, where the laser passes through the skin to reach the bladder, may be unfeasible in humans. While this study shows the feasibility of using GNRs for photothermal ablation of bladder cancer, it also identifies the current limitations needed to be overcome for an effective clinical application in the bladder cancer patients., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hybrid nanomaterials have attracted research interest owing to their intriguing properties, which may offer new diagnostic options with triggering features, able to realize a new kind of tunable nanotherapeutics. Hybrid silica/melanin nanoparticles (NPs) containing silver seeds (Me-laSil_Ag-HSA NPs) disclosed relevant photoacoustic contrast for molecular imaging. In this study we explored therapeutic function in the same nanoplatform. For this purpose, MelaSil_Ag-HSA were loaded with doxorubicin (DOX) (MelaSil_Ag-HSA@DOX) and tested to assess the efficiency of drug delivery combined with concurrent photothermal treatment. The excellent photothermal properties allowed enhanced cytotoxic activity at significantly lower doses than neat chemotherapeutic treatment. The results revealed that MelaSil_Ag-HSA@DOX is a promising platform for an integrated photothermal (PT) chemotherapy approach, reducing the efficacy concentration of the DOX and, thus, potentially limiting the several adverse side effects of the drug in in vivo treatments.

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

Gold nanorods (GNRs) showed to be a suitable contrast agent in photoacoustics (PA), and are able to provide a tunable absorption contrast against background tissue, while a detectable PA signal can be generated from highly localized and targeted areas. A crucial issue for these imaging techniques is represented by the discrimination between exogenous and endogenous contrast and the assessment of the real PA signal magnitude. The application of image resolution/unmixing methods was implemented and optimized to recover the relative magnitude spectra and distribution maps of image constituents of the biological sample based on multivariate analysis (multivariate curve resolution-alternating least squares, MCR-ALS) in the presence of GNRs with tunable absorption properties. The proposed data analysis methodology is demonstrated on real PA images from experimental animal models and ex-vivo preparations.

Near infrared (NIR)-resonant gold nanoparticles (AuNPs) hold great promise in cancer diagnostics and treatment. However, translating the theranostic potential of AuNPs into clinical applications still remains a challenge due to the difficulty to improve the efficiency and specificity of tumor delivery in vivo as well as the clearance from liver and spleen to avoid off target toxicity. In this study, endothelial colony forming cells (ECFCs) are exploited as vehicles to deliver AuNPs to tumors. It is first demonstrated that ECFCs display a great capability to intake AuNPs without losing viability, and exert antitumor activity per se. Using a human melanoma xenograft mouse model, it is next demonstrated that AuNP-loaded ECFCs retain their capacity to migrate to tumor sites in vivo 1 day after injection and stay in the tumor mass for more than 1 week. In addition, it is demonstrated that ECFC-loaded AuNPs are efficiently cleared by the liver over time and do not elicit any sign of damage to healthy tissue., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed.

Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were investigated as part of a human phospho-kinase array analysis, and CSF-1 and VEGFR-2 protein levels were measured by ELISA. The intracellular concentration of lenvatinib in ATC cells was measured by combined reversed-phase liquid chromatography-tandem mass spectrometry. An ATC subcutaneous xenograft tumor model in nude mice was treated with vinorelbine, lenvatinib, or vinorelbine plus lenvatinib. After treatment with vinorelbine, lenvatinib, a significant antiproliferative effect in ATC cell lines was observed. The concomitant treatment of vinorelbine and lenvatinib revealed synergism for all the fractions of affected cells. A decrease in ABCB1 expression was reported in both ATC cell lines treated with the lenvatinib plus vinorelbine combination, as was an increase in the intracellular concentration of lenvatinib. The combination caused a decrease in Akt, GSK3α/β, PRAS40 and Src phosphorylation, and in both CSF-1 mRNA and protein levels. In the subcutaneous tumor model, the combination reduced the tumor volume during the treatment period. Our results establish the synergistic ATC antitumor activity of a vinorelbine and lenvatinib combination., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bioconjugation of a recently developed photoacoustic nanoprobe, based on silica-templated eumelanin-silver hybrid nanoparticles (MelaSil_Ag-NPs), with human serum albumin (HSA) is disclosed herein as an efficient and practical strategy to improve photostability and to perform SPARC mediated internalization in breast cancer cells. Modification of NPs with HSA induced a slight viability decrease in breast cancer cells (HS578T) and normal breast cells (MCF10a) when incubated with HSA-NPs up to 100 μg/mL concentration for 72 h and a complete suppression of hemotoxicity for long incubation times. Uptake experiments with MelaSil_Ag-HSA NPs indicated very high and selective internalization via SPARC in HS578T (SPARC positive cells) but not in MCF10a (SPARC negative cells), as evaluated by using endocytosis inhibitors. The binding of SPARC to HSA was confirmed by Co-IP and Dot-blot assays. Additional studies were performed to analyze the interaction of MelaSil_Ag-HSA NPs with protein corona. Data showed a dramatic diminution of interacting proteins in HSA conjugated NPs compared to bare NPs. HSA-coated MelaSil_Ag-NPs are thus disclosed as a novel functional nanohybrid for potential photoacoustic imaging applications., (Copyright © 2020 Sanità, Armanetti, Silvestri, Carrese, Calì, Pota, Pezzella, d’Ischia, Luciani, Menichetti and Lamberti.)

Developing safe and high efficiency contrast tools is an urgent need to allow in vivo applications of photoacoustics (PA), an emerging biomolecular imaging methodology, with poor invasiveness, deep penetration, high spatial resolution and excellent endogenous contrast. Eumelanins hold huge promise as biocompatible, endogenous photoacoustic contrast agents. However, their huge potential is still unexplored due to the difficulty to achieve at the same time poor aggregation in physiologic environment and high PA contrast. This study addresses both issues through the design of a biocompatible photoacoustic nanoprobe, named MelaSil_Ag-NPs, relying on silica-templated eumelanin formation as well as eumelanins redox and metal chelating properties to reduce Ag + ions and control the growth of generated metal nanoparticles. This strategy allowed self-structuring of the system into a core-shell architecture, where the Ag core was found to boost PA signal, despite the poor eumelanin content. Obtained hybrid nanoplatforms, showed stable photoacoustic properties even under long irradiation. Furthermore, conjugation with rhodamine isothiocyanate allowed particles detection through fluorescent imaging proving their multifunctional potentialities. In addition, they were stable towards aggregation and efficiently endocytosed by human pancreatic cancer cells (BxPC3 and Panc-1) displaying no significant cytotoxicity. Such numerous features prove huge potential of those nanoparticles as a multifunctional platform for biomedical applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ultrasound (US) imaging is a well-established diagnostic technique to image soft tissues in real time, while photoacoustic (PA) is an emerging imaging technique employed to collect molecular information. Integration of PA and US imaging provides complementary information enhancing diagnostic accuracy without employing ionizing radiations. The development of contrast agents able to combine PA and US features is pivotal to improve the significance of PAUS imaging and for PAUS-guided treatment of neoplasms. Here, we demonstrate in relevant ex-vivo models that disassembling passion fruit-like nano-architectures (pfNAs) can be employed in PAUS imaging. pfNAs are composed by silica nanocapsules comprising aggregates of commercial NIR-dyes-modified polymers and ultrasmall gold nanoparticles. The intrinsic US and PA features of pfNAs have been fully characterized and validated in tissue-mimicking materials and in ex vivo preparations. Moreover, the application of a multi-parametric approach has allowed the increase of information extrapolated from collected images for a fine texture analysis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recently, a number of photoacoustic (PA) agents with increased tissue penetration and fine spatial resolution have been developed for molecular imaging and mapping of pathophysiological features at the molecular level. Here, we present bio-conjugated near-infrared light-absorbing magnetic nanoparticles as a new agent for PA imaging. These nanoparticles exhibit suitable absorption in the near-infrared region, with good photoacoustic signal generation efficiency and high photo-stability. Furthermore, these encapsulated iron oxide nanoparticles exhibit strong super-paramagnetic behavior and nuclear relaxivities that make them useful as magnetic resonance imaging (MRI) contrast media as well. Their simple bio-conjugation strategy, optical and chemical stability, and straightforward manipulation could enable the development of a PA probe with magnetic and spectroscopic properties suitable for in vitro and in vivo real-time imaging of relevant biological targets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herein we report the synthesis of a resilient nanosystem based on silica-coated magnetic MnFe 2 O 3 nanoparticles conjugated to fluorescein and PEGylated gold nanorods embedded in polymeric micelles (MnFe 2 O 4 @SiO 2 @GNRs@PMs), for magnetic-photoacoustic-optical triple-modality imaging. The magnetic relaxivity of the nanosystem has been evaluated, revealing high r 2 /r 1 ratios that suggest the effectiveness of the nanosystem as the T 2 -contrast agent. In addition, contrast-based fluorescence imaging has been tested both in vitro and ex vivo, showing that the nanosystem exhibits the suitable optical properties of fluorescein, with contrast intensities comparable with previously reported results. Finally, photoacoustic, due to gold nanorods, performances of the nanosystem have been evaluated, revealing good linearity between concentration and photoacoustic response in the 25-250 nM concentration under irradiation at 690 nm. The results showed a contrast-to-noise ratio (CNR) as high as 60 in a mouse leg subcutaneously injected with the nanosystem. Biocompatibility studies revealed no hemolytic effect induced by the nanoconstruct, revealing the applicability of the studied diagnostic tool for medical studies.

Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-tonoiseratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.