Browsing by Subject "porous silicon"

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  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Helder A.; Airaksinen, Anu J.; Makila, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Hélder A.; Airaksinen, Anu J.; Mäkilä, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Fontana, Flavia; Albertini, Silvia; Correia, Alexandra; Kemell, Marianna Leena; Lindgren, Rici; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni Tapio; Ferrari, Franca; Almeida Santos, Helder (2018)
    Biohybrid nanosystems are at the center of personalized medicine, affording prolonged circulation time and targeting to the disease site, and serving as antigenic sources of vaccines. The optimization and functionality parameters of these nanosystems vary depending on the properties of the core particles. In this work, the effects of the core particles’ surface charge and hydrophobicity are evaluated on the nanosystem coating with vesicles derived from plasma membrane. The measured parameters are the dimensions, surface charge, shape, and stability of the biohybrid nanosystems, both in buffer and in biologically relevant media (plasma and simulated synovial fluid). Moreover, the cytocompatibility properties of the developed nanosystems are evaluated in different cell lines mimicking the target cell populations and other districts of the body involved in the distribution and elimination of the nanoparticles. Finally, the immunological profile of the particles is investigated, highlighting the absence of immune activation promoted by the nanoplatforms.
  • Fontana, Flavia; Fusciello, Manlio; Groeneveldt, Christianne; Capasso, Cristian; Chiaro, Jacopo; Feola, Sara; Liu, Zehua; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Cerullo, Vincenzo; Santos, Hélder A. (2019)
    Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.
  • Qi, Shengcai; Zhang, Pengfei; Ma, Ming; Yao, Minghua; Wu, Jinjin; Mäkilä, Ermei; Salonen, Jarno; Ruskoaho, Heikki; Xu, Yuanzhi; Santos, Helder A.; Zhang, Hongbo (2019)
    Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.
  • Liu, Dongfei; Lipponen, Katriina; Quan, Peng; Wan, Xiaocao; Zhan, Hongbo; Makilä, Ermei; Salonen, Jarno; Kostiainen, Risto; Hirvonen, Jouni; Kotiaho, Tapio; Santos, Helder A. (2018)
    By exploiting its porous structure and high loading capacity, porous silicon (PSi) is a promising biomaterial to fabricate protocells and biomimetic reactors. Here, we have evaluated the impact of physicochemical properties of PSi particles [thermally oxidized PSi, TOPSi; annealed TOPSi, AnnTOPSi; (3-aminopropyl) triethoxysilane functionalized thermally carbonized PSi, APTES-TCPSi; and thermally hydrocarbonized PSi, THCPSi] on their surface interactions with different phospholipids. All of the four phospholipids were similarly adsorbed by the surface of PSi particles, except for TOPSi. Among four PSi particles, TOPSi with hydrophilic surface and smaller pore size showed the weakest adsorption toward phosphatidylcholines. By increasing the pore size from roughly 12.5 to 18.0 nm (TOPSi vs AnnTOPSi), the quantity of phosphatidylcholines adsorbed by TOPSi was enhanced to the same level of hydrophilic APTES-TCPSi and hydrophobic THCPSi. The 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) exhibited the highest release ratio of phospholipids from all four PSi particles, and phosphatidylserine (DPPS) showed the lowest release ratio of phospholipids from PSi particles, except for TOPSi, which adsorbed less phospholipids due to the small pore size. There is consistency in the release extent of phospholipids from PSi particles and the isosteric heat of adsorption. Overall, our study demonstrates the importance of pore size and surface chemistry of PSi particles as well as the structure of phospholipids on their interactions. The obtained information can be employed to guide the selection of PSi particles and phospholipids to fabricate highly ordered structures, for example, protocells, or biomimetic reactors.
  • Liu, Zehua; Li, Yunzhan; Li, Wei; Xiao, Chen; Liu, Dongfei; Dong, Chao; Zhang, Ming; Mäkilä, Ermei; Kemell, Marianna; Salonen, Jarno; Hirvonen, Jouni T.; Zhang, Hongbo; Zhou, Dawang; Deng, Xianming; Santos, Helder A. (2018)
    Herein, a novel nanohybrid based on porous silicon, gold nanoparticles (Au NPs), and acetalated dextran (DPSi/DAu@AcDEX) is reported to encapsulate and deliver one drug and increase the computer tomography (CT) signal for acute-liver-failure (ALF) theranostics. A microfluidic-assisted method is used to co-encapsulate different NPs in a single step. By alternating the surface properties of different NPs and by modulating the composition of the organic phase, both PSi and Au NPs are effectively encapsulated into the polymer matrix simultaneously, thus further achieving a multifunctional application. This system can be used to identify pathologically changes in the tissues and selectively deliver drugs to these sites. The loading of a therapeutic compound (XMU-MP-1) improves the drug solubility, precise, in situ drug delivery, and the drug-functioning time. In vivo results confirm a superior treatment effect and better compliance of this newly developed nanoformulation than free compound. This nanosystem plays a crucial role in targeting the lesion area, thus increasing the local drug concentration important for ALF reverse-effect. Moreover, the residence of Au NPs within the matrix further endows our system for CT-imaging. Altogether, these results support that this nanohybrid is a potential theranostic platform for ALF.
  • Şen, Karaman Didem; P., Sarparanta Mirkka; M., Rosenholm Jessica; J., Airaksinen Anu (2018)
    Abstract Recent progress in the development of silica? and silicon?based multimodality imaging nanoprobes has advanced their use in image?guided drug delivery, and the development of novel systems for nanotheranostic and diagnostic applications. As biocompatible and flexibly tunable materials, silica and silicon provide excellent platforms with high clinical potential in nanotheranostic and diagnostic probes with well?defined morphology and surface chemistry, yielding multifunctional properties. In vivo imaging is of great value in the exploration of methods for improving site?specific nanotherapeutic delivery by silica? and silicon?based drug?delivery systems. Multimodality approaches are essential for understanding the biological interactions of nanotherapeutics in the physiological environment in vivo. The aim here is to describe recent advances in the development of in vivo imaging tools based on nanostructured silica and silicon, and their applications in single and multimodality imaging.
  • Cheng, Ruoyu; Wang, Shiqi; Moslova, Karina; Mäkilä, Ermei; Salonen, Jarno; Li, Jiachen; Hirvonen, Jouni; Xia, Bing; Santos, Hélder A. (2022)
    Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle’s behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard 1H NMR experiments. We optimized the hydrolysis conditions to degrade the PSi, providing mobility to the molecules for NMR detection. The NMR parameters were also optimized by relaxation delay and the number of scans to provide reliable NMR spectra. With an internal standard, we quantitatively analyzed the surficial amine groups and their sequential modification of polyethylene glycol. Our investigation provides a reliable, fast, and straightforward method in quantitative analysis of the surficial modification characterization of PSi requiring a small amount of sample.
  • Lumen, Dave; Näkki, Simo; Imlimthan, Surachet; Lambidis, Elisavet; Sarparanta, Mirkka; Xu, Wujun; Lehto, Vesa-Pekka; Airaksinen, Anu J. (2019)
    Polyethylene glycol (PEG) has been successfully used for improving circulation time of several nanomaterials but prolonging the circulation of porous silicon nanoparticles (PSi NPs) has remained challenging. Here, we report a site specific radiolabeling of dual-PEGylated thermally oxidized porous silicon (DPEG-TOPSi) NPs and investigation of influence of the PEGylation on blood circulation time of TOPSi NPs. Trans-cyclooctene conjugated DPEG-TOPSi NPs were radiolabeled through a click reaction with [In-111]In-DOTA-PEG(4)-tetrazine (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and the particle behavior was evaluated in vivo in Balb/c mice bearing 4T1 murine breast cancer allografts. The dual-PEGylation significantly prolonged circulation of [In-111]In-DPEG-TOPSi particles when compared to non-PEGylated control particles, yielding 10.8 +/- 1.7% of the injected activity/g in blood at 15 min for [In-111]In-DPEG-TOPSi NPs. The improved circulation time will be beneficial for the accumulation of targeted DPEG-TOPSi to tumors.
  • Espo, Erika (Helsingin yliopisto, 2021)
    Nowadays, targetability studies usually require sample modifications and quite often, examination requires the use of directed light in harmful wavelengths. The surface plasmon resonance (SPR) technique does not need either of those actions. With SPR technology, the targetability of biomolecules can be studied in real-time and without any additional labels. The SPR response is received by measuring the change in surface plasmon resonance conditions due to refractive index changes caused by material interactions in the vicinity of a metal sensor surface. In the present study, the targetability of neonatal Fc receptor (FcRn) was studied by SPR. FcRn-mediated targetability studies were performed against protein A and human colorectal adenocarcinoma (Caco-2) immobilized on SPR sensors. The aim of the study was to confirm the FcRn targetability with bare Fc-fragment and Fc-fragment modified nanoparticles (NPs) designed for oral drug delivery. The NPs consisted of a core porous silicon (PSi) particle, entrapped into a lignin capsule, and finally functionalized with the FcRn-targeting ligand. Results confirmed the binding efficacy of bare Fc-fragment with protein A at pH 6.5, which was the critical pH value for preserving the lignin capsule around the PSi NPs. The cell-based SPR response was significantly higher for FcRn-targeted NPs when compared with non-functionalized NPs. According to these results, FcRn-mediated transcytosis emerges with great potential for oral drug delivery via Fc-functionalized NPs.
  • Li, Wei; Liu, Zehua; Fontana, Flavia; Ding, Yaping; Liu, Dongfei; Hirvonen, Jouni Tapio; Almeida Santos, Helder (2018)
    In the past two decades, porous silicon (PSi) has attracted increasing attention for its potential biomedical applications. With its controllable geometry, tunable nanoporous structure, large pore volume/high specific surface area, and versatile surface chemistry, PSi shows significant advantages over conventional drug carriers. Here, an overview of recent progress in the use of PSi in drug delivery and cancer immunotherapy is presented. First, an overview of the fabrication of PSi with various geometric structures is provided, with particular focus on how the unique geometry of PSi facilitates its biomedical applications, especially for drug delivery. Second, surface chemistry and modification of PSi are discussed in relation to the strengthening of its performance in drug delivery and bioimaging. Emerging technologies for engineering PSi-based composites are then summarized. Emerging PSi advances in the context of cancer immunotherapy are also highlighted. Overall, very promising research results encourage further exploration of PSi for biomedical applications, particularly in drug delivery and cancer immunotherapy, and future translation of PSi into clinical applications.
  • Li, Yunzhan; Liu, Zehua; Li, Li; Lian, Wenhua; He, Yaohui; Khalil, Elbadry; Makila, Ermei; Zhang, Wenzhong; Torrieri, Giulia; Liu, Xueyan; Su, Jingyi; Xiu, Yuanming; Fontana, Flavia; Salonen, Jarno; Hirvonen, Jouni; Liu, Wen; Zhang, Hongbo; Santos, Hélder A.; Deng, Xianming (2020)
    The analysis of nanoparticles' biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio-nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro-inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor kappa B pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.