Tumour cell phagocytosis by antigen presenting cells (APCs) is critical to the generation of antitumour immunity. However, cancer cells can evade phagocytosis by upregulating anti-phagocytosis ...molecule CD47. Here, we show that CD47 blockade alone is inefficient in stimulating glioma cell phagocytosis. However, combining CD47 blockade with temozolomide results in a significant pro-phagocytosis effect due to the latter's ability to induce endoplasmic reticulum stress response. Increased tumour cell phagocytosis subsequently enhances antigen cross-presentation and activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in APCs, resulting in more efficient T cell priming. This bridging of innate and adaptive responses inhibits glioma growth, but also activates immune checkpoint. Sequential administration of an anti-PD1 antibody overcomes this potential adaptive resistance. Together, these findings reveal a dynamic relationship between innate and adaptive immune regulation in tumours and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.
Cell-penetrating peptides (CPPs) are short peptides (fewer than 30 amino acids) that have been predominantly used in basic and preclinical research during the last 30 years. Since they are not only ...capable of translocating themselves into cells but also facilitate drug or CPP/cargo complexes to translocate across the plasma membrane, they have potential applications in the disease diagnosis and therapy, including cancer, inflammation, central nervous system disorders, otologic and ocular disorders, and diabetes. However, no CPPs or CPP/cargo complexes have been approved by the US Food and Drug Administration (FDA). Many issues should be addressed before translating CPPs into clinics. In this review, we summarize recent developments and innovations in preclinical studies and clinical trials based on using CPP for improved delivery, which have revealed that CPPs or CPP-based delivery systems present outstanding diagnostic therapeutic delivery potential.
Intracellular delivery is a critical step in biological discoveries and has been widely utilized in biomedical research. A variety of molecular tools have been developed for cell-based gene ...therapies, including FDA approved CAR-T immunotherapy, iPSC, cell reprogramming and gene editing. Despite the inspiring results of these applications, intracellular delivery of foreign molecules including nucleic acids and proteins remains challenging. Efficient yet non-invasive delivery of biomolecules in a high-throughput manner has thus long fascinates the scientific community. As one of the most popular non-viral technologies for cell transfection, electroporation has gone through enormous development with the assist of nanotechnology and microfabrication. Emergence of miniatured electroporation system brought up many merits over the weakness of traditional electroporation system, including precise dose control and high cell viability. These new generation of electroporation systems are of considerable importance to expand the biological applications of intracellular delivery, bypassing the potential safety issue of viral vectors. In this review, we will go over the recent progresses in the electroporation-based intracellular delivery and several potential applications of cutting-edge research on the miniatured electroporation, including gene therapy, cellular reprogramming and intracellular probe.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
(1) Purpose: To improve the capability of EfficientNet, including developing a cropping method called Random Center Cropping (RCC) to retain the original image resolution and significant features on ...the images' center area, reducing the downsampling scale of EfficientNet to facilitate the small resolution images of RPCam datasets, and integrating attention and Feature Fusion (FF) mechanisms with EfficientNet to obtain features containing rich semantic information. (2) Methods: We adopt the Convolutional Neural Network (CNN) to detect and classify lymph node metastasis in breast cancer. (3) Results: Experiments illustrate that our methods significantly boost performance of basic CNN architectures, where the best-performed method achieves an accuracy of 97.96% ± 0.03% and an Area Under the Curve (AUC) of 99.68% ± 0.01% on RPCam datasets, respectively. (4) Conclusions: (1) To our limited knowledge, we are the only study to explore the power of EfficientNet on Metastatic Breast Cancer (MBC) classification, and elaborate experiments are conducted to compare the performance of EfficientNet with other state-of-the-art CNN models. It might provide inspiration for researchers who are interested in image-based diagnosis using Deep Learning (DL). (2) We design a novel data augmentation method named RCC to promote the data enrichment of small resolution datasets. (3) All of our four technological improvements boost the performance of the original EfficientNet.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Exosomes are attractive as nucleic-acid carriers because of their favourable pharmacokinetic and immunological properties and their ability to penetrate physiological barriers that are impermeable to ...synthetic drug-delivery vehicles. However, inserting exogenous nucleic acids, especially large messenger RNAs, into cell-secreted exosomes leads to low yields. Here we report a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides. We transfected various source cells with plasmid DNAs and stimulated the cells with a focal and transient electrical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptides. Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation produced up to 50-fold more exosomes and a more than 10
-fold increase in exosomal mRNA transcripts, even from cells with low basal levels of exosome secretion. In orthotopic phosphatase and tensin homologue (PTEN)-deficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced inhibition of tumour growth and increased survival. Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applications requiring transcriptional manipulation.
Photodynamic therapy (PDT) is able to non-invasively treat and diagnose various cancers and nonmalignant diseases by combining light, oxygen, and photosensitizers (PSs). However, the application of ...PDT is hindered by poor water solubility and limited light-penetration depth of the currently available photosensitizers (PSs). Water solubility of PSs is crucial for designing pharmaceutical formulation and administration routes. Wavelength of light source at visible range normally has therapeutic depth less than 1 mm. In this review, focus is on the recent research progress of metal-based nanoparticles being applied in PDT. The potential toxicity of these nanoscales and future directions are further discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The increasing demand for environmental protection has led to the rapid development of greener and biodegradable polymers, whose creation provided new challenges and opportunities for the advancement ...of nanomaterial science. Biodegradable polymer materials and even nanofillers (e.g., natural fibers) are important because of their application in greener industries. Polymers that can be degraded naturally play an important role in solving public hazards of polymer materials and maintaining ecological balance. The inherent shortcomings of some biodegradable polymers such as weak mechanical properties, narrow processing windows, and low electrical and thermal properties can be overcome by composites reinforced with various nanofillers. These biodegradable polymer composites have wide-ranging applications in different areas based on their large surface area and greater aspect ratio. Moreover, the polymer composites that exploit the synergistic effect between the nanofiller and the biodegradable polymer matrix can lead to enhanced properties while still meeting the environmental requirement. In this paper, a broad review on recent advances in the research and development of nanofiller reinforced biodegradable polymer composites that are used in various applications, including electronics, packing materials, and biomedical uses, is presented. We further present information about different kinds of nanofillers, biodegradable polymer matrixes, and their composites with specific concern to our daily applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
High-performance elastic and ultrathin electric heating materials were prepared by forced impregnation of polydimethylsiloxane (PDMS) matrix into multiwalled carbon nanotube (MWCNT) nanopaper (NP) by ...using an efficient two-step ultrasonication treatment technique. Morphological feature, stretchability, electrical property, and electric heating behavior of the MWCNT/PDMS nanocomposite film (NC film) were investigated. Scanning electron microscope images confirmed that the MWCNTs were well impregnated in PDMS matrix with no aggregations. Relatively high MWCNT content (> 10 wt%), which results from the compact stack structure within NPs, in the MWCNT/PDMS NC film guaranteed the high thermal conductivity and excellent electric heating behaviors with significantly improved uniformity. The small thermal capacitance of PDMS matrix and high thermal conductivity of MWCNTs enabled temperature response rapidity at constant applied voltages. The superior and stable heating–cooling cyclic performances (temperature responsiveness, electric power efficiency, and steady-state maximum temperature) of MWCNT/PDMS NC film made it an ideal option for actual electric heating applications.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A special issue of the journal Dose-Response entitled “Nanotechnology and Microtechnology in Drug Delivery Systems” is proposed. In pharmaceutical studies, new and existing drugs continue to be ...investigated for their poor specificity, solubility, therapeutic index, and immunogenicity. In order to solve these problems, drug delivery systems are essential for controlled drug release. It has been shown that the size and shape (nano- or micro-) of drug carriers can affect a drug’s circulation time, distribution, and cellular uptake. Hence, it is not surprising that nanotechnology and microtechnology have been explored as powerful tools for drug delivery in past decades. The main topics will be related to the technologies including microtechnology for the sustained release of drug, nanotechnology for the targeting delivery of drugs, new polymer materials nanotechnology, nanotechnology in drugs combination application, and so on.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Multifunctional electronics are attracting great interest with the increasing demand and fast development of wearable electronic devices. Here, we describe an epidermal strain sensor based on an ...all-carbon conductive network made from multi-walled carbon nanotubes (MWCNTs) impregnated with poly(dimethyl siloxane) (PDMS) matrix through a vacuum filtration process. An ultrasonication treatment was performed to complete the penetration of PDMS resin in seconds. The entangled and overlapped MWCNT network largely enhances the electrical conductivity (1430 S m−1), uniformity (remaining stable on different layers), reliable sensing range (up to 80% strain), and cyclic stability of the strain sensor. The homogeneous dispersion of MWCNTs within the PDMS matrix leads to a strong interaction between the two phases and greatly improves the mechanical stability (ca. 160% strain at fracture). The flexible, reversible and ultrathin (<100 m) film can be directly attached on human skin as epidermal strain sensors for high accuracy and real-time human motion detection.
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