Recent advances in nanomedicines for regulation of macrophages in wound healing

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

Multifunctional and durable graphene-based composite sponge doped with antimonene nanosheets

The development of flexible multifunctional composites is an important topic in the fields of materials engineering, electronics, aerospace and biomedicine. However, there are still major challenges to achieve a variety of functions to meet the requirement for the application. Herein, a flexible multifunctional porous composite is successfully prepared by fabricating both modified graphene and antimonene into a melamine sponge. Compared with the graphene composite sponge, the addition of antimonene improved its electrochemical and sensing performances. The specific capacitance of antimonene/graphene composite sponge was significantly increased, while the capacitance retention rate was 83% under 20,000 charge–discharge cycles. The pressure sensitivity of the prepared flexible multifunctional device assembled was 44% higher than that of the graphene composite sponge. A power supply-integrated sensing system was assembled for monitoring human motion signals. The experimental results show that this system is a promising monitoring device with broad potentials in the fields of biosensing

Neurotoxicity of nanoparticles : insight from studies in zebrafish

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

Photoactivatable nanogenerators of reactive species for cancer therapy

In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O2●), nitric oxide (●NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments

Co-delivery of gemcitabine and Triapine by calcium carbonate nanoparticles against chemoresistant pancreatic cancer

Pancreatic cancer is a malignant disease with high mortality, and its systemic treatment strategy mainly focuses on chemotherapy. Yet, the overall prognosis of pancreatic cancer patients is still extremely poor with a low survival rate. Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of pancreatic cancer. However, GEM chemoresistance remains the major challenge. In this study, we prepared calcium carbonate nanoparticles (CaCO3 NPs) loaded with a nucleotide reductase inhibitor (Triapine) and GEM to suppress the GEM resistance of pancreatic cancer cells (PANC-1/GEM) and solve the problem of poor solubility of Triapine. CaCO3-GEM-Triapine NPs nano-formulations enhanced the therapeutic effect of GEM-based chemotherapy by inhibiting cancer cell proliferation, migration, and resistance to GEM using both 2D PANC-1/GEM cells and 3D tumor spheroids. The study indicated that CaCO3 NPs loaded with GEM and Triapine could provide an effective treatment option to overcome drug resistance in pancreatic cancer

Natural product-based bioactive agents in combination attenuate neuroinflammation in a tri-culture model

Introduction: Neuroinflammation is an important pathological event contributing to the onset and progression of neurodegenerative diseases. The hyperactivation of microglia triggers the release of excessive proinflammatory mediators that lead to the leaky blood-brain barrier and impaired neuronal survival. Andrographolide (AN), baicalein (BA) and 6-shogaol (6-SG) possess anti-neuroinflammatory properties through diverse mechanisms of action. The present study aims to investigate the effects of the pair-combinations of these bioactive compounds in attenuating neuroinflammation. Methods: A tri-culture model with microglial N11 cells, microvascular endothelial MVEC(B3) cells, and neuroblastoma N2A cells was established in a transwell system. AN, BA and 6-SG used alone (25 µM) or in pair-wised combinations (12.5 + 12.5 µM) were subjected to the tri-culture system. Upon the stimulation of lipopolysaccharides (LPS) at 1 μg/mL, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were determined by ELISA assays. Immunofluorescence staining was applied to investigate the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) on N11 cells, expressions of protein zonula occludens-1 (ZO-1) on MVEC cells and phosphorylated tau (p-tau) on N2A cells, respectively. The endothelial barrier permeability of MVEC cells was assessed by the Evans blue dye, and the resistance from the endothelial barrier was measured by transepithelial/endothelial electrical resistance (TEER) value. Neuronal survival of N2A cells was determined by Alamar blue and MTT assays. Results: Combinations of AN-SG and BA-SG synergistically lowered the TNF and IL-6 levels in LPS-induced N11 cells. Remarkably, the combined anti-neuroinflammatory effects of AN-SG and BA-SG remained significantly greater compared to their individual components at the same concentration level. The molecular mechanism of the attenuated neuroinflammation was likely to be mediated by downregulation of NF-κB p65 translocation (p < 0.0001 vs. LPS stimulation) in N11 cells. In the MVEC cells, both ANSG and BA-SG restored TEER values, ZO-1 expression and reduced permeability. Furthermore, AN-SG and BA-SG significantly improved neuronal survival and reduced expressions of p-tau on N2A cells. Discussion: The AN-SG and BA-SG combinations showed greater antineuroinflammatory potential than those used alone in mono- and tri-cultured N11 cells, thereby further protecting endothelial tight junction and neuronal survival. Taken together, AN-SG and BA-SG may provide improved antineuroinflammatory and neuroprotective activities

A facile approach to fabricate highly sensitive, flexible strain sensor based on elastomeric/graphene platelet composite film

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

Biomimetic recombinant of red blood cell membranes for improved photothermal therapy

Background: RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function. Results: In this study, we reported a green technology of “disassembly-reassembly” to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing IR780@rRBC NPs with IR780@RBC NPs and free IR780 as controls. The results demonstrated the superiority of IR780@rRBC NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with IR780@rRBC and free IR780. Conclusions: The reported “disassembly-reassembly” strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles

Docetaxel-loaded M1 macrophage-derived exosomes for a safe and efficient chemoimmunotherapy of breast cancer

The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy

M1 macrophage-derived exosomes loaded with Gemcitabine and Deferasirox against chemoresistant pancreatic cancer

Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer