Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

Composite Hydrogel for the Targeted Capture and Photothermal Killing of Bacteria toward Facilitating Wound Healing.

Pathogenic infections pose a significant risk to public health and are regarded as one of the most difficult clinical treatment obstacles. A reliable and safe photothermal antibacterial platform is a promising technique for the treatment of bacterial infections. Given the damage that high temperatures cause in normal tissues and cells, a multifunctional hydrogel driven by photothermal energy is created by trapping bacteria to reduce heat transfer loss and conduct low-temperature photothermal sterilization efficiently. The 3-aminobenzene boronic acid (ABA)-modified graphene oxide is combined with carboxymethyl chitosan (CMCS) and cellulose nanocrystalline (CNC) networks to create the ABA-GO/CNC/CMCS composite hydrogel (composite gel). The obtained composite gel displays a uniform three-dimensional network structure, which can be rapidly heated to 48 °C under infrared light irradiation and is beneficial for killing wound infection bacteria and promoting wound healing. The results of animal experiments show that the composite gel significantly reduces inflammation by killing >99.99% of bacteria under near-infrared light irradiation. The result also demonstrates that it increases the granulation tissue thickness and collagen distribution and promotes wound healing. After treatment for 14 days, compared with the remaining 27.73% of the remaining wound area in the control group, the wound area in the composite gel with NIR group is only 0.91%. It significantly accelerates the wound healing process of Staphylococcus aureus infection and shows great potential for clinical application.

Synthesis of Lightweight Renewable Microwave-Absorbing Bio-Polyurethane/Fe3O4 Composite Foam: Structure Analysis and Absorption Mechanism.

Sustainable renewable polymer foam used as a lightweight porous skeleton for microwave absorption is a novel strategy that can effectively solve the problems of the large surface density, high additive amount, and narrow absorbing band of absorbing materials. In this article, novel renewable microwave-absorbing foams were prepared using Sapiumse biferum kernel oil-based polyurethane foam (BPUF) as porous matrix and Fe3O4-nanoparticles as magnetic absorbents. The microstructure and the microwave absorption performance, the structural effects on the properties, and electromagnetic mechanism of the magnetic BPUF (mBPUF) were systematically characterized and analyzed. The results show that the mBPUF displayed a porous hierarchical structure and was multi-interfacial, which provided a skeleton and matching layer for the Fe3O4 nanoparticles. The effective reflection loss (RL ≤ -10 dB) frequency of the mBPUF was from 4.16 GHz to 18 GHz with only 9 wt% content of Fe3O4 nanoparticles at a thickness of 1.5~5 mm. The surface density of the mBPUF coatings was less than 0.5 kg/cm2 at a thickness of 1.8 mm. The lightweight characteristics and broadband absorption were attributed to the porous hierarchical structures and the dielectric combined with the magnetic loss effect. It indicates that the mBPUF is a prospective broadband-absorbing material in the field of lightweight stealth materials.

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.

Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. RESULTS: Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. CONCLUSIONS: The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

Flexible liposomal gel dual-loaded with all-trans retinoic acid and betamethasone for enhanced therapeutic efficiency of psoriasis.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT. RESULTS: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis. CONCLUSIONS: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Tofacitinib citrate-based liposomes for effective treatment of rheumatoid arthritis.

Low drug concentrations at interest sites and unwanted systemic side effects are major obstacles to effective therapy of rheumatoid arthritis (RA). With the aim of improving the efficacy of tofacitinib citrate (TOF), a liposomal system was developed for targeted delivery to inflamed joints, and this approach was validated in a RA rat model. TOF was effectively loaded into the liposomes (entrapment efficiency: 86.5±1.9%; drug loading: 2.3±0.05%) by a pH gradient method, and these molecules featured sustained drug release behaviour over 48 h. In vitro and in vivo studies showed that TOF loaded liposomes (TOFL) could be selectively taken up by inflamed cells and showed improved accumulation in arthritic paws, demonstrating the superior target ability to RA tissues. Moreover, compared to free TOF, TOFL significantly improved the therapeutic efficacy, reduced the inflammatory cytokine expression and lipid peroxidation in synovial cells in the joint tissue of RA rats. Overall, these results indicate that TOFL served as the useful nanocarriers for RA-targeted therapy.

Sialic Acid-Functionalized PEG-PLGA Microspheres Loading Mitochondrial-Targeting-Modified Curcumin for Acute Lung Injury Therapy.

Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.

Highly Stable, Protein-Resistant Surfaces via the Layer-by-Layer Assembly of Poly(sulfobetaine methacrylate) and Tannic Acid.

Zwitterionic materials have received great attention because of the non-fouling property. As a result of the electric neutrality of zwitterionic polymers, their layer-by-layer (LBL) assembly is generally conducted under specific conditions, such as very low pH values or ionic strength. The formed multilayers are unstable at high pH or in a high ionic strength environment. Therefore, the formation of highly stable multilayers of zwitterionic polymers via the LBL assembly process is still challenging. Here, we report the LBL assembly of poly(sulfobetaine methacrylate) (PSBMA) with a polyphenol, tannic acid (TA), for protein-resistant surfaces. The assembly process was monitored by a quartz crystal microbalance (QCM) and variable-angle spectroscopic ellipsometry (VASE), which confirms the formation of thin multilayer films. We found that the (TA/PSBMA)n multilayers are stable over a wide pH range of 4-10 and in saline, such as 1 M NaCl or urea solution. The surface morphology and chemical composition were characterized by specular reflectance Fourier transform infrared spectroscopy (FTIR/SR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Furthermore, (TA/PSBMA)n multilayers show high hydrophilicity, with a water contact angle lower than 15°. A QCM was used to record the dynamic protein adsorption process. Adsorption amounts of bovine serum albumin (BSA), lysozyme (Lys), and hemoglobin (Hgb) on (TA/PSBMA)20 multilayers decreased to 0.42, 52.9, and 37.9 ng/cm(2) from 328, 357, and 509 ng/cm(2) on a bare gold chip surface, respectively. In addition, the protein-resistance property depends upon the outmost layer. This work provides new insights into the LBL assembly of zwitterionic polymers.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

Copper-containing nanoparticles: Mechanism of antimicrobial effect and application in dentistry-a narrative review.

Copper has been used as an antimicrobial agent long time ago. Nowadays, copper-containing nanoparticles (NPs) with antimicrobial properties have been widely used in all aspects of our daily life. Copper-containing NPs may also be incorporated or coated on the surface of dental materials to inhibit oral pathogenic microorganisms. This review aims to detail copper-containing NPs' antimicrobial mechanism, cytotoxic effect and their application in dentistry.

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia.

Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae. After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae. After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.

DNA-Functionalized Liposomes In Vivo Fusion for NIR-II/MRI Guided Pretargeted Ferroptosis Therapy of Metastatic Breast Cancer.

In clinic, metastasis is still the main reason for death for cancer patients. Therefore, it is necessary to track cancer metastases accurately, kill cancer cells effectively, and then improve the prognosis of patients with advanced cancer. Therefore, we designed a liposome-based pretargeted system modified with single-stranded DNA and targeting peptide injected in sequence and then assembled in vivo for multimodality imaging-guided pretargeted synergistic therapy of metastatic breast cancer. The pretargeted system is composed of the first liposome, loaded with near-infrared fluorescence imaging (NIR-II) probe downconversion nanoprobes (DCNP) and magnetic resonance imaging (MRI) contrast agent SPIO (L1/C-Lipo/DS), for primary/metastatic tumor MRI/NIR-II dual-modal imaging, and the second liposome, loaded with glucose oxidase (GOx) and doxorubicin (DOX) (L2/C-Lipo/GD), as the therapeutic component. The SPIO in L1/C-Lipo/DS accumulated in the tumor tissue will provide a necessary iron ion for the therapeutic liposome (L2/C-Lipo/GD) to exert the pretargeted ferroptosis therapy to cancer cells. We demonstrate that the DNA-mediated pretargeting strategy can realize the multimodality imaging-guided synergistically enhanced antitumor effect between the two liposomes. This pretargeted and synergistic in vivo assembly nanomedicine strategy for diagnosis and treatment holds clinical translation potential for cancer management.

Cellulose-derived polyols as high-capacity adsorbents for rapid boron and organic pollutants removal from water.

Excess boron in water could result in a critical hazard to plants and humans. Traditional treatment approaches cannot efficiently remove boron from water, especially during seawater desalination using reverse osmosis technology. Achieving satisfactory adsorption capacity and rate for boron remains an unmet goal for decades. Herein, we report cellulose-derived polyols as high-performance adsorbents that can rapidly remove boron and organic pollutants from water. Cellulose-derived polyols were synthesized from saccharides and cellulose via controlled radical polymerization and click reaction. Remarkably, CA@NMDG can adsorb boron with an astonishing capacity of ~34 mg g-1 in 10 min, which surpasses all those cellulose-based materials reported thus far, meanwhile, much faster than those of commercial adsorption resin. Moreover, cellulose-derived polyols also showed high removal efficiencies (70-98% in several minutes) toward certain organic pollutants, including Congo red and Reactive Blue 19. The water-insoluble characteristic of cellulose-derived polyols is advantageous to be separated from the treated sewage after adsorption for reuse. This work provides a novel insight into the fabrication of safe, fast, and high-capacity cellulose adsorbents for water purification.

Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.

Multifunctional Microspheres Dual-Loaded with Doxorubicin and Sodium Bicarbonate Nanoparticles to Introduce Synergistic Trimodal Interventional Therapy.

Lactic acid in the tumor microenvironment is highly correlated with the prognosis of tumor chemoembolization, but there are limited clinical strategies to deal with it. To improve the efficacy, NaHCO3 nanoparticles are innovatively introduced into drug-loaded microspheres to neutralize lactic acid in the tumor microenvironment. Here we showed that multifunctional ethyl cellulose microspheres dual-loaded with doxorubicin (DOX) and NaHCO3 nanoparticles (DOX/NaHCO3-MS) presented excellent antitumor effects by improving the pH of the tumor microenvironment. The homeostasis of the tumor microenvironment was continuously disturbed due to the sustained release of NaHCO3 nanoparticles, which also led to a significant increase in tumor cell apoptosis (compared with the control and DOX-MS groups). We also showed that the administration of DOX/NaHCO3-MS via the hepatic artery in a rabbit model of VX2 orthotopic liver cancer resulted in optimal antitumor efficacy, and the area of tumor necrosis at the embolization site was significantly increased and the proliferation of tumor cells was significantly weakened. The designed DOX/NaHCO3-MS exhibited strong synergistic antitumor effects of embolization, chemotherapy, and tumor microenvironment improvement. The present microspheres provided a strategy for the enhancement of the chemoembolization of hepatocellular carcinoma, which could also be extended to other clinical embolization treatments for blood-rich solid tumors.

Recent Progress and Future Directions: The Nano-Drug Delivery System for the Treatment of Vitiligo.

Vitiligo is a depigmentation disease that seriously affects the physical health, mental health and quality of life of a patient. Therapeutic aim at control immunoreaction by relieving oxidative stress. Unfortunately, the cuticle barrier function and lack of specific accumulation lead to unsatisfactory therapeutic outcomes and side effects. The introduction and innovation of nanotechnology offers inspiration and clues for the development of new strategies to treat vitiligo. However, not many studies have been done to interrogate how nanotechnology can be used for vitiligo treatment. In this review, we summarize and analyze recent studies involving nano-drug delivery systems for the treatment of vitiligo, with a special emphasis on liposomes, niosomes, nanohydrogel and nanoparticles. These studies made significant progress by either increasing drug loading efficiency or enhancing penetration. Based on these studies, there are three proposed principles for topical nano-drug delivery systems treatment of vitiligo including the promotion of transdermal penetration, enhancement of drug retention and facilitation of melanin regeneration. The presentation of these ideas may provide inspirations for the future development of topical drug delivery systems that will conquer vitiligo.

MR molecular imaging of HCC employing a regulated ferritin gene carried by a modified polycation vector.

Purpose: Early diagnosis is essential for reducing liver cancer mortality, and molecular diagnosis by magnetic resonance imaging (MRI) is an emerging and promising technology. The chief aim of the present work is to use the ferritin gene, modified by the alpha-fetoprotein (AFP) promoter, carried by a highly safe vector, to produce signal contrast on T2-weighted MR imaging as an endogenous contrast agent, and to provide a highly specific target for subsequent therapy. Methods: Polyethyleneimine-ß-cyclodextrin (PEI-ß-CD, PC) was synthesized as a novel vector. The optimal nitrogen/phosphorus ratio (N/P) of the PC/plasmid DNA complex was determined by gel retardation, biophysical properties and transmission electron microscopy morphological analysis. The transfection efficiency was observed under a fluorescence microscope and analyzed by flow cytometry. Cellular iron accumulation caused by ferritin overexpression was verified by Prussian blue staining, and the resulting contrast imaging effect was examined by MRI. Results: The modified cationic polymer PC was much safer than high molecular weight PEI, and could condense plasmid DNA at an N/P ratio of 50 with suitable biophysical properties and a high transfection efficiency. Overexpression of ferritin enriched intracellular iron. The short-term iron imbalance initiated by AFP promoter regulation only occurred in hepatoma cells, resulting in signal contrast on MRI. The specific target TfR was also upregulated during this process. Conclusion: These results illustrate that the regulated ferritin gene carried by PC can be used as an endogenous contrast agent for MRI detection of hepatocellular carcinoma (HCC). This molecular imaging technique may promote safer early diagnosis of HCC, and provide a more highly specific target for future chemotherapy drugs.

A dual deformable liposomal ointment functionalized with retinoic acid and epidermal growth factor for enhanced burn wound healing therapy.

An ointment containing retinoic acid deformable liposomes (TRA DLs) and epidermal growth factor cationic deformable liposomes (EGF CDLs) was prepared for the treatment of deep partial-thickness burns. The characterization tests confirmed both liposomes featured small particle sizes, high drug entrapment efficiencies and sustained drug release behavior. Compared with the free drug, TRA DLs and EGF CDLs exhibited superior skin permeation and remarkably increased drug deposition by 2.9 and 18.8 folds, respectively. Results on HaCaT cells indicated the combined application of two liposomes exerted a synergistic effect and prominently promoted cell proliferation and migration. Application of the dual liposomal ointment on a deep partial-thickness burn model stimulated wound closure (p < 0.001), promoted skin appendage formation and increased collagen production, thus improving healing quality. Finally, it was demonstrated that TRA significantly up-regulated the expression of EGFR and HB-EGF to enhance the therapeutic effect of EGF. Therefore, the dual liposomal ointment is a promising topical therapeutic for burn treatment.

Combinational protective therapy for spinal cord injury medicated by sialic acid-driven and polyethylene glycol based micelles.

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes and loss of neurons, followed by extensive secondary injury process. Treatment of SCI still remains a tremendous challenge clinically. Minocycline could target comprehensive secondary injury via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Polyethylene glycol (PEG), a known sealing agent, is able to seal the damaged cell membranes and reduce calcium influx, thereby exerting neuroprotective capacity. Here, an E-selectin-targeting sialic acid - polyethylene glycol - poly (lactic-co-glycolic acid) (SAPP) copolymer was designed for delivering hydrophobic minocycline to achieve combinational therapy of SCI. The obtained SAPP copolymer could self-assemble into micelles with critical micelle concentration being of 13.40 µg/mL, and effectively encapsulate hydrophobic minocycline. The prepared drug-loaded micelles (SAPPM) displayed sustained drug release over 72 h, which could stop microglia activation and exhibited excellent neuroprotective capacity in vitro. The SAPP micelles were efficiently accumulated in the lesion site of SCI rats via the specific binding between sialic acid and E-selectin. Due to the targeting distribution and combinational effect between PEG and minocycline, SAPPM could obviously reduce the area of lesion cavity, and realize more survival of axons and myelin sheaths from the injury, thus distinctly improving hindlimb functional recovery of SCI rats and conferring superior therapeutic effect in coparison with other groups. Our work presented an effective and safe strategy for SCI targeting therapy. Besides, neuroprotective capacity of PEG deserves further investigation on other central nervous system diseases.