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Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects the life quality of patients. Topical administration of glucocorticoids is considered to be the most effective anti-inflammatory treatment. However, due to the barrier function of skin, only less than 20% of topical drug molecules could diffuse into the skin. Therefore, it is of great importance to develop an effective strategy to improve AD therapy. In this study, we reported a two-electrode microneedle patch (t-EMNP) composed of a polylactic acid-platinum (PLA-Pt) MN array and polylactic acid-platinum-polypyrrole (PLA-Pt-PPy) MN array for improving the transdermal drug delivery efficacy. The drug loading capability of MNs could be altered by employing different polymerization times and drug concentrations. The drug release rate of MNs could be changed by applying different voltages. We further developed a controlled transdermal drug delivery system (c-TDDS) based on this two-electrode microneedle patch (t-EMNP), exhibiting the remarkable performance of the electricity-triggered drug release profile. The drugs could be released with electrical stimulation, while there was almost no drug release without electrical stimulation. For AD treatment

Microneedles (MNs) have been developed for various applications such as drug delivery, cosmetics, diagnosis, and biosensing. To meet the requirements of MNs used in these areas, numerous materials have been used for the fabrication of MNs. However, MNs will be exposed to skin tissues after piercing the stratum corneum barrier. Thus, it is necessary to ensure that the matrix materials of MNs have the characteristics of low toxicity, good biocompatibility, biodegradability, and sufficient mechanical properties for clinical application. In this review, the matrix materials currently used for preparing MNs are summarized and reviewed in terms of these factors. In addition, MN products used on the market and their applications are summarized in the end. This work may provide some basic information to researchers in the selection of MN matrix materials and in developing new materials.

Background It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects. Materials and methods Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated. Results and discussion The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug -loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control. Conclusion All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.

Photothermal therapy (PTT) is a treatment combining laser irradiation and a photothermal transduction agent (PTA) to generate hyperthermia, which is used to efficiently and effectively treat cancer and prevent bacteria-induced infectious diseases. MoS2, an increasingly used two-dimensional transition metal dichalcogenide, which shows high absorbance in the near infrared (NIR) laser region, has been extensively utilized as a novel PTA in biomedical applications. The use of MoS2 as an advanced photoabsorbing agent has introduced a more efficient cancer therapy and improved antibacterial efficacy. In this review, we firstly summarize the recent advances in the MoS2-based platform for PTT in cancer and bacteria-induced infectious diseases treatments. We then discuss that the combination of MoS2-based PTT and other biomedical methods along with multimodality imaging, such as chemotherapy, photodynamic therapy (PDT) and immunotherapy, might be a promising strategy for cancer treatment. Furthermore, a new concept is proposed wherein MoS2-based PTT and combined therapies based on this could be more effective for the treatment of various bacteria-induced infectious diseases. Finally, research progress, challenges, and perspectives for the future development of this MoS2-based platform in cancer and bacteria-induced infectious disease treatments are discussed and concluded. Collectively, we think that MoS2-based PTT with high therapeutic efficacy and minimal side-effects could be potentially applied in clinical settings to improve cancer and infectious disease treatments.

Diabetes is one of the most serious chronic diseases today. Patients with diabetes need frequent insulin injections or blood sampling to monitor blood glucose levels. The microneedles are a painless transdermal drug delivery system, which has great advantages in achieving self-management. There have been a lot of researches on microneedles used in diabetes treatment. Microneedle-based treatment of diabetes has also changed from a simple and reliable system to a complex and efficient system. This review introduces microfluidic, glucose response, and other contents based on microneedles, and some challenges in the development of microneedles.

Nanomaterial drug delivery systems have become one of the most important targeted therapy technologies. Although great efforts have been made to study the self-assembled mesoscopic structure of nanoparticles and understand drug loading and release mechanisms, the interaction between nanoparticles and cell membranes has not yet been clearly studied. Moreover, the research of experimental methods in this field has been greatly restricted due to its special time-space scale, so it is necessary to apply computer simulations to visualize the cell internalization of the nanoparticle. This review covers modelling methods and the current status and viewpoints of research on the influencing factors of the nanoparticle-biomembrane interaction mechanism. In particular, we discussed in detail the positive and negative effects of various nanoparticle properties. This article may assist researchers in rationally optimize the nanoparticle structure to improve therapeutic efficiency.

Background The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance. Methods In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pK b value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility. Results The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX. Conclusion All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.

Dysregulated vascular inflammation is the underlying of acute lung inflammation/injury (ALI). Bacterial infections and trauma cause ALI that may rapidly lead to acute respiratory distress syndrome (ARDS). There are no pharmacological therapies available to patients with ALI/ARDS, partially as drugs cannot specifically target the lungs. Herein, we developed a stimuli-responsive nanoparticle to target inflammatory lungs for ALI therapies. The nanoparticle is comprised of a sharp acid-sensitive segment poly(β-amino esters) (PAE) as a core for drug loading and controlled release, and a polyethylene glycol (PEG)-biotin on the particle surface available for bioconjugation enabling lung targeting and extended circulation. The studies on dissipative particle dynamics (DPD) simulation and characteristics of nanoparticles (NPs) suggest that anti-ICAM-1 antibodies can be coated to the particle surface and this coating is required to enhance lung targeting of NPs. A model drug of anti-inflammatory agent TPCA-1 is encapsulated in NPs with high drug loading content at 24 % (w/w). In the mouse ALI model, our TPCA-1-loaded NPs coated with anti-ICAM-1 can target inflamed lungs after intravenous injection, followed by drug release triggered by acid environment, thus mitigating lung inflammation and injury. Our studies reveal the rational design of nanotherapeutics for improved therapy of ALI and it may be applied to treating a wide range of vascular inflammation.

Molybdenum disulfide (MoS2), a transition metal dichalcogenide material, possesses great potential in biomedical applications such as chemical/biological sensing, drug/gene delivery, bioimaging, phototherapy, and so on. In particular, monolayer MoS2 has more extensive applications because of its superior physical and chemical properties; for example, it has an ultra-high surface area, is easily modified, and has high biodegradability. It is important to prepare advanced monolayer MoS2 with enhanced energy exchange efficiency (EEE) for the development of MoS2-based nanodevices and therapeutic strategies. In this work, a monolayer MoS2 film was first synthesized through a chemical vapor deposition method, and the surface of MoS2 was further modified via a baking process to develop p-type doping of monolayer MoS2 with high EEE, followed by confirmation by X-ray photoelectron spectroscopy and Raman spectroscopy analysis. The morphology, surface roughness, and layer thickness of monolayer MoS2 before and after baking were thoroughly investigated using atomic force microscopy. The results showed that the surface roughness and layer thickness of monolayer MoS2 modified by baking were obviously increased in comparison with MoS2 without baking, indicating that the surface topography of the monolayer MoS2 film was obviously influenced. Moreover, a photoluminescence spectrum study revealed that p-type doping of monolayer MoS2 displayed much greater photoluminescence ability, which was taken as evidence of higher photothermal conversion efficiency. This study not only developed a novel MoS2 with high EEE for future biomedical applications but also demonstrated that a baking process is a promising way to modify the surface of monolayer MoS2.

Photothermal therapy (PTT) is a treatment combining laser irradiation and a photothermal transduction agent (PTA) to generate hyperthermia, which is used to efficiently and effectively treat cancer and prevent bacteria-induced infectious diseases. MoS2, an increasingly used two-dimensional transition metal dichalcogenide, which shows high absorbance in the near infrared (NIR) laser region, has been extensively utilized as a novel PTA in biomedical applications. The use of MoS2 as an advanced photoabsorbing agent has introduced a more efficient cancer therapy and improved antibacterial efficacy. In this review, we firstly summarize the recent advances in the MoS2-based platform for PTT in cancer and bacteria-induced infectious diseases treatments. We then discuss that the combination of MoS2-based PTT and other biomedical methods along with multimodality imaging, such as chemotherapy, photodynamic therapy (PDT) and immunotherapy, might be a promising strategy for cancer treatment. Furthermore, a new concept is proposed wherein MoS2-based PTT and combined therapies based on this could be more effective for the treatment of various bacteria-induced infectious diseases. Finally, research progress, challenges, and perspectives for the future development of this MoS2-based platform in cancer and bacteria-induced infectious disease treatments are discussed and concluded. Collectively, we think that MoS2-based PTT with high therapeutic efficacy and minimal side-effects could be potentially applied in clinical settings to improve cancer and infectious disease treatments.

In recent years, titanium dioxide (TiO2), one of the most vital and classical metal oxides, has been thoroughly investigated and extensively used in many fields of science and technology owing to its outstanding photo-activity. TiO2-based nanosystems become the potential candidate which has been widely utilized in cancer therapy and antimicrobial field because of the high photo-therapeutic activity. In this review, the recent advances in TiO2-based nanosystems for cancer therapy, including photodynamic therapy (PDT), photothermal therapy (PTT) and combination therapy with other strategies, are summarized. The photo-therapies of TiO2-based nanosystems could be promising alternative strategy for traditional cancer therapies due to the deeper penetration depth and the absence of phototoxicity in clinic. Meanwhile, the frontiers in TiO2-based nanosystems for bacteria-induced infectious diseases management are introduced and summarized here. This potential therapy could efficiently and effectively eliminate the bacteria, manage the infection, and avoid the microbial drug-resistance. Finally, the challenges for the future development of TiO2-based nanosystems in biomedical applications are concluded and discussed. Collectively, we think that TiO2-based nanosystems could be potentially applied in clinical fields to promote the improvement of cancer and infections treatments.

The development of intelligent drug delivery system that can efficiently deliver drug to targeted site and release the cargo in a controlled manner is of great significance for cancer chemotherapy. In the present study, dual redox/pH-sensitive amphiphilic copolymer, cholesterol modified poly (β-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-g-Chol), is successfully synthesized via Michael-type step polymerization using disulfide linkage-containing PEG segment. PEGylated lipid is introduced to fabricate the doxorubicin (DOX)-loaded hybrid polymer-lipid nanoparticles (NPs) with (DOX-HDPLNPs) or without (DOX-HPLNPs) disulfides to receive stable NPs with enhanced loading capacity and improved cellular uptake ability as well as serum stability. The HDPLNPs show not only pH-sensitivity because of poly(β-amino esters) (PAE) residues in main chain but also the redox-responsivity due to the disulfides on the side chains with PEG segments. As expected, the DOX-HDPLNPs exhibited the extended blood circulation time and higher serum stability in normal physiological environment, but once deposited in the tumor microenvironment (e.g. low pH value and high GSH concentration), they underwent a dramatic size transition and charge reversal. These features not only can facilitate the NPs accumulation through the enhanced permeability and retention (EPR) effect and endocytosis by tumor cells but also realize the drug controlled release and more efficient tumor inhibition. The in vitro and in vivo results demonstrate that the DOX-HDPLNPs possess the highest therapeutic efficacy with high cellular uptake and negligible cytotoxicity compared to the controls and free drug. Therefore, the HDPLNPs have good potential as smart delivery platforms for hydrophobic anticancer drug delivery due to high uptake by tumor cells and redox/pH-triggered drug release.

Dissolving microneedles (DMNs) prepared from soluble polymers has been being widely investigated as a safe and effective transdermal delivery system for drug and vaccine. Limited by the materials, the air humidity would probably affect the mechanical property of DMNs, which is essential for the effective needle insertions and drug delivery. In this study, four kinds DMNs prepared by polyvinyl alcohol, sodium hyaluronate (HA), chitosan and gelatin are studied on the mechanical strength and insertion ability under varying humidity conditions. Based on these investigations, we hope to provide the effective time of DMNs to ensure a successful insertion and drug delivery.

A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)-g-cholesterol)-b-poly(ethylene glycol)-b-(poly(β-amino esters)-g-cholesterol) ((PAE-g-Chol)-b-PEG-b-(PAE-g-Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 μg/mL, 12.6 μg/mL, 17.4 μg/mL, and 26.6 μg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The pKb of the polymer was confirmed to be approximately 6.5 by the acid-base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20%) and entrapment efficiency (60%) using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the doxorubicin-loaded system showed high toxicity for HepG2 cells as free drugs. All the results proved that the pH-sensitive triblock polymer brush and its self-assembled micelle might be a potential delivery carrier for anticancer drugs with sustained release.

Co-micellization of the diblock polymers poly(ethylene glycol) methyl ether-b-poly(N,N-diethylaminoethyl methacrylate) (MPEG–PDEAEMA) and poly(ethylene glycol) methyl ether-b-polycaprolactone (MPEG–PCL) was carried out to avoid the complicated synthetic steps of a single polymer and enhance the drug loading contents as well as the pH-responsive drug release performances of the polymers. The molecular weight and molecular structure of MPEG–PDEAEMA and MPEG–PCL were measured and confirmed by gel permeation chromatography (GPC) and 1H NMR. With the mass ratio of MPEG–PCL and MPEG–PDEAEMA set at 1 : 3, all three mixed micelles, MIX1 (MPEG–PCL40 and MPEG–PDEAEMA20), MIX2 (MPEG–PCL60 and MPEG–PDEAEMA35), and MIX3 (MPEG–PCL80 and MPEG–PDEAEMA50), showed good stability and excellent pH-responsive performances according to their critical micellar concentrations (CMC), particle sizes, and zeta potentials. The doxorubicin (DOX) loading content (LC) and entrapment efficiency (EE) of the micelles were 26.79% and 63.19% (MIX1), 22.81% and 59.03% (MIX2), and 21.46% and 54.65% (MIX3), respectively. As the PDEAEMA/PCL content increased, the drug loading content decreased, which was further confirmed by dissipative particle dynamics (DPD) simulations. The results indicate that the mixed micelles developed in this study might have some advantages in improving the drug loading capacity of the polymers. The drug release profiles demonstrate that the mixed micelles have excellent ability for the controlled release of DOX, suggesting great potential for application of the micellar systems in drug delivery, especially in the area of pH-targeted tumor treatment.

Nanoparticles target inflammatory neutrophils to deliver doxorubicin for neutrophil apoptosis in resolution of inflammation., Human neutrophils are the most abundant circulating leukocytes and contribute to acute and chronic inflammatory disorders. Neutrophil apoptosis is programed cell death to maintain immune homeostasis, but inflammatory responses to infections or tissue injury disrupt neutrophil death program, leading to many diseases. Precise control of neutrophil apoptosis may resolve inflammation to return immune homeostasis. Here, we report a method in which doxorubicin (DOX)–conjugated protein nanoparticles (NPs) can in situ selectively target inflammatory neutrophils for intracellular delivery of DOX that induces neutrophil apoptosis. We showed that neutrophil uptake of NPs required their activation and was highly selective. DOX release was triggered by acidic environments in neutrophils, subsequently inhibiting neutrophil transmigration and inflammatory responses. In two disease models, DOX-conjugated NPs notably increased mouse survival in sepsis and prevented brain damage in cerebral ischemia/reperfusion, but the NPs did not suppress systemic immunity. Our studies offer a promising strategy to treat inflammatory diseases.

It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(aminoethyl methacrylate) (poly(MMA-co-MAA)-b-PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA-b-PMAA-b-PAEMA) and block copolymer (poly(MMA-co-MAA)-b-PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH &lt, pKa and anomalous at pH &gt, pKa which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA30-co-MAA33)-b-PAEMA38 with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.

Bacterial infections cause a wide range of host immune disorders, resulting in local and systemic tissue damage. Antibiotics are pharmacological interventions for treating bacterial infections, but increased antimicrobial resistance and the delayed development of new antibiotics have led to a major global health threat, the so-called "superbugs". Bacterial infections consist of two processes: pathogen invasion and host immune responses. Developing nanotherapeutics to target these two pathways may be effective for eliminating bacteria and restoring host homeostasis, thus possibly finding new treatments for bacterial infections. This review offers new approaches for developing nanotherapeutics based on the pathogenesis of infectious diseases. We have discussed how nanoparticles target infectious microenvironments (IMEs) and how they target phagocytes to deliver antibiotics to eliminate intracellular pathogens. We also review a new concept-host-directed therapy for bacterial infections, such as targeting immune cells for the delivery of anti-inflammatory agents and vaccine developments using bacterial membrane-derived nanovesicles. This review demonstrates the translational potential of nanomedicine for improving infectious disease treatments.

The development of intelligent oral drug delivery carrier aiming at efficiently bring insulin to intestine is of great significance for diabetes mellitus therapy. In the present study, a series of amphiphilic pH-sensitive block copolymer poly(methyl methacrylate-co-methacrylicacid)-b-poly(2-amino ethyl methacrylate) [P(MMA-co-MAA)-b-PAEMA] was synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and further self-assembled into pH-responsive cationic polymeric micelles (PCPMs) for oral insulin delivery. The structure and molecular weight were confirmed by proton nuclear magnetic resonance (1H-NMR), Fourier transforming infrared spectrum (FT-IR) and gel permeation chromatography (GPC), respectively. The critical micelle concentration (CMC) values of these copolymers were measured by fluorescent probe method at pH 1.2 (8–15 μg/mL) and pH 7.4 (22–42 μg/mL), respectively, demonstrating high stability at acidic environment. A decrease in the particle size of PCPMs was associated with an increased pH at beginning, which reached around 200 nm at neutral pH, while the particle size increased obviously with pH increase, indicating the pH-sensitivity of PCPMs. The insulin was entrapped into the core of PCPMs (Ins-loaded PCPMs) with high loading efficiency via diafiltration method. The in vitro experiments show Ins-loaded PCPMs have low toxicity and exhibit pH-triggered release profile with remitted initial burst release. The results indicate that the PCPMs self-assembled from P(MMA-co-MAA)-b-PAEMA may be potential carriers for efficient oral delivery of insulin with controlled release property.

Photodynamic therapy (PDT) is a treatment by combining light and a photosensitizer to generate reactive oxygen species (ROS) for cellular damage, and is used to treat cancer and infectious diseases. In this review, we focus on recent advances in design of new photosensitizers for increased production of ROS and in genetic engineering of biological photosensitizers to study cellular signaling pathways. A new concept has been proposed that PDT-induced acute inflammation can mediate neutrophil infiltration to deliver therapeutics in deep tumor tissues. Combination of PDT and immunotherapies (neutrophil-mediated therapeutic delivery) has shown the promising translation of PDT for cancer therapies. Furthermore, a new area in PDT is to treat bacterial infections to overcome the antimicrobial resistance. Finally, we have discussed the new directions of PDT for therapies of cancer and infectious diseases. In summary, we believe that rational design and innovations in nanomaterials may have a great impact on translation of PDT in cancer and infectious diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Ischemic stroke is an acute and severe neurological disease, resulting in disability and death. Reperfusion to an ischemic brain is a means to reverse brain damage after stroke; however, this causes secondary tissue damage induced by inflammation responses, called ischemia/reperfusion (I/R) injury. Adhesion of neutrophils to endothelial cells underlies the initiation of inflammation in I/R. Inspired by this interaction, we report a drug delivery system comprised of neutrophil membrane-derived nanovesicles loaded with Resolvin D2 (RvD2) that can enhance resolution of inflammation, thus protecting brain damage during ischemic stroke. In the study, the middle cerebral artery occlusion (MCAO) mouse model was developed to mimic ischemic stroke. Using intravital microscopy of a live mouse brain, we visualized the binding of nanovesicles to inflamed brain vasculature for delivery of therapeutics to ischemic stroke lesions in real-time. We also observed that RvD2-loaded nanovesicles dramatically decreased inflammation in ischemic stroke and improved mouse neurological functions. Our study provides a strategy to inhibit neuroinflammation using neutrophil-derived nanovesicles for ischemic stroke therapy.

The compatibility of an amphiphilic pH-sensitive polymer (docosahexaenoic acid–histidine–lysine, DHA–HisXLys10) and hydrophobic drug (doxorubicin, DOX) was investigated using multiscale simulations at different pH conditions, including Blends and dissipative particle dynamics simulations. Some important elements obtained from the computer simulations were analyzed, such as Flory–Huggins interaction parameters, binding energy distributions, phase diagrams and radius distribution function. In conclusion, the pH values and the number of pH-sensitive segments (histidine) significantly influence the compatibility of DHA–HisXLys10 and DOX, resulting in different drug loading capacity and system structural stability. According to the simulation results, the compatibility of the systems at pH > 6.0 is better than that at pH 6.0. Using DPD simulation, the compatibility of DHA–HisXLys10 (X = 10 or 15) and DOX is optimal when the pH is higher than 6.0, which falls in line with the results obtained from Blends simulation. Overall, when the number of histidine residues is 10 or 15 and the pH is larger than 6.0, DOX and DHA–HisXLys10 have better compatibility. So it is obvious that polymeric micelles self-assembled from DHA–His10Lys10/DHA–His15Lys10 as an ideal drug carrier have higher drug-loading capacity and more excellent stability. This work has demonstrated that multiscale simulations could be a powerful method to investigate the compatibility between polymers and drugs.

Sepsis is a life-threatening disease resulted from a dysregulated host immune response to bacterial infections, continuing to cause high morbidity and mortality worldwide. Despite discoveries of many potential therapeutic targets, effective treatments of sepsis are lacking. Here, a strategy is reported to target infectious microenvironments (IMEs) via bioresponsive nanoparticles that simultaneously eliminate bacteria and alleviate the host inflammation response, thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to pH and bacterial enzymes to self-assemble into a micelle loaded with both an antibiotic (ciprofloxacin) and an anti-inflammatory agent ((2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide). In addition, the nanoparticle is conjugated with intercellular adhesion molecule-1 antibodies to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to deliver therapeutics in on-demand manners is demonstrated using an acute lung bacterial infection mouse model. In the sepsis mouse model induced by peritonitis at a lethal dose of bacterial invasion, it is shown that concurrently targeting pathogens and excessive inflammation pathways is valuable to manage the sepsis. The study illustrates not only the development of a new delivery system but also the mechanism-based therapy of nanomedicine for infectious diseases.

White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a central role in acute inflammation induced by pathogens. Adhesion to vasculature and tissue infiltration of neutrophils are key processes in acute inflammation. Many inflammatory/autoimmune disorders and cancer therapies have been found to be involved in activation and tissue infiltration of neutrophils. A promising strategy to develop novel targeted drug delivery systems is the targeting and exploitation of activated neutrophils. Herein, a new drug delivery platform based on neutrophils is reviewed. There are two types of drug delivery systems: neutrophils as carriers and neutrophil-membrane-derived nanovesicles. It is discussed how nanoparticles hijack neutrophils in vivo to deliver therapeutics across blood vessel barriers and how neutrophil-membrane-derived nanovesicles target inflamed vasculature. Finally, the potential applications of neutrophil-based drug delivery systems in treating inflammation and cancers are presented.

In this work, the formation of polymeric micelles as drug delivery vehicles in an aqueous environment is investigated by dissipative particle dynamics (DPD) simulations. Doxorubicin (DOX) is selected as the model drug, whereas docosahexaenoic acid (DHA) conjugated His10Lys10 (DHA-His10Lys10) as the drug carrier. It is shown from DPD simulation that drug molecules and DHA-His10Lys10 molecules could aggregate and form micelles under a defined composition recipe; drug molecules are homogeneously distributed inside the carrier matrix, on whose surface the stabilizer lysine segments are absorbed. Under different compositions of drug and water, aggregate morphologies of polymeric micelles are observed as spherical, columnar, and lamellar structures. We finally proposed the formation mechanism of drug loaded polymeric micelles and apply it in practice by analyzing the simulated phenomena. All the results can effectively guide the experimental preparation of drug delivery system with desired properties or explore a novel polymeric micelle with high performance.

The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self-assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties.

A mesoporous molybdenum disulfide/carbon (MoS 2 /C) composite with flower-like morphology resulting from the decoration of carbon by MoS 2 interlaced nanosheets was synthesized by a facile hydrothermal route, and utilized for the electrode material of supercapacitor. The morphologies and structures of materials were characterized by field emission scanning electron microscopy, X-ray diffraction, Raman spectrum and N 2 adsorption–desorption isotherm. Electrochemical properties of materials were evaluated by cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy tests of two-electrode supercapacitors. The results indicate that the complex of carbon and MoS 2 can increase the electrical conductivity and can get thinner MoS 2 nanosheets leading to the increment of specific surface area, which result in the improvement in the electrochemical performances of material. The specific capacitance of MoS 2 /C composite reaches 201.4 F g −1 at a current density of 0.2 A g −1 in a two-electrode supercapacitor, which is higher than those of pure MoS 2 and carbon. Additionally, the MoS 2 /C-based supercapacitor exhibits high rate capability and long cyclic durability.

The development of intelligent drug delivery system that can efficiently deliver doxorubicin (DOX) to tumor site with controlled drug release performance and enhanced therapeutic efficacy is of great significance for cancer chemotherapy. In this report, a nano-prodrug system was prepared successfully by conjugating DOX to pH-sensitive amphiphilic diblock copolymer poly (ethylene glycol) methyl ether‑b‑poly (β‑amino esters) through acid-labile cis‑aconityl moiety (mPEG-b-PAE-cis-DOX). The resultant complex copolymer-drug was able to self-assemble into polymeric micelles (PMs) in an aqueous solution at low concentration, and the critical micelle concentration (CMC) was 3.6 mg/L which was increased as decrease of pH value. H-nuclear magnetic resonance (1H NMR), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), transition electron microscopy (TEM), and classic acid-base titration were combined to confirm and characterize the chemical structure of the copolymer/drug conjugates and the physicochemical properties of the prodrug system. The DOX loading capacity, drug delivery and therapeutic efficacy of the conjugates were evaluated in vitro and in vivo. Notably, the antitumor experiments in tumor-bearing mice demonstrated that the pH-responsive nano-prodrug system effectively enhanced the therapeutic efficacy in comparison to free drug. All above results suggested that pH-responsive prodrug system has the potential to be effective carrier for the DOX delivery and pH-triggered controlled release.

The sequence-defined polycationic polymers with or without Cys-Arg-Cys motifs conjugated with targeting and shielding segments were synthesized as siRNA carriers via native chemical ligation (NCL) reaction. After purification, the structures and physicochemical characteristics were determined by a variety of experimental techniques. The particle size of siRNA/CRC-polymer polyplex was much smaller than that of polyplex without CRC motifs. The buffer capacity and siRNA binding ability of CRC motifs modified polymers were significantly improved, resulting from the twin disulfides and hexatomic ring formulation. The critical micelle concentrations of the polymers were10mg/L, indicating formation of polymeric micelles and sufficient stability of the system. The CRC motifs modified polymers with folate targeted ligands exhibited a strongly enhanced cellular uptake than the negative control and the unmodified analogues. The results of gene transfection showed that the folate-PEG-ligated polymer modified with CRC motifs had much better gene transfection compared to the alanine-ended control and other analogues. Furthermore, they showed barely cytotoxicity. By the way, there was no distinctly improvement for pDNA transfection. All above results suggested that folate-PEG-ligated polymers modified with CRC motifs and their self-assembly polymeric micelles could be promising non-viral siRNA carriers.

The anti-creep capability of metallic foams is important to structural applications at elevated temperatures. Currently, available creep models for opened-cell foam materials are usually derived by...

Native chemical ligation (NCL) was established for the conversion of sequence-defined oligomers of different topologies into targeted and PEG shielded pDNA and siRNA carriers. From an existing library of non-targeted oligoethanamino amides, six oligomers containing N-terminal cysteines were selected as cationic cores, to which monodisperse polyethylene glycol (PEG) containing terminal folic acid as targeting ligand (or terminal alanine as targeting negative control ligand) were attached by NCL. Ligated conjugates plus controls (in sum 18 oligomers) were evaluated for pDNA or siRNA gene delivery. Biophysical characteristics including nucleic acid binding in the absence or presence of serum, as well as biological activities in cellular uptake and gene transfer (or gene silencing, respectively) were determined. In most cases, the folic acid-PEG-ligated oligomers displayed a strongly improved cellular binding, uptake and gene transfer into receptor-positive KB cells as compared to the alanine-PEG controls. Changing the topological structures by increasing the number of cationic arms, adding tyrosine trimers as polyplex stabilizing domains, or histidines facilitating endosomal escape resulted in beneficial gene transfer characteristics. The screen revealed different requirements for pDNA and siRNA delivery. A folate-PEG ligated histidinylated four-arm oligomer was most effective for pDNA delivery but inactive for siRNA, whereas a folate-PEG-ligated three-arm oligomer with tyrosine trimer modifications was most effective in siRNA mediated gene silencing. The results demonstrate the site-selective NCL reaction as powerful method to modify existing oligomers. Thus multifunctional targeted carriers can be obtained with ease and used to identify lead structures for subsequent in vivo delivery.