Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled ...release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light‐triggered DDS relies on processes of photolysis, photoisomerization, photo‐cross‐linking/un‐cross‐linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high‐energy photons of UV/Vis light, recently nanocarriers have been developed based on light‐response to low‐energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light‐triggered drug release systems are normally achieved by using two‐photon absorption and photon upconversion processes. Herein, recent advances of light‐responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR‐light triggered drug delivery by two‐photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.
Photoresponsive nanomaterials for the development of targeted drug delivery systems have attracted tremendous research interests in the recent decade. Herein, recent advances of photoactivated nanocarriers for drug delivery are summarized, including the strategies for engineering of UV, visible and near infrared (NIR) light responsive nanosystems. Finally, research challenges and future directions are also discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cancer stem cells (CSCs) are a subpopulation of tumor cells that exhibit self-renewal, differentiation, and tumorigenicity. CSCs are highly resistant to the conventional cancer treatment and have ...been associated with metastasis. Several studies have been shown that salinomycin (Sal) has the potential to target cancer stem cells evidenced by in vitro and in vivo tumor models. Here, salinomycin was conjugated with biocompatible gold nanoparticles (AuNPs) coated with poly(ethylene glycol) to improve its specificity in targeting breast cancer stem cells (BCSCs). BCSCs derived from CD24low/CD44high subpopulation showed high sensitivity to Sal–AuNP treatment. An in-depth analysis on the mechanism of action of Sal–AuNPs indicated ferroptosis, an iron-dependent cell death, was achieved as a result of iron accumulation and inhibition of antioxidant properties. This also led to the induction of oxidative stress, mitochondrial dysfunction, and lipid oxidation. Our findings suggest Sal–AuNP treatment is an efficient therapeutic avenue in eliminating cancer stem cells.
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IJS, KILJ, NUK, PNG, UL, UM
APS exhibited in vitro and in vivo anti-tumor activity targeted macrophages and host immune system via immunoregulation.
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•APS was non-cytotoxic against 4T1 cells.•APS mediated ...macrophages inhibited the growth of 4T1 cells.•APS mediated macrophages induced cell apoptosis by mitochondrial pathway.•APS exhibited in vivo anti-tumor activity by immunoregulation.•APS alleviated immunosuppression of 5-FU on immune system.
Astragalus polysaccharide (APS) has attracted growing interests in the field of anti-cancer by direct killing effect and improving immune function. In this study, the structure and composition of APS was determined, following the evaluation of in vitro and in vivo anti-tumor activity of APS targeted macrophages and host immune system based on immunoregulated strategy. The results indicated that APS had no direct cytotoxicity against 4T1 cells, but APS mediated macrophages could significantly inhibit the growth of 4T1 cells by the induction of cell cycle arrest (G2 phase) and cell apoptosis. APS mediated macrophages promoted the apoptosis of 4T1 cells mainly through the mitochondrial apoptosis pathway. The in vivo findings demonstrated that APS could markedly improve the thymus index and spleen index, and restore the structure of the damaged thymus and spleen tissue. APS could significantly enhance the proliferation of spleen lymphocytes and increase phagocytosis of peritoneal macrophages in mice. Furthermore, APS was capable of up-regulating the expression of IL-2, TNF-α and IFN-γ in peripheral blood. APS combined with 5-FU could improve the anti-tumor effect accompanied by the immunosuppressive alleviation of 5-FU on immune system, which may be suitable as an immune adjuvant for chemotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Macrophages are essential immune cells and play a major role in the immune response as pro-inflammatory or anti-inflammatory agents depending on their plasticity and functions. Infiltration and ...activation of macrophages are usually involved in wound healing. Herein, we first described macrophage polarization and their critical functions in wound healing process. It is addressed how macrophages collaborate with other immune cells in the wound microenvironment. Targeting macrophages by manipulating or re-educating macrophages in inflammation using nanomedicines is a novel and feasible strategy for wound management. We discussed the design and physicochemical properties of nanomaterials and their functions for macrophages activation and anti-inflammatory signaling during wound therapy. The mechanism of action of the strategies and appropriate examples are also summarized to highlight the pros and cons of those approaches. Finally, the potential of nanomedicines to modulate macrophage polarization for skin regeneration is discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Studies have found that matrix metalloproteinase-9 (MMP-9) plays a significant role in cancer cell invasion, metastasis, and tumor growth. But it is a challenge to go for highly sensitive and ...selective detection and targeting of MMP-9 due to the similar structure and function of the MMP proteins family. Herein, a novel surface-enhanced Raman scattering (SERS) sensing strategy was developed based on the aptamer-induced SERS “hot spot” formation for the extremely sensitive and selective determination of MMP-9. To develop the nanosensor, one group of gold nanospheres was modified with MMP-9 aptamer and its complementary strand DNA1, while DNA2 (complementary to DNA1) and the probe molecule 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) were grafted on the surface of the other group of gold nanospheres. In the absence of MMP-9, DTNB located on the 13-nm gold nanospheres has only generated a very weak SERS signal. However, when MMP-9 is present, the aptamer preferentially binds to the MMP-9 to construct MMP-9–aptamer complex. The bare DNA1 can recognize and bind to DNA2, which causes them to move in close proximity and create a SERS hot spot effect. Due to this action, the SERS signal of DTNB located at the nanoparticle gap is greatly enhanced, achieving highly sensitive detection of MMP-9. Since the hot spot effect is caused by the aptamer that specifically recognizes MMP-9, the approach exhibits excellent selectivity for MMP-9 detection. Based on the benefits of both high sensitivity and excellent selectivity, this method was used to distinguish the difference in MMP-9 levels between normal and cancer cells as well as the expression of MMP-9 from cancer cells with different degrees of metastasis. In addition, this strategy can accurately reflect the dynamic changes in intracellular MMP-9 levels, stimulated by the MMP-9 activator and inhibitor. This strategy is expected to be transformed into a new technique for diagnosis of specific cancers related to MMP-9 and assessing the extent of cancer occurrence, development and metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Iron oxide nanoparticles (IONPs) have emerging anticancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, ...the underlying mechanism and structure–function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and down-regulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anticancer technologies.
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IJS, KILJ, NUK, PNG, UL, UM
This work developed a facile approach to fabricate highly sensitive and flexible polyurethane/graphene platelets composite film for wearable strain sensor. The composite film was fabricated via ...layer-by-layer laminating method which is simple and cost-effective; it exhibited outstanding electrical conductivity of 1430 ± 50 S/cm and high sensitivity to strain (the gauge factor is up to 150). In the sensor application test, the flexible strain sensor achieves real-time monitoring accurately for five bio-signals such as pulse movement, finger movement, and cheek movement giving a great potential as wearable-sensing device. In addition, the developed strain sensor shows response to pressure and temperature in a certain region. A multifaceted comparison between reported flexible strain sensors and our strain sensor was made highlighting the advantages of the current work in terms of (1) high sensitivity (gauge factor) and flexibility, (2) facile approach of fabrication, and (3) accurate monitoring for body motions.
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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
Gold nanoparticles are of high interest in the biodiagnostic and bioimaging field owing to their unique optical properties such as localized surface plasmon resonance (LSPR) and high Rayleigh ...scattering efficiency in the visible range. Although biofunctionalization is a prerequirement prior to their integration in diagnostic procedures, aggregation-free conjugation of biomacromolecules to large gold nanoparticle is not trivial. Here, a robust and simple method based on commercially available reactants is reported for the efficient biofunctionalization of gold nanoparticles with sizes ranging from 15 to 175 nm. It is demonstrated that mixed poly(ethylene glycol) (PEG) layers, prepared using specific ratios of low- and high-molecular-weight PEG chains, can be conjugated to proteins and monoclonal antibodies using standard carbodiimide chemistry without detectable aggregation. The properties of the mixed PEG interlayer modified gold nanoparticles were investigated using UV–vis spectrometer, dynamic light scattering, and X-ray photoelectron spectroscopy, which demonstrated the importance of controlling biointerfacial properties. Using the epithelial cell adhesion molecule (EpCAM) as a model target antigen, the benefit of the mixed PEG layers over coatings prepared using high-molecular-weight PEG chains only is demonstrated in vitro using bright field microscopy and reflectance confocal microscopy. Very high binding affinity to breast cancer cells was obtained for the mixed PEG layers. This robust procedure demonstrates that, under optimal conditions, a compromise can be achieved between the excellent steric protection provided by thick PEG adlayers and the high bioconjugation yields afforded by adlayers from low-molecular-weight tethers.
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IJS, KILJ, NUK, PNG, UL, UM
The lack of effective treatment for neurological disorders has encouraged the search for novel therapeutic strategies. Remarkably, neuroinflammation provoked by the activated microglia is emerging as ...an important therapeutic target for neurological dysfunction in the central nervous system. In the pathological context, the hyperactivation of microglia leads to neuroinflammation through the release of neurotoxic molecules, such as reactive oxygen species, proteinases, proinflammatory cytokines and chemokines. Cannabidiol (CBD) is a major pharmacologically active phytocannabinoids derived from Cannabis sativa L. CBD has promising therapeutic effects based on mounting clinical and preclinical studies of neurological disorders, such as epilepsy, multiple sclerosis, ischemic brain injuries, neuropathic pain, schizophrenia and Alzheimer’s disease. A number of preclinical studies suggested that CBD exhibited potent inhibitory effects of neurotoxic molecules and inflammatory modulators, highlighting its remarkable therapeutic potential for the treatment of numerous neurological disorders. However, the molecular mechanisms of action underpinning CBD’s effects on neuroinflammation appear to be complex and are poorly understood. This review summarises the anti-neuroinflammatory activities of CBD against various neurological disorders with a particular focus on their main molecular mechanisms of action, which were related to the downregulation of NADPH oxidase-mediated ROS, TLR4-NFκB and IFN-β-JAK-STAT pathways. We also illustrate the pharmacological action of CBD’s derivatives focusing on their anti-neuroinflammatory and neuroprotective effects for neurological disorders. We included the studies that demonstrated synergistic enhanced anti-neuroinflammatory activity using CBD and other biomolecules. The studies that are summarised in the review shed light on the development of CBD, including its derivatives and combination preparations as novel therapeutic options for the prevention and/or treatment of neurological disorders where neuroinflammation plays an important role in the pathological components.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nanoparticles are widely used in industry and personal care, and they inevitably end up in people's bodies and the environment. The widespread use of nanoparticles has raised new concerns about their ...neurotoxicity, as nanoparticles can enter the nervous system by blood-brain barrier. In neurotoxicity testing, the zebrafish provides powerful tools to overcome the limitations of other models. This paper will provide a comprehensive review of the power of zebrafish in neurotoxicity tests and the neurotoxic effects of nanoparticles, including inorganic, organic, and metal-based nanoparticles, on zebrafish from different perspectives. Such information can be used to predict not only the effects of nanoparticles on other species exposed to the aquatic environment but also the neurotoxicity of nanoparticles in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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