Search

Nanosecond pulsed laser induced photoporation has gained increasing attention from scholars as an effective method for delivering the membrane-impermeable extracellular materials into living cells. Compared with femtosecond laser, nanosecond laser has the advantage of high throughput and low costs. It also has a higher delivery efficiency than continuous wave laser. Here, we provide an extensive overview of current status of nanosecond pulsed laser induced photoporation, covering the photoporation mechanism as well as various factors that impact the delivery efficiency of photoporation. Additionally, we discuss various techniques for achieving photoporation, such as direct photoporation, nanoparticles-mediated photoporation and plasmonic substrates mediated photoporation. Among these techniques, nanoparticles-mediated photoporation is the most promising approach for potential clinical application. Studies have already been reported to safely destruct the vitreous opacities in vivo by nanosecond laser induced vapor nanobubble. Finally, we discuss the potential of nanosecond laser induced phototoporation for future clinical applications, particularly in the areas of skin and ophthalmic pathologies. We hope this review can inspire scientists to further improve nanosecond laser induced photoporation and facilitate its eventual clinical application.

Photodynamic therapy (PDT) depends on the light-irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue-penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co-delivery of CRISPR-Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single-stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G-quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G-quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H 2 O 2 to O 2 , overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O 2 to 1 O 2 . The integration of gene editing and PDT allows substantial accumulation of 1 O 2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model., (© 2024 Wiley‐VCH GmbH.)

Enzyme cascade with high specificity and catalytic efficiency has significant applications for developing efficient bioanalysis methods. In this work, a sensitive and selective aptasensor was constructed based on the DNA-induced assembly of biocatalytic nanocompartments. Different from the conventional co-immobilization in one pot, the cascade enzymes of glucose oxidase (GOX) and horseradish peroxidase (HRP) were separately encapsulated in ZIF-90 nanoparticles. After conjugating complementary DNA or aptermer on enzyme@ZIF-90, DNA hybridization drove enzyme@ZIF-90 connected into clusters or linked on other DNA modified biocatalytic nanocompartment (such as invertase loaded Fe 3 O 4 @SiO 2 ). Owing to the shortened distance between enzymes, the catalytic efficiency of connected clusters was significantly enhanced. However, the specifically interaction between the substrate molecule and aptermer sequence would lead to the disassembly of DNA duplexes, resulting in the gradual "switching-off" of cascade reactions. With aflatoxin B1 (AFB1) as the model substrate, the compartmentalized three-enzyme nanoreactors showed good analytical performance in the linear range from 0.01 ng mL -1 to 50 ng mL -1 with a low detection limit (3.3 pg mL -1 ). In addition, the proposed aptasensor was applied to detect AFB1 in corn oil and wheat powder samples with total recoveries ranging from 94 % to 109 %. As a result, this DNA-induced strategy for enzyme cascade nanoreactors opens new avenues for stimuli-responsive applications in biosensing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Microplastics (MPs)/nanoplastics (NPs), as a source and vector of pathogenic bacteria, are widely distributed in the natural environments. Here, we investigated the combined effects of polystyrene NPs (PS-NPs) and lipopolysaccharides (LPS) on testicular function in mice for the first time. 24 male mice were randomly assigned into 4 groups, control, PS-NPs, LPS, and PS-NPs + LPS, respectively. Histological alterations of the testes were observed in mice exposed to PS-NPs, LPS or PS-NPs + LPS. Total sperm count, the levels of testosterone in plasma and testes, the expression levels of steroidogenic acute regulatory (StAR) decreased more remarkable in testes of mice treated with PS-NPs and LPS than the treatment with LPS or PS-NPs alone. Compared with PS-NPs treatment, LPS treatment induced more sever inflammatory response in testes of mice. Moreover, PS-NPs combined with LPS treatment increased the expression of these inflammatory factors more significantly than LPS treatment alone. In addition, PS-NPs or LPS treatment induced oxidative stress in testes of mice, but their combined effect is not significantly different from LPS treatment alone. These results suggest that PS-NPs exacerbate LPS-induced testicular dysfunction. Our results provide new evidence for the threats to male reproductive function induced by both NPs and bacterial infection in human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanoplastics, as a new class of environmental pollutants, have been frequently detected in environmental media and organisms. Monopterus albus (M. albus) is an important economic aquatic product with a high dietary consumption. However, the potential biological effects of nanoplastics on M. albus remain unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) at different concentrations (0, 0.5, 1, 5 and 10 mg/L) on M. albus were investigated using an untargeted metabolomics approach. The results showed that 59, 44, 24, and 31 individual differential metabolites and 16, 9, 6, and 2 significant differential metabolic pathways were significantly changed in 0.5, 1, 5, and 10 mg/L respectively, indicating the greater effect of PS-NPs at the relatively low concentrations. After further analysis, there are four same significant differential metabolic pathways for the 0.5 and 1 mg/L groups, i.e., ABC transporters, cAMP signaling pathway, Neuroactive ligand-receptor interaction, and Synaptic vesicle cycle. In addition, there was one mutual differential metabolic pathway (Neuroactive ligand-receptor interaction) among the four groups, indicative of the probably universal nervous influence of nanoplastics on M. albus. In a word, the current work suggests that PS-NPs might affect the nervous systems of M. albus through disturbing their liver metabolism, and nanoplastics at relatively low concentrations may possess a greater effect, which provides significant information for assessing the toxic effect and exposure risk of nanoplastics to organisms in aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu 2 MoS 4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB). Promotes the release of the cytotoxic substance reactive oxygen species (ROS) and the production of the immunogenic cell death (ICD) marker calreticulin (CRT) in KPC cells. CMS/PEG-B-P was also detected to have a certain activating effect on mouse immune cells, dendritic cells (mDC) and macrophage RAW264.7. Subcutaneous tumorigenicity experiments in C57BL/6 mice verified that CMS/PEG-B-P had an inhibitory effect on the growth of tumors and remodeling of the tumor immune microenvironment, including infiltration of CD4 + and CD8 + T cells and polarization of macrophages, as well as reduction of immunosuppressive cells. Meanwhile, CMS/PEG-B-P was found to have different effects on the release of cytokines in the tumor immune microenvironment, including The levels of immunostimulatory cytokines INF-γ and IL-12 are increased and the levels of immunosuppressive cytokines IL-6, IL-10 and IFN-α are decreased. In conclusion, nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that has a low response to single-drug immunotherapy with PD-L1 (CD274) inhibitors. We preared PEG-modified mesoporous nanomaterials Cu2MoS4 (CMS) loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. Our study demonstrated that Nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach., Competing Interests: Declaration Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo . In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.

Vascular disruption agent (combretastatin A-4 phosphate) and phototherapeutic (IEICO-4F) assembled nanoparticles (IFC NPs) were prepared for the first time. The IFC NPs have a high photo energy utilization efficiency of up to 96.1%, and could significantly inhibit tumor growth by photodynamic and photothermal therapy enhanced tumor vascular disruption.

An immunosuppressive tumor microenvironment (TME) with inadequate and exhausted tumor-infiltrating cytotoxic lymphocytes and abundant cellular immunosuppressors is the major obstacle responsible for the poor efficacy of PD-1/PD-L1 (programmed cell death 1 and its ligand 1) immune checkpoint blockade (ICB) therapy. Herein, a Janus silica nanoparticle (JSNP)-based immunomodulator is explored to reshape the TME for boosting the therapeutic outcomes of αPD-L1 therapy. The designed JSNP has two distinct domains, namely, an ultra pH-responsive side (UPS), which could encapsulate PI3Kγ inhibitor IPI549 in the pore structure, and a polycation-grafted intra-glutathione (GSH)-sensitive side (IGS), which could absorb CXCL9 cDNA on the surface. The final IPI549@UPS-IGS-PDMAEMA@CXCL9 cDNA (IUIPC) could release IPI549 in weak acid TME to target myeloid-derived suppressor cells (MDSCs) to reverse negative immunoregulation and then release CXCL9 cDNA in tumor cells with abundant GSH for sustained CXCL9 chemokine expression and secretion to improve cytotoxic lymphocyte recruitment signals, thereby jointly restoring tumor sensitivity to PD-1/PD-L1 ICB therapy. As expected, the IUIPC-mediated TME remodeling during αPD-L1 therapy significantly ameliorated TME immunosuppression, as well as induced potent systemic antitumor immune responses, which ultimately achieved a robustly boosted antitumor efficacy proven by remarkable suppression of primary tumor growth, obvious prevention of tumor recurrence, and significant regression of abscopal tumors. Hence, the IUIPC-mediated TME-regulating strategy provides an enormous perspective for the improvement of PD-1/PD-L1 ICB therapy.

The application of Epigallocatechin-3-gallate (EGCG) in food industry was limited by its low stability in aqueous solutions and poor bioavailability in vivo. The novel EGCG glycosylated arachin nanoparticles (Ara-CMCS-EGCG) and EGCG glycosylated casein nanoparticles (Cas-CMCS-EGCG) were prepared to improve the stability and bioavailability of EGCG. The effect of different variables on the storage stability and the slow-release behavior of novel glycosylation complexes in nanoparticle background solution and artificial gastrointestinal fluid were investigated. The results showed that the DPPH scavenging activity of Ara-CMCS-EGCG and Cas-CMCS-EGCG were stable in temperature (25 ∼ 70 °C). EGCG could enhance the crosslinking effect of molecular particles in glycosylation complexes solution. The glycosylated protein nanoparticles were stable to acid-base and enzymolysis in simulated gastrointestinal fluid. The release rate of EGCG in simulated intestinal fluid was higher than that in simulated gastric fluid. The glycosylated protein carrier can not only release EGCG slowly, but also significantly improve the stability and bioavailability of EGCG in simulated gastrointestinal fluid., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Many dyes or radioactive markers used for sentinel lymph node (SLN) have the shortcomings of false positive and radiation injury. Indocyanine green (ICG) seems to have a lower false positive rate and tissue damage, without a clear field of vision during the operation., Methods: For the shortcomings, we successfully synthesized three anionic pullulan materials, changed the degree of hydrophobic for size controlling (< 50nm) to prepare CHP nanoparticles (NPs) and changed the succinyl degree to prepare CHPC NPs with different negative surface potential., Results: The size of those NPs were less than 50nm under (transmission electron microscope) TEM, with hydrodynamic size of 90.67 ± 2.2 nm of CHP, 105.8 ± 1.7 nm of CHPC1 and 115.9 ± 2.3 nm of CHPC2. Moreover, the Zeta potential of CHP, CHPC1 and CHPC2 were -1.9 ± 0.2 mV, -9.6 ± 0.3 mV and -19.4 ± 0.7 mV. The size of ICG-loading CHP, CHPC1 and CHPC2 NPs increased to 109.4 ± 2.7 nm, 113.8 ± 1.2 nm and 30.6 ± 3.5 nm, as the zeta potential decreased to -2.7 ± 0.4 mV, -12.5 ± 1.6 mV and -23.1 ± 1.2 mV. With the increasing degree of succinyl, the size increased and the zeta potential decreased. At the same time, the higher degree of succinyl drug-loading NPs have lower release and have increased the stability of ICG. We found that the blank-NPs had no significant toxicity to normal cells (HSF), as the ICG@CHP group had larger toxicity than the CHPCs and control. Moreover, the cellular uptake was decreased with the increased degree of succinyl., Conclusion: In this study, we successfully prepared CHPC2 carriers with the maximum negative surface charge, for follow-up research and providing new ideas for SLN., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The development of novel nanozymes is of great importance for the efficient analysis of biomolecules such as H 2 O 2 , glucose, and antioxidants in the diagnosis of some diseases. Herein, novel nanozymes based on Fe nanoparticles (NPs) encapsulated in 2D carbon nanosheets (denoted as Fe@CNs) were constructed and employed in the field of biosensing. Notably, Fe@CNs have intrinsic dual mimic enzyme properties. The colorless colorimetric substrate 3,3',5,5'-tetramethylbenzidine (TMB) can be oxidized by Fe@CNs as oxidase- and peroxidase-like nanozymes, respectively. The generation of the oxidation state TMB (oxTMB) resulted from the presence of reactive oxygen species (ROS) which were produced by the catalytic decomposition of the dissolved oxygen or H 2 O 2 . Thus, a simple colorimetric biosensor was proposed to detect glutathione (GSH), H 2 O 2 , and glucose. In addition, the Fe@CN-based nanozymes also have excellent reusability in enzymatic catalysis. After separating from the sensing systems, Fe@CNs can be reused in other catalytic processes. This colorimetric method could be used as a universal sensing platform for the detection of antioxidants and H 2 O 2 -related bioanalysis. This work broadens the application of novel nanozymes in biosensing.

Triple-negative breast cancer (TNBC) is a form of breast cancer that is more aggressive and harder to treat than others, with a higher probability of relapse. Its nefarious capabilities for migrating and invading other parts of the body together with the current lack of clinically established effective therapies account for a low survival rate. In this work, we demonstrate the in-tandem use of two complementary therapeutic routes to effectively combat TNBC. A versatile magnetic-photothermal converter (MPC) consisting of zinc-doped ferrite nanoparticles and polyethene glycol, is shown to display excellent therapeutic efficiency, being capable to fight TNBC via two distinct routes: magneto-mechanical force (MMF) and near-infrared-II (NIR-II) hypothermal ablation. The combined use of these two complementary and synergistic therapies, which are less aggressive to the human body compared to conventional chemotherapeutic approaches, results in the splendid suppression of TNBC migration and invasion. Remotely controlling the MPCs by an external magnetic field, results in cellular MMF effects that cause direct mechanical destruction to the cancer cell membrane, leading to its necrosis. Furthermore, the MMF disrupts intracellular lysosomes, thereby triggering the release of large amounts of protein hydrolases, which induce intracellular oxidative stress, and accelerate the induction of apoptosis. Complementing the therapeutic approach based on MMF, the excellent photothermal performance of the MPC in the NIR-II region (1064 nm) is exploited to enable effective hypothermal ablation of the tumours, which can be achieved in deep tissue layers. The proposed multifunctional nanocomposites, together with the demonstrated "double-punch" therapeutic approach, hold significant potential to pave the way for future cutting-edge weapons against the dreadful TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Exploring a chemical imaging tool for visualizing the endogenous CO biosignaling molecule is of great importance in understanding the pathophysiological functions of CO in complex biological systems. Most of the existing CO fluorescent probes show excitation and emission in the region of ultraviolet and visible light, which are not suitable for application in in vivo deep-depth imaging of CO. Herein, a new near-infrared (NIR) to NIR upconversion luminescence (UCL) nanosystem for in vivo visualization of CO was developed, which possesses the merits of high selectivity and sensitivity, a deep tissue penetration depth, and a high signal-to-noise ratio. In this design, upon interaction with CO, the maxima absorption peak of the nanosystem showed a significant blue shift from 795 nm to 621 nm and triggered a remarkable turn-on NIR UCL signal due to the luminescence resonance energy transfer process. Leveraging this nanosystem, we achieved an NIR UCL visualization of the generation of CO biosignals caused by hypoxic, acute inflammation, or ischemic injury in living cells, zebrafish, and mice. Moreover, the protective effect of CO in zebrafish models of oxygen and glucose deprivation/reperfusion (OGD/R) and mice models of lipopolysaccharide-induced oxidative stress (LOS) and hepatic ischemia/reperfusion (HI/R) was also further verified. Therefore, this work discloses that the nanosystem not only serves as a promising nanoplatform to study biological signaling pathways of CO in pathophysiological events, but may also provide a powerful tool for HI/R injury diagnosis.

The possibility to precisely control important properties of nanoparticles (NPs) such as their size, morphology, surface charge, or doping content is crucial for enhancing the performance of existing solutions beyond the state-of-the-art and for enabling novel applications. In this work, custom-tailored Zn x Fe 3- x O 4 NPs are synthesized at different Zn doping concentrations to augment and expand their usefulness for high-performance applications in nanomedicine. By precisely increasing the Zn 2+ content in the range of 0 ≤ x ≤ 2.0, the discussed NPs can sequentially acquire valuable properties enabling magnetic resonance imaging, near-infrared (NIR) photothermal effects, NIR photocatalytic and photoelectric effects, depending on the variation of substitution position of the Zn 2+ in the magnetite structure and the emergence of a ZnO/ZnFe 2 O 4 heterostructure at high doping concentrations. The presented work demonstrates and explainsa facile route for the synthesis and modulation of multifunctional nanomaterials with manifold roles in disease diagnostics and therapy, and provides helpful guidance in designing divalent transition metal ion-doped nanomaterials., (© 2022 Wiley-VCH GmbH.)

Carbon monoxide (CO) is considered as the second gasotransmitter involved in a series of physiological and pathological processes. Although a number of organic fluorescent probes have been developed for imaging CO, these probes display excitation within the ultraviolet or visible range, which restrict their applications in the complex biosystems. In the present work, a strategy is developed to construct an upconversion nanoparticles-based nanosystem for upconversion luminescent (UCL) sensing CO. This nanosystem exhibits a fast response to CO with high sensitivity and selectivity in aqueous solution by a near-infrared-excited ratiometric UCL detection method. Meanwhile, laser scanning upconversion luminescence microscope experiments demonstrate that this nanosystem can visualize the endogenous CO bio-signaling in living cells, deep tissues, zebrafish, and living mice by ratiometric UCL imaging. In particular, this nanosystem has been successfully employed in visualization of the endogenous CO bio-signaling through up-regulation of heme oxygenase-1 (HO-1) in the progression of hypoxia, acute inflammation, or ischemic injury. This work demonstrates that the outstanding performance of the nanosystem not only can provide an effective tool for further understanding the role of CO in the physiological and pathological environment, but also may have great potential ability for tracking the expression of HO-1 in living systems., (© 2022 Wiley-VCH GmbH.)

Nanoparticles are widely used in biological research and cancer therapy. In hepatocellular carcinoma, several nanoplatforms have been synthesized and studied to improve the drug efficacy; however, these nanoplatforms are still insufficient to eradicate tumors. Herein, we have synthesized a novel vanadium (V)-iron-oxide (ION) nanoparticle (VIO) that combines chemodynamic, photothermal, and diagnostic capacities to enhance the tumor suppression effect in one agent with multiple functions. In the in vitro models, hepatocellular carcinoma cells are significantly inhibited by VIO-based nanoagents. The mechanistic study validates that VIO increases reactive oxygen species (ROS), which led to apoptosis and ferroptosis resulting in cell death. To our surprise, VIO targets not only tumor cells but also endothelial cells. In addition to inducing cell death, VIO also blocks tube formation and cell migration in human umbilical vein endothelial cell (HUVEC) and C166 models, indicating an antiangiogenic potential. In mouse tumor models, VIO retards tumor growth and induces apoptosis in tumor tissues. Furthermore, a significant blood vessel regression is seen in VIO-treated groups accompanied with larger necrotic areas. More interestingly, the activation of photothermal therapy completely eradicates tumor tissues. Taken together, this VIO nanoplatform could be a powerful anticancer candidate for nanodrug development.

Although microRNA-153-3p (miR-153-3p) has been demonstrated to confer protective roles in ischemia/reperfusion injury, its potential role in myocardial infarction (MI) remains undefined. Small-molecule modifiers and nanoparticles loaded with microRNAs (miRNAs) have emerged as potential therapeutic reagents for MI treatment. In this study, we prepared liposome nanoparticles, hyaluronic acid (HA)-cationic liposomes (CLPs) complex, for the delivery of miR-153-3p and delineated the mechanistic actions of miR-153-3p modified by nHA-CLPs in MI-induced injury. Our data suggested that nHA-CLPs-loaded miR-153-3p protected cardiomyocytes against MI-induced cardiomyocyte apoptosis and myocardial injury. miR-153-3p was bioinformatically predicted and experimentally verified to bind to Krüppel-like factor 5 (KLF5) 3'UTR and negatively regulate its expression. Hypoxia was adopted to stimulate MI-induced injury to cardiomyocytes in vitro, in which miR-153-3p presented anti-apoptotic potential. However, restoration of KLF5 reversed this anti-apoptotic effect of miR-153-3p. Furthermore, KLF5 was demonstrated to be an activator of the NF-κB pathway. KLF5 enhanced cardiomyocyte apoptosis and inflammation under hypoxic conditions through NF-κB pathway activation, while nHA-CLPs-loaded miR-153-3p suppressed inflammation by blocking the NF-κB pathway. Collectively, our findings suggested the cardioprotective role of miR-153-3p against MI and the successful delivery of miR-153-3p by nHA-CLPs. The identification of KLF5-mediated activation of NF-κB pathway as an apoptotic and inflammatory mechanism aids in better understanding of the biology of MI and development of novel therapeutic strategies for MI.

Incorporating multiple molecular interactions within a system to realize the metabolic reprogramming of cancer cells is prospected to be of great potential in cancer therapy. Herein, we report a supramolecular self-assembled DNA nanosystem, which reprogrammed the cellular antioxidant system via synergistic chemical and gene regulations. In the nanosystem, amphipathic telluroether was coordinated with Mn II to self-assemble into micelle, on which a siNrf2 integrated DNA network was assembled. The great electron-donating capability of telluroether was revealed to greatly promote Mn II -based Fenton-like reaction to generate subversive . OH in cancer cells. In response to adenosine triphosphoric acid, the siNrf2 was specially released in cytoplasm for down-regulating expression of detoxification enzymes, which enhanced chemocatalysis-mediated oxidative stress in cancer cells, thus significantly suppressing tumor progression., (© 2021 Wiley-VCH GmbH.)

Photothermal therapy (PTT), as a promising antineoplastic therapeutic strategy, has been harnessed to restrain tumor growth through near-infrared (NIR) irradiation mediated thermal ablation. Nevertheless, its biological applications are hampered by thermal diffusion and up-regulated heat shock proteins (HSPs). Herein, a versatile nanotheranostic agent is developed via integrating Zn 0.2 Fe 2.8 O 4 nanoparticles (NPs), polydopamine (PDA), and MnO 2 NPs for T 1/ T 2 dual-modal magnetic resonance (MR) imaging-guided and self-augmented PTT. The as-designed Zn 0.2 Fe 2.8 O 4 @PDA@MnO 2 NPs adequately serve as a PTT agent to realize effective photothermal conversion and obtain local hyperthermia. Additionally, the Zn 0.2 Fe 2.8 O 4 @PDA@MnO 2 NPs can significantly consume overexpressed glutathione (GSH) and generate Mn 2+ in the tumor microenvironment (TME), thus destroying redox homeostasis and catalytically generating hydroxyl radicals (˙OH) for HSP suppression and PTT enhancement. Meanwhile, Mn 2+ and Zn 0.2 Fe 2.8 O 4 NPs significantly strengthen T1- and T2-weighted MR contrast for tumor imaging and PTT guidance. Hence, this study offers proof of concept for self-augmented PTT and T 1/ T 2 dual-modal MR imaging for tumor elimination.

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As 0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with β-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided., (© 2021 Wiley-VCH GmbH.)

To develop efficient photoactive agents with satisfactory fluorescence, photodynamic, and photothermal effects is crucial for a phototherapeutic strategy to combat cancer diseases and pathogenic microbes. Herein, a water-soluble donor-acceptor-donor (D-A-D) structured conjugated oligomer was designed and synthesized, consisting of two cyclopenta-dithiophene (CDT) units as the electron donor and boron dipyrromethene (BODIPY) as the electron acceptor. Upon excitation, dual emission was observed for CDT-BODIPY with blue and red fluorescence peaks at 463 nm and at 730 nm, respectively, which was ascribed to intramolecular charge transfer (ICT). Due to the ICT effect, the singlet-to-triplet intersystem crossing rate of CDT-BODIPY was also enhanced, leading to an outstanding photodynamic behavior to produce reactive oxygen species (ROS). Meanwhile, its low bandgap also enabled it a moderate photothermal capability with a conversion efficiency of 33.1%. Taking advantage of its phototriggered activities, this conjugated oligomer exhibited an effective inhibition behavior on the pathogenic growth of Escherichia coli ( E. coli ), Staphylococcus aureus ( S. aureus ), and Candida albicans ( C. albicans ), which can be guided by dual-wavelength fluorescence imaging. This D-A-D type conjugated oligomer with balanced photophysical characteristics provides a promising strategy to imaging-guided photoactive therapy.

Given the diversity, complexity, and heterogeneity of persistent tumors, traditional nanoscale monotherapeutic systems suffer from dissatisfactory curative efficiency with incidence of metastasis or relapse. In parallel, the trend of clinical research on the basis of nanomedicines has increasingly shifted from monotherapy toward combinatorial therapy for admirable synergetic performances. In this regard, cutting-edge nanomedicines harnessing photothermal-chemodynamic bimodal therapy (PTT/CDT) have opened up a highly-efficient and relatively-safe cancer theranostic paradigm. Still, the integration of PTT/CDT functional units into one nanomedicine remains a herculean but meaningful task to achieve notable super-additive effects. This review aims to elucidate underlying synergistic interactions of PTT/CDT and highlight intriguing designs of nanomedicines for PTT/CDT including nanomaterial selection, performance optimization, multimodal therapy, visualization strategies, and targeting strategies. Furthermore, an outlook on further improvements of PTT/CDT is provided, emphasizing significant scientific issues that require remediation for clinical translation. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2020 Wiley Periodicals LLC.)

MicroRNA (miRNA) represents a promising class of therapeutic nucleic acid drugs, while delivery challenges remain that impede the advancement of miRNA therapy, largely because of in vivo instability and low delivery efficiency. Herein, we discover the dual roles of metal-organic framework (MOF) nanoparticles (ZIF-8) as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. The miR-34a-m@ZIF-8 complex demonstrated efficient cellular uptake and lysosomal stimuli-responsive miRNA release. Zn 2+ triggered the generation of reactive oxygen species, which consequently induced apoptosis of tumor cells. Released miR-34a-m led to a remarkable decrease in expression of Bcl-2 at both mRNA and protein levels and enhanced cancer cell apoptosis. In vivo experiments showed high efficacy of using miR-34a-m@ZIF-8 to suppress tumor growth via synergistic gene/chemodynamic therapy in a mouse model of triple-negative breast cancer. Our work demonstrates MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy.

Flexible paper-based nanocomposites dielectrics are of crucial importance in electrical insulation and advanced electrical power systems. In this work, a novel nanofibrillated cellulose/aramid fibrid (NFC/AF) composite was fabricated by vacuum-assisted filtration process. In order to improve the dielectric property of the composites, carboxylated nano-SiO 2 was chemically coated onto aramid fibrid via molecular self-assembly with the aid of phosphoric acid (PA) pretreatment and subsequent polyethyleneimine (PEI) functionalization. It was found that composites prepared by NFC and (PEI/SiO 2 )-modified AF (after crosslinking) ((PEI/SiO 2 )-AF) showed dense structure, which was mainly due to enhanced interfacial interaction between AF and NFC. Consequently, NFC/(PEI/SiO 2 )-AF paper-based composites showed better tensile toughness (∼6 % elongation at break) and mechanical strength (∼36.28 MPa), in comparison with NFC/AF. More importantly, the electrical insulation performance and thermal stability of the composites were significantly improved. Accordingly, this work provides a facile approach to fabricate high-performance dielectric composites especially for high-temperature electrical insulation applications., Competing Interests: Declaration of Competing Interest We declare that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Silica nanoparticles (SiNPs) are one of the most widely used types of nanoparticles across many industrial sectors, and are known to be present in the air year-round. In this study, we aimed to evaluate the potential adverse effects of SiNP exposure on pulmonary epithelial tight junctions, which serve as a critical barrier between the respiratory system and the circulatory system. In vivo studies confirmed that SiNPs decreased the protein expression levels of zonula occludens 1 (ZO-1), zonula occludens 2 (ZO-2), and occludin in the lungs of C57BL/6 mice. In vitro studies showed that SiNPs not only decreased the mRNA and protein expression of ZO-1 and ZO-2, but also decreased the protein expression of occludin in human bronchial epithelial (BEAS-2B) cells. In addition, SiNP exposure increased reactive oxygen species (ROS) production and activated extracellular regulated protein kinases (ERKs) and c-Jun N-terminal kinase (JNK). The inhibition of ROS and ERKs effectively protected the SiNP-induced downregulation of ZO-1 mRNA and protein expression, but had no effect on ZO-2 or occludin expression. SiNP-induced matrix metalloproteinase 9 (MMP9) protein expression appeared to be involved in occludin proteolytic degradation, in addition to SiNP-induced direct occludin protein degradation. The present study suggests that SiNPs disturb pulmonary epithelial tight junction structure and function via the ROS/ERK pathway and protein degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Poor deep tumor penetration and incomplete intracellular drug release remain challenges for antitumor nanomedicine application in clinical settings. Herein, a nanomedicine (RLPA-NPs) is developed that can achieve prolonged blood circulation, deep tumor penetration, active-targeting of cancer cells, endosome/lysosome escape, and intracellular selectivity self-amplified drug release for effective drug delivery. The RLPA-NPs are constructed by encapsulation of a pH-sensitive polymer octadecylamine-poly(aspartate-1-(3-aminopropyl) imidazole) (OA-P(Asp-API)) and a ROS-generation agent, β-Lapachone (Lap), in micelles assembled by the tumor-penetration peptide internalizing RGD (iRGD)-modified ROS-responsive paclitaxel (PTX)-prodrug. iRGD could promote RLPA-NPs penetration into deep tumor tissue, and specific targeting to cancer cells. After internalization by cancer cells through receptor-mediated endocytosis, OA-P(Asp-API) can rapidly protonate in the endosome's acidic environment, resulting in RLPA-NPs escape from the endosome through the "proton sponge effect". At the same time, the RLPA-NPs micelle disassembles, releasing Lap and PTX-prodrug. Subsequently, the released Lap could generate ROS, consequently amplifying and accelerating PTX release to kill tumor cells. The in vitro and in vivo studies demonstrated that RLPA-NPs can significantly improve the therapeutic effect compared to control groups. Therefore, RLPA-NPs are a promising nanoplatform for overcoming multiple physiological and pathological barriers to enhance drug delivery., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Atherosclerosis is a chronic progressive disease, which may result in serious clinical outcomes, such as acute heart events or stroke with high mortality. At present, the clinical problems of atherosclerosis mainly consist of the difficulty in confirming the plaques or identifying the stability of the plaques in the early phase and the shortage of valid treatments. Fortunately, with the development of nanotechnology, various inorganic nanoparticles with imaging enhancement and noninvasive therapy functions have been studied in the imaging and treatment of atherosclerosis, which has brought new hope to patients. This review focuses on the recent progress in the use of inorganic nanoparticles in the diagnosis and therapy of atherosclerosis, including the key processes in the development of atherosclerosis and the mainly involved cells, inorganic nanoparticle-based dual-mode imaging methods classified by the types of targeting cells, and inorganic nanoparticle-based therapeutic approaches, such as photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), drug delivery, gene therapy and imaging-guided therapy for atherosclerosis. Finally, this review discusses the challenges and directions of inorganic nanoparticles in potential clinical translation of anti-atherosclerosis in future. We believe this review will enable readers to systematically understand the progress of the inorganic nanoparticle-based imaging and therapy of atherosclerosis and therefore promote the further development of anti-atherosclerosis.

Understanding the influencing factors on the reaction kinetics of P450 BM3 within confined spaces is essential for developing efficient P450 BM3 bioreactors. Herein, two dendritic mesoporous silica nanoparticles (OH-DMSNs and NH 2 -DMSNs) with similar pore size but opposite surface charge have been prepared and served as the vehicle to immobilize P450 BM3. With the help of the film-forming material of chitosan, P450 BM3/OH-DMSN and P450 BM3/NH 2 -DMSN composites were immobilized on GC electrode and characterized with electrochemical measurements. Compared with P450 BM3/OH-DMSNs/GCE, P450 BM3/NH 2 -DMSNs/GCE showed higher electron transfer efficiency with higher current charge and lower k s value. Besides, the generated catalytic current towards testosterone on P450 BM3/NH 2 -DMSNs/GCE was 1.81 times larger than P450 BM3/OH-DMSNs/GCE. Furthermore, P450 BM3 inside NH 2 -DMSNs displayed higher affinity towards testosterone with the lower K m app value of 244.82 μM. These results are attributed to the positively charged internal walls of NH 2 -DMSNs so that P450 BM3 adapts to an orientation favorable for electron exchange with electrodes and substrate binding with the active sites. The present study provides fundamentals for regulating the surface charge to optimize redox process and catalytic behavior in CYP bioreactors through electrostatic interactions.

Carrier-free nanodrug via small-molecule assembly is a promising alternative strategy for tumor therapy. Thus, developing a self-recognizing carrier-free nanodrug without introduction of foreign ligand is very attractive to meet both targeting and therapeutic requirements while reducing structural complexity. Here we fabricated a tumor microenvironment-activated self-targeting nanodrug, via co-assembly of hydroxycamptothecin (HCPT) and bi-functional methotrexate (MTX, not only has antitumor effect but also shows innate affinity towards folate receptors) followed by surface covering through acidity-responsive polyethylene glycol (PEG). Notably, the morphology and size of MTX-HCPT nanodrug could be tuned by varying the drug-to-drug ratio and assembly time. The PEG shell of our nanodrug could be detached in response to acidic tumor microenvironment, and then MTX could be exposed for self-targeting to enhance tumor cell uptake. Subsequently, the shell-detached nanodrug could be dissociated in relatively stronger acidic lysosomal environment, resulting in burst release of both drugs. Further in vitro and in vivo studies demonstrated that our nanodrug showed a ~2.98-fold increase in cancer cell uptake, a ~1.25-fold increase in drug accumulation at tumor site, a significantly lower CI 50 value of ~0.3, a ~27.3% improvement in tumor inhibition comparing with the corresponding non-responsive nanodrug. Taken together, the here reported tumor microenvironment-activated self-recognizing nanodrug might be an extremely promising strategy for synergistically enhancing chemotherapy efficiency with minimized side effects., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A broad range of investigation methods and frameworks are currently used to throughly study the elasticity of various types of micro/nanoparticles (MNPs) with different properties and to explore the effect of such properties on their interactions with biological species. Specifically, the elasticity of MNPs serves as a key influencing factor with respect to important aspects of phagocytosis, such as the clathrin-mediated phagocytosis, caveolae-mediated phagocytosis, macropinocytosis, and cell membrane fusion. Achieving a clear understanding of the relationships that exist between the elasticity of MNPs and their phagocytic processes is essential to improve their performance in drug delivery, which is related to aspects such as circulation lifetime in blood, accumulation time in tissues, and resistance to metabolism. Resolving such aspects is very challenging, and related efforts require using the right tools/methods, which are not always easy to identify. This review aims to facilitate this by summarizing and comparing different cell phagocytosis pathways, while considering various MNPs exhibiting different elastic properties, shape change capabilities, and their effect on cellular uptake. We conduct an overview of the advantages exhibited by different MNPs with respect to both in vitro and in vivo delivery, taking computational simulation analysis and experimental results into account. This study will provide a guide for how to investigate various types of MNPs in terms of their elastic properties, together with their biomedical effects that rely on phagocytosis.

Due to the increasing scientific and biomedical interest in various nanoparticles (NPs) with excellent properties and the onset of their commercial use, a convenient and adjustable physical method for improved efficiency needs to be used for enabling their tech-scale production. Recently, great progress has been made in the large-scale production of NPs with a simple structure by pulsed laser ablation in liquid (PLAL). In this work, we synthesized gold-silica core-shell NPs by improved PLAL and provided a guide on how to investigate their physico-chemical properties and association with biological effects towards cancer photothermal therapy (PTT). By means of this method, reproducible and scalable liquid phase NPs with less toxicity and good stability can be realized for tech-scale production based on its further adjustment and modification. Moreover, a more complete investigation of the associations between the physico-chemical properties of functional NPs with complex structure and their biological effects may enable more targeted NPs towards specific requirements of biomedical applications.

Exploring novel surface-enhanced Raman scattering (SERS) active materials with high detection sensitivity, excellent biocompatibility, low biotoxicity, and good spectral stability is urgently required for efficacious cancer cell diagnosis. Herein, black TiO 2 nanoparticles (B-TiO 2 NPs) with crystal-amorphous core-shell structure are successfully developed. Remarkable SERS activity is derived from the synergistic effect of the promising crystal-amorphous core-shell structure. Abundant excitons can be generated by high-efficiency exciton transitions in the crystal core, a feature that provides sufficient charge source. Significantly, the novel crystal-amorphous heterojunction enables the efficient exciton separation at the crystal-amorphous interface, which can effectively facilitate charge transfer from the crystal core to the amorphous shell and results in exciton enrichment at the amorphous shell. Kelvin probe force microscopy (KPFM) confirms the Fermi level of the amorphous layer shifting to a relatively low position compared to that of the crystal core, allowing efficient photoinduced charge transfer (PICT) between the amorphous shell and probe molecules. The first-principles density functional theory (DFT) calculations further indicate that the amorphous shell structure possesses a narrow band gap and a relatively high electronic density of state (DOS), which can effectively promote vibration coupling with target molecules. Moreover, MCF-7 drug-resistant (MCF-7/ADR) breast cancer cells can be quickly and accurately diagnosed based on the high-sensitivity B-TiO 2 -based SERS bioprobe. To the best of our knowledge, this is the first time the crystal-amorphous core-shell heterojunction enhancement of the TiO 2 -molecule PICT process, which widens the application of semiconductor-based SERS platforms in precision diagnosis and treatment of cancer, has been investigated.

Metastasis is the primary cause of cancer morbidity and mortality. To obtain an effective diagnosis and treatment, precise imaging of tumor metastasis is required. Here we prepared persistent luminescent nanoparticles (PLNPs) containing a hydrogel (PL-gel) for targeted, sustained, and autofluorescence-free tumor metastasis imaging. PLNPs offered renewable long-lasting near-infrared (NIR) emitting without in situ radiation, favoring deep tissue penetration imaging without background interference. PLNPs were conjugated with 4-carboxyphenyl boronic acid (CPBA) to yield PLNPs-CPBA, which specifically recognized metastatic breast cancer cells (MBA-MD-231 cells) and enabled receptor-mediated endocytosis for specific cancer cell labeling. The PLNPs-CPBA-labeled cancer cells enabled sensitive imaging performance and high viability without influencing the migration and invasiveness of cancer cells for long-term tracking. PLNPs-CPBA were further encapsulated inside alginate to generate PL-gel for sustained PLNPs-CPBA release and tumor cell labeling, and the PL-gel showed enhanced renewable persistent luminescence compared to the PLNPs-CPBA suspension. The metastasis in the mouse breast cancer model was continuously tracked by persistent luminescence imaging, showing that PL-gel achieved noninvasive and highly selective imaging of tumor metastasis without background interference. Our PL-gel could be rationally designed to specifically target other types of cancer cells and thus provide a powerful and generic platform for the study of tumor metastasis.

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT-induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal-organic framework (MOF)-based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF-based nanoparticles are self-assembled from H 2 TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN-ACF-CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF-1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT-based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune-responses both in vitro and in vivo, which may have great potential for clinical translation in future., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Advantages such as strong signal strength, resistance to photobleaching, tunable fluorescence emissions, high sensitivity, and biocompatibility are the driving forces for the application of fluorescent nanoparticles (FNPs) in cancer diagnosis and therapy. In addition, the large surface area and easy modification of FNPs provide a platform for the design of multifunctional nanoparticles (MFNPs) for tumor targeting, diagnosis, and treatment. In order to obtain better targeting and therapeutic effects, it is necessary to understand the properties and targeting mechanisms of FNPs, which are the foundation and play a key role in the targeting design of nanoparticles (NPs). Widely accepted and applied targeting mechanisms such as enhanced permeability and retention (EPR) effect, active targeting, and tumor microenvironment (TME) targeting are summarized here. Additionally, a freshly discovered targeting mechanism is introduced, termed cell membrane permeability targeting (CMPT), which improves the tumor-targeting rate from less than 5% of the EPR effect to more than 50%. A new design strategy is also summarized, which is promising for future clinical targeting NPs/nanomedicines design. The targeting mechanism and design strategy will inspire new insights and thoughts on targeting design and will speed up precision medicine and contribute to cancer therapy and early diagnosis., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Efficient tumor targeting has been a great challenge in the clinic for a very long time. The traditional targeting methods based on enhanced permeability and retention (EPR) effects show only an ≈5% targeting rate. To solve this problem, a new graphene-based tumor cell nuclear targeting fluorescent nanoprobe (GTTN), with a new tumor-targeting mechanism, is developed. GTTN is a graphene-like single-crystalline structure amphiphilic fluorescent probe with a periphery that is functionalized by sulfonic and hydroxyl groups. This probe has the characteristic of specific tumor cell targeting, as it can directly cross the cell membrane and specifically target to the tumor cell nucleus by the changed permeability of the tumor cell membranes in the tumor tissue. This new targeting mechanism is named the cell membrane permeability targeting (CMPT) mechanism, which is very different from the EPR effect. These probes can recognize tumor tissue at a very early stage and track the invasion and metastasis of tumor cells at the single cell level. The tumor-targeting rate is improved from less than 5% to more than 50%. This achievement in efficient and accurate tumor cell targeting will speed up the arrival of a new era of tumor diagnosis and treatment., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The advent of personalized medicine has brought an increased interest in personal health among general consumers. As a result, there is a great need for user-centric point-of-care (POC) health devices. Such devices are equally pertinent in developing countries or resource-limited settings for performing diagnostic tests. However, current POC tests for diseases such as human immunodeficiency virus (HIV) or leukocytosis do not provide adequate levels of sensitivity or do not exist at all. Here, we extend our mobile magneto-nanosensor platform to point-of-care HIV and leukocytosis detection. The platform can be multiplexed, and the circuitry enables portability and sensitivity in the POC setting. A smartphone application simplifies operation and provides guidance to facilitate self-testing. Commercially available POC test kits typically provide only qualitative or semi-quantitative results of a single analyte. The magneto-nanosensor platform can provide users with pleasant user-experience while demonstrating robust sensitive and specific multiplexed quantification and detection of common diseases., (Published by Elsevier Inc.)

Nanoparticle-based theranostics combines tumor imaging and cancer therapy in one platform, but the synthesis of theranostic agents is impeded by chemical groups on the surface and the size and morphology of the components. Strategies to construct a multifunctional platform for bioimaging and photothermal therapy (PTT) are urgently needed. A new upconversion-magnetic agent (FeCUPs) based on hollow carbon spheres, which is both a photothermal agent and a dual carrier of luminescent and magnetic nanoparticles, provides an effective approach for tumor elimination. Methods: The morphology of FeCUPs was characterized for the construction and size adjustment of the theranostic agent using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy and high angle annular dark field scanning transmission electron microscopy. The distribution of FeCUPs was tracked under in-situ upconversion luminescence (UCL) imaging and magnetic resonance imaging (MRI) in vivo . Photothermal therapy was carried out on tumor-bearing mice, after which the toxicity of PTT was evaluated by a blood biochemistry test and histological section analysis. Results: Stable and uniform loading of luminescent nanocomposites on three-dimensional carbon materials is reported for the first time. Based on the mechanism of synthesis, the size of the hybrid particles was adjusted from micrometers to nanometers. External magnetic field-enhanced photothermal therapy with multi-model imaging was accomplished using FeCUPs. Moreover, no cancer recurrence was found during 14 days of recovery without PTT. Conclusions: Hollow carbon spheres, photothermal agents loaded with upconversion nanoparticles inside and magnetic nanoparticles outside were prepared for photothermal therapy. The aggregation of FeCUPs in tumors by the local magnetic field was verified by MRI and UCL imaging, and PTT was enhanced., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The selective and quantitative detection of cellular H2O2 is essential for understanding its roles in physiology and pathology. A new electrochemical H2O2 biosensor, fabricated by immobilizing horseradish peroxidase onto dendritic mesoporous silica nanoparticles (HRP/DMSNs), is employed for living cell H2O2 detection. Taking advantage of the large pore volume and highly accessible internal surface areas of DMSNs, HRP/DMSNs display higher enzymatic loading, better stability and bioactivity in comparison with HRP on nonporous silica nanoparticles (NSNs). Therefore, a HRP/DMSN modified GCE (HRP/DMSNs/GCE) shows attractive electrochemical performance for sensitive and selective detection of H2O2 in 0.1 M pH 7.0 PBS, with a low Kappm value of 11.48 μM and a low detection limit of 0.11 μM. In addition, HRP/DMSNs/GCE is successfully applied to detect H2O2 released from a PC12 cell triggered by ascorbic acid (AA). The detected H2O2 amount is close to the reported values. The developed biosensor has potential in the dynamic detection of the flux of H2O2 from living cells for further evaluation of oxidative stress in cells.

Photoacoustic responses induced by laser-excited photothermal bubbles (PTBs) in colloidal gold solutions are relevant to the theranostics quality in biomedical applications. Confined to the complexity of nonstationary, multiscale events, and multiphysical parameters of PTBs, systematic studies of the photoacoustic effects remain obscure. Photoacoustic effects mediated by PTB dynamics and a physical mechanism are studied based on a proof-of-principle multimodal platform integrating side-scattering imaging, time-resolved optical response, and acoustic detection. Results show excitation energy, nanoparticle (NP) size, and NP concentration have strong influence on photoacoustic responses. Under the characteristic enhancement regime, the photoacoustic signal amplitude increases linearly with excitation energy and increases quadratically with the NP diameter. As for the effects of the NP concentration (characterized by absorption coefficient), a higher photoacoustic signal amplitude is generally induced by a dense NP distribution. However, with an increase in the NP size, the shielding effect of NP swarm prevents the increase of photoacoustic responses. This study presents experimental evidence of some key physical phenomena governing the PTB-induced photoacoustic signal generation in gold NP suspensions, which may help enrich theranostic approaches in clinical applications by rationalizing operation parameters., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Camptothecin (CPT) is an important topoisomerase I enzyme (Topo I) targeting anti-cancer drug, but its oral administration is limited by poor bioavailability and severe side effects. In this study, a redox sensitive CPT prodrug loaded solid lipid nanoparticles (SLN) system for oral delivery was developed. First of all, CPT-palmitic acid conjugate via a cleavable disulfide bond linker (CPT-SS-PA) was synthesized and encapsulated into SLN. The drug release of SLN was evaluated in neutral environment, simulated gastrointestinal fluid and reductive solution. The results indicated that CPT-SS-PA SLN maintained chemical structural stability in simulated physiological environment but exhibited quick reduction-response release of CPT in the presence of dithiothreitol. Furthermore, in vitro cytotoxicity of CPT-SS-PA SLN was tested against cancer cell lines, and the cellular uptake behavior for oral delivery was checked by confocal laser scanning microscopy (CLSM) using Caco-2 cells model. From the data, CPT-SS-PA SLN revealed high anti-cancer activity and enhanced Caco-2 cell absorption. Finally, the oral bioavailability and intestinal safety of CPT-SS-PA SLN were preliminary evaluated by in vivo pharmacokinetic and histopathological study, respectively. This study demonstrated that CPT-SS-PA SLN could be developed as an effective CPT oral delivery system due to its enhanced oral bioavailability and reduced intestinal side effect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C 16 ), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

Supramolecular construction of a targeted and stimuli-responsive drug delivery system is still a challenging task. Herein, GSH-responsive supramolecular prodrug nanoparticles were constructed by the host-guest complexation between a β-d-galactose-functionalized water-soluble pillar[5]arene (GalP5) and a disulfide bond containing camptothecin prodrug (G). The obtained prodrug nanoparticles were stable under physiological conditions, whereas efficient drug release was triggered in a simulated tumor environment with high GSH concentration. In vitro studies revealed that these prodrug nanoparticles preferentially entered asialoglycoprotein receptor-overexpressing HepG2 cells due to the active targeting effect of galactose units. This active targeting effect resulted in the maximization of anticancer efficacy and reduction of the undesirable side effects to normal cells.

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle's stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method. They were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results revealed that the DBTP nanovesicles have a spherical structure with an average diameter approximately 138.7nm and a negatively charged surface (-33.3±2.5mV). The loading efficiency of Bex is 76wt% after a simple calculation. In vitro degradation of DBTP nanovesicles and the release of Bex were further studied in detail. The results demonstrated that DBTP nanovesicles were stable in neutral environment but degraded in a weakly acidic condition and released parent drug Bex effectively. Cellular uptake was investigated by confocal laser scanning microscope (CLSM) and liquid chromatography-mass spectroscopy (LC-MS). The results demonstrated the successful internalization and intracellular release of DBTP nanovesicles. Furthermore, the cytotoxicity analysis and apoptosis of the nanovesicles showed higher antitumor activities compared with free Bex. In a conclusion, DBTP nanovesicles could be an effective nanoformulation of Bex., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the present study, we developed a novel type of reduction-sensitive nanoparticles (NPs) for docetaxel (DTX) delivery based on cross-linked lipoic acid NPs (LANPs). The physicochemical properties, cellular uptake and in vitro cytotoxicity of DTX loaded LANPs (DTX-LANPs) on A549 cells were investigated. Furthermore, the in vivo distribution and in vivo efficacy of DTX-LANPs was evaluated. The results showed that DTX-LANPs had a particle size of 110 nm and a negative zeta potential of -35 mv with excellent colloidal stability. LANPs efficiently encapsulated DTX with a high drug loading of 4.51% ± 0.49% and showed remarkable reduction-sensitive drug release in vitro. Cellular uptake experiments demonstrated that LANPs significantly increased intracellular DTX uptake by about 10 fold as compared with free DTX. The cytotoxicity of DTX-LANPs showed significantly higher potency in inhibiting A549 cell growth than free DTX, while blank LANPs had a good biocompatibility. In addition, in vivo experiments demonstrated that DTX-LANPs could enhance tumour targeting and anti-tumour efficacy with low systemic toxicity. In conclusion, LANPs may prove to be a potential tumour microenvironment-responsive delivery system for cancer treatment, with the potential for commercialization due to the simple component, controllable synthesis, stability and economy.

Overcoming multidrug resistance is achieved by developing a novel drugdelivery-system paradigm based on azobenzene liposome and phosphatidylcholine-modified upconversion nanoparticle (UCNP) hybrid vesicles for controlled drug release using a nearinfrared (NIR) laser. Upon 980 nm light irradiation, the reversible photoisomerization of the azobenzene derivatives by simultaneous UV and visible light emitted from the UCNPs makes it possible to realize NIR-triggered release of the chemotherapeutic drug doxorubicin., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peptide modification of nanoparticles with high efficiency is critical in determining the properties and bioapplications of nanoparticles, but the methodology remains a challenging task. Here, by using the phosphorylated linear and cyclic peptide with the arginine-glycine-aspartic acid (RGD) targeting motifs as typical examples, the peptides binding efficiency for the inorganic metal compound nanoparticles was increased significantly after the phosphorylation treatment, and the modification allowed for improving the selectivity and signal-to-noise ratio for cancer targeting and reduced the toxicity derived from nonspecific interactions of nanoparticles with cells owing to the higher amount of phosphopeptide binding. In addition, molecular dynamics (MD) simulations of various peptides on inorganic metal compound surfaces revealed that the peptide adsorption on the surface is mainly driven by electrostatic interactions between phosphate oxygen and the polarized interfacial water layer, consistent with the experimental observation of the strong binding propensity of phosphorylated peptides. Significantly, with the RGD phosphopeptide surface modification, these nanoparticles provide a versatile tool for tuning material-cell interactions to achieve the desired level of autophagy and may prove useful for various diagnostic and therapeutic applications.

Treatment of inflammatory diseases represents one of the biggest clinical challenges. RNA interference (RNAi) against TNF-α provides a promising modality toward anti-inflammation therapy, but its therapeutic potential is greatly hampered by the by the lack of efficient siRNA delivery vehicles in vivo. Herein, we report a hybrid nanoparticulate (HNP) system based on a cationic helical polypeptide PPABLG for the efficient delivery of TNF-α siRNA. The helical structure of PPABLG features pore formation on cellular and endosomal membranes to facilitate the direct translocation as well as endosomal escape of TNF-α siRNA in macrophages, representing a unique superiority to a majority of the existing polycation-based gene vectors that experience severe endosomal entrapment and lysosomal degradation. As such, HNPs containing TNF-α siRNA afforded effective systemic TNF-α knockdown following systemic administration at a low dose of 50 μg of siRNA/kg and thus demonstrated a potent anti-inflammatory effect to rescue animals from LPS/d-GalN-induced hepatic sepsis. This study therefore verifies that the bioactive secondary structure of polypeptides significantly dominates the in vivo siRNA delivery efficiency, and the unique properties of PPABLG HNPs render remarkable potentials for anti-inflammation therapies.