Thermoresponsive Gels with Embedded Starch Microspheres for Optimized Antibacterial and Hemostatic Properties.

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy.

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Hydroxyl-rich branched polycations for nucleic acid delivery.

Recently, nucleic acid delivery has become an amazing route for the treatment of various malignant diseases, and polycationic vectors are attracting more and more attention among gene vectors. However, conventional polycationic vectors still face many obstacles in nucleic acid delivery, such as significant cytotoxicity, high protein absorption behavior, and unsatisfactory blood compatibility caused by a high positive charge density. To solve these problems, the fabrication of hydroxyl-rich branched polycationic vectors has been proposed. For the synthesis of hydroxyl-rich branched polycations, a one-pot method is considered as the preferred method due to its simple preparation process. In this review, typical one-pot methods for fabricating hydroxyl-rich polycations are presented. In particular, amine-epoxide ring-opening polymerization as a novel approach is mainly introduced. In addition, various therapeutic scenarios of hydroxyl-rich branched polycations via one-pot fabrication are also generalized. We believe that this review will motivate the optimized design of hydroxyl-rich branched polycations for potential nucleic acid delivery and their bio-applications.

Genetically light-enhanced immunotherapy mediated by a fluorinated reduction-sensitive delivery system.

The lack of safe and efficient therapeutic agent delivery platforms restricts combined therapy's effect, and combined cancer therapy's multi-component delivery effect needs improvement. The novel gene delivery system SS-HPT-F/pMIP-3ß-KR was proposed to construct fluorine-containing degradable cationic polymers SS-HPT-F by a mild and simple amino-epoxy ring-opening reaction. By modifying the fluorinated alkyl chain, the delivery efficiency of the plasmid was greatly improved, and the cytoplasmic transport of biomolecules was completed. At the same time, a combination plasmid (MIP-3ß-KillerRed) was innovatively designed for the independent expression of immune and photodynamic proteins. Which was efficiently transported to the tumor site by SS-HPT-F. The MIP-3ß is expressed as an immune chemokine realize the immune mobilization behavior. The photosensitive protein KillerRed expressed in the tumor killed cancer cells under irradiation and released the exocrine immune factor MIP-3ß. The immunogenic cell death (ICD) produced by photodynamic therapy (PDT) also induced the immune response of the organism. The synergistic effect of PDT and MIP-3ß mobilized the immune properties of the organism, providing light-enhanced immune combination therapy against malignant tumors. Therefore, in subcutaneous tumor-bearing and metastatic animal models, the carrier tumor growth and mobilize organism produce an immune response without systemic toxicity. This work reports the first efficient gene delivery system that achieves light-enhanced immunotherapy.

Controllable Star Cationic Poly(Disulfide)s Achieve Genetically Cascade Catalytic Therapy by Delivering Bifunctional Fusion Plasmids.

The absence of effective delivery vectors and suitable multifunctional plasmids limits cancer gene therapy development. The star cationic poly(disulfide)s with ß-cyclodextrin cores (termed ß-CD-g-PSSn ) for caveolae-mediated endocytosis are designed and prepared via mild and controllable disulfide exchange polymerization for high-efficacy cancer therapy. Then, ß-CD-g-PSSn /pDNA complexes are transported to the Golgi apparatus and endoplasmic reticulum. Disulfides in ß-CD-g-PSSn vectors are degraded by glutathione in tumor cells, which not only promotes intracellular pDNA release but also reduces in vitro and in vivo toxicity. One bifunctional fusion plasmid pCATKR, which expresses catalase (CAT) fused to KillerRed (KR) (CATKR) in the same target cell, is also proposed for genetically cascade catalytic therapy. When compared with pCAT-KR (plasmid expressing CAT and KR separately in the same cell), delivered pCATKR decomposes hydrogen peroxide, alleviates tumor hypoxia more effectively, generates stronger reactive oxygen species (ROS) capabilities under moderate irradiation, and leads to robust antitumor cascade photodynamic effects. These impressive results are attributed to fusion protein design, which shortens the distance between CAT and KR catalytic centers and leads to improved ROS production efficiency. This work provides a promising strategy by delivering a catalytic cascade functional plasmid via a high-performance vector with biodegradable and caveolae-mediated endocytosis characteristics.

Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy.

The biochemical indicators of tumor microenvironment (TME) that are different from normal tissues provide the possibility for constructing intelligent drug delivery systems (DDSs). Polysaccharides with good biocompatibility, biodegradability, and unique biological properties are ideal materials for constructing DDSs. Nanogels, micelles, organic-inorganic nanocomposites, hydrogels, and microneedles (MNs) are common polysaccharide-based DDSs. Polysaccharide-based DDSs enable precise control of drug delivery and release processes by incorporating TME-specific biochemical indicators. The classification and design strategies of polysaccharide-based TME-responsive DDSs are comprehensively reviewed. The advantages and challenges of current polysaccharide-based DDSs are summarized and the future directions of development are foreseen. The polysaccharide-based TME-responsive DDSs are expected to provide new strategies and solutions for cancer therapy and make important contributions to the realization of precision medicine.

Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

Melanin-Based Immunoregulatory Nanohybrids Enhance Antitumor Immune Responses in Breast Cancer Mouse Model.

Natural melanin nanoparticles (MNPs) have demonstrated a potential for eliciting antitumor immune responses through inducing immunogenic cell death (ICD); however, the tumor microenvironment (TME) has been shown to inhibit T cell-mediated antitumor immunity. To address this challenge, we designed TME-responsive biodegradable melanin/MnOx nanohybrids via a biomineralization process. Under near-infrared (NIR) light irradiation, the photothermal property of melanin/MnOx nanohybrids triggers ICD and release of tumor-associated antigens (TAAs), while Mn2+ and TAAs induce dendritic cell (DC) maturation to provoke immune responses. Furthermore, the immunoregulatory properties of the nanohybrids themselves are exploited to reshape immunosuppressive TME and downregulate PD-L1 through alleviation of the hypoxic and acidic TME. Although MNPs demonstrate higher photothermal killing efficiency than the nanohybrids in vitro due to their superior photothermal effect, the melanin/MnOx nanohybrids exhibit significantly enhanced antitumor and antimetastatic effects in vivo, benefiting from their ability to reverse immunosuppression and induce DC maturation. Transcriptomics analysis confirmed the successful activation of immune responses. This work presents a promising approach for immunomodulation-enhanced cancer therapy through the intrinsic properties of melanin/MnOx nanohybrids.

Mannose-functionalized star polycation mediated CRISPR/Cas9 delivery for lung cancer therapy.

The survivin gene, highly expressed in most cancer cells, is closely associated with inhibiting apoptosis. Therefore, gene editing for the survivin gene has great potential in tumor therapy. However, it is difficult for plasmid DNA (pDNA) to be taken up directly by cells, and thus the construction of gene vectors is a key step for successful gene editing. Ethanolamine-functionalized polyglycidyl methacrylate (PGEA) has been proved to facilitate the transfection of pDNA into cells in both in vivo and in vitro experiments. However, PGEA does not specifically recognize tumor cells. Some tumor cells express more mannose receptor (MR) than healthy cells. To achieve efficient target and transfection, we designed mannose-functionalized four-arm PGEA cationic polymers (P(GEA-co-ManMA), GM) with different molecular weights. GM was combined with pCas9-survivin. The mannose unit of GM/pCas9-survivin was identified by MR to selectively enter lung cancer cells. In vitro experiments showed that GM not only had excellent biocompatibility, gene transfection performance, and targeted ability, but also significantly inhibited the proliferation of tumor cells when used in combination with pCas9-survivin. At the same time, we also studied the relationship between the molecular weight and therapeutic effect.

Rough Nanovaccines Boost Antitumor Immunity Through the Enhancement of Vaccination Cascade and Immunogenic Cell Death Induction.

Nanovaccines have attracted intense interests for efficient antigen delivery and tumor-specific immunity. It is challenging to develop a more efficient and personalized nanovaccine to maximize all steps of the vaccination cascade by exploiting the intrinsic properties of nanoparticles. Here, biodegradable nanohybrids (MP) composed of manganese oxide nanoparticles and cationic polymers are synthesized to load a model antigen ovalbumin to form MPO nanovaccines. More interestingly, MPO could serve as autologous nanovaccines for personalized tumor treatment taking advantage of in situ released tumor-associated antigens induced by immunogenic cell death (ICD). The intrinsic properties of MP nanohybrids including morphology, size, surface charge, chemical, and immunoregulatory functions are fully exploited to enhance of all steps of the cascade and induce ICD. MP nanohybrids are designed to efficiently encapsulate antigens by cationic polymers, drain to lymph nodes by appropriate size, be internalized by dendritic cells (DCs) by rough morphology, induce DC maturation through cGAS-STING pathway, and enhance lysosomal escape and antigen cross-presentation through the "proton sponge effect". The MPO nanovaccines are found to efficiently accumulate in lymph nodes and elicit robust specific T-cell immune responses to inhibit the occurrence of ovalbumin-expressing B16-OVA melanoma. Furthermore, MPO demonstrate great potential to serve as personalized cancer vaccines through the generation of autologous antigen depot through ICD induction, activation of potent antitumor immunity, and reversal of immunosuppression. This work provides a facile strategy for the construction of personalized nanovaccines by exploiting the intrinsic properties of nanohybrids.

A natural polyphenol-functionalized chitosan/gelatin sponge for accelerating hemostasis and infected wound healing.

Natural polymers have been particularly appealing for constructing hemostatic materials/devices, but it is still desirable to develop new natural polymer-based biomaterials with balanced hemostatic and wound-healing performance. In this work, a natural polyphenol-functionalized chitosan/gelatin sponge (PCGS) was prepared by the lyophilization of a chitosan/gelatin mixture solution (under a self-foaming condition to prepare the CGS) and subsequent chemical cross-linking with procyanidin (PC). Compared with the original CGS, PCGS exhibited an enhanced liquid-absorption ability, reduced surface charges, and similar/low hemolysis rate. Benefiting from such a liquid-absorption ability (∼4000% for whole blood and normal saline) and moderate surface charges, PCGS exhibited high in vitro hemostatic property and promising hemostatic performance in an in vivo femoral-artery-injury model. In addition, PCGS possessed higher antioxidant property and slightly decreased antibacterial ability than CGS, owing to the incorporation of PC. The feasibility of PCGS for treating infected wounds was further confirmed in an in vivo infected-tooth-extraction model, as the typical complication of intractable tooth-extraction bleeding. The present work demonstrated a facile approach for developing multifunctional hemostatic materials through the flexible management of natural polymers and polyphenols.

Recyclable fluorescence sensing based on copper clusters for simultaneous determination of copper ions and ammonia.

A one-step strategy for synthesizing fluorescent copper clusters stabilized by L-cysteine has been successfully established in aqueous solutions. The direct determination of copper ions was realized by the fluorescence enhancement phenomenon caused by the preparation and aggregation process. At the same time, ammonia treatment can lead to rapid fluorescence quenching, resulting from the influence on the aggregation behavior of Cu clusters, while the fluorescence can be recovered by the continuous addition of copper ions. Therefore, a recyclable fluorescence sensing system is constructed for the simultaneous determination of copper ions and ammonia. This method is simple, anti-interference and has been successfully applied to the determination of environmental samples.

Tumor microenvironment-responsive delivery nanosystems reverse immunosuppression for enhanced CO gas/immunotherapy.

Carbon monoxide (CO) gas therapy demonstrates great potential to induce cancer cell apoptosis and antitumor immune responses, which exhibits tremendous potential in cancer treatment. However, the therapeutic efficacy of CO therapy is inhibited by the immunosuppressive tumor microenvironment (TME). Herein, a facile strategy is proposed to construct hollow-structured rough nanoplatforms to boost antitumor immunity and simultaneously reverse immunosuppression by exploring intrinsic immunomodulatory properties and morphological optimization of nanomaterials. The TME-responsive delivery nanosystems (M-RMH) are developed by encapsulating the CO prodrug within hollow rough MnO2 nanoparticles and the subsequent surface functionalization with hyaluronic acid (HA). Rough surfaces are designed to facilitate the intrinsic properties of HA-functionalized MnO2 nanoparticles (RMH) to induce dendritic cell maturation and M1 macrophage polarization by STING pathway activation and hypoxia alleviation through enhanced cellular uptake. After TME-responsive degradation of RMH, controlled release of CO is triggered at the tumor site for CO therapy to activate antitumor immunity. More importantly, RMH could modulate immunosuppressive TME by hypoxia alleviation. After the combination with aPD-L1-mediated checkpoint blockade therapy, robust antitumor immune responses are found to inhibit both primary and distant tumors. This work provides a facile strategy to construct superior delivery nanosystems for enhanced CO/immunotherapy through efficient activation of antitumor immune responses and reversal of immunosuppression.

Laparoscopic intersphincteric resection vs. transanal total mesorectal excision in overweight patients with low rectal cancer.

Objective: Anus-preserving surgery in overweight patients with low rectal cancer has been a challenge due to the narrow operating space. Intersphincteric resection (ISR) was once a standard therapeutic option for low rectal cancer. The effectiveness of transanal total mesorectal excision (taTME) in treating this group of patients remains uncertain as a new surgical strategy. The aim of this study was to evaluate the short-term effects of taTME with ISR in overweight patients with low rectal cancer. Methods: A total of 53 patients with low rectal cancer were treated with taTME in 31 cases and ISR in 22 cases. The surgery-related data, pathological manifestations of surgical specimens, postoperative recovery, and postoperative complications were compared. Results: Patients in both groups completed the surgery successfully. There were no significant differences in operative time, blood loss, anastomotic distance from the anal verge and ileostomy between the two groups (P > 0.05). TaTME group performed or virtually finished resection of the rectal mesentery, and no positive cases of Circumferential Resection Margin (CRM) or Distal Resection Margin (DRM) were detected in either group. The number of lymph nodes found in surgical specimens did not change significantly between the two groups (P = 0.391). In the subgroup analysis, however, more lymph nodes were detected in female patients undergoing taTME than in male patients (P = 0.028). The ISR group took less time to remove the drainage tubes (P = 0.013) and the same results were obtained in both groups of male patients in the subgroup analysis (P = 0.011). There were no statistically significant differences in time to start liquid diet, time to remove catheters, time to start flatus, time to begin ambulation, postoperative hospital stay, and readmission within 30 days after surgery between the two groups (P > 0.05). However, female patients in the taTME group were initiated ambulation earlier than males in the subgroup analysis (P = 0.034). The difference was insignificant in the occurrence of postoperative complications between the two groups (P > 0.05). Conclusion: taTME is safe and feasible for the treatment of overweight patients with low rectal cancer.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

pH-Responsive hyaluronic acid-cloaked polycation/gold nanohybrids for tumor-targeted synergistic photothermal/gene therapy.

The combination of photothermal therapy (PTT) and gene therapy (GT) has attracted intense interest in cancer treatment. However, the lack of long circulation and active tumor targeting reduces the therapeutic efficacy of complementary PTT/GT. In this work, hyaluronic acid (HA)-cloaked gold nanorods-PGED (prepared by ring-opening of polyglycidyl methacrylate (PGMA) with ethylenediamine (ED))/pDNA (AP/pDNA-HA) complexes were prepared to achieve long circulation and tumor targeting for photoacoustic imaging (PAI)-guided synergistic PTT/GT. Gold nanorods endow the complexes with photothermal effect and PAI function. Benefiting from the HA cloak, the AP/pDNA-HA complexes exhibit excellent stability, biocompatibility, long circulation behavior and active targeting. In addition, the pH-responsive characteristic of the Schiff base bonds helps the AP/pDNA-HA complexes to effectively escape from the endosome/lysosome. The antioncogene p53 was employed to investigate the gene transfection efficiency of the delivery system both in vitro and in vivo. The superiority of synergistic PTT/GT is established in a mouse 4T1 breast tumor model. The current study provides a facile strategy for constructing multifunctional gene delivery systems with long circulation and tumor targeting features, which can achieve effective imaging-guided synergistic tumor treatment.

NIR-responsive polydopamine-based calcium carbonate hybrid nanoparticles delivering artesunate for cancer chemo-photothermal therapy.

Artesunate (AS), the first-line treatment of malaria with a satisfactory safety profile, has been repurposed as a potential anticancer candidate as it mainly generates reactive oxygen species (ROS) through its intrinsic endoperoxide bridge reacting with ferrous-based catalysts to suppress cancer cell growth. However, further clinical translation of AS is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/hAS@PEG) for cancer chemo-photothermal therapy, which exerted anticancer effects in the following ways: (1) the heat was generated when PDA was irradiated by near-infrared (NIR) light for photothermal therapy. Meanwhile, the increased temperature accelerated the production of ROS from hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy; (2) hAS-mediated chemotherapy boosted the cancer inhibition effect of photothermal therapy by arousing the intracellular ROS levels in the presence of endogenous ferrous ions and sensitizing cancer cells to thermal ablation; (3) the integration of calcium carbonate into the nanoparticle facilitated the pH-responsive drug release for precise treatment. Such hybrid nanoparticles exhibited a combinational antitumor effect of photothermal therapy and chemotherapy in vivo with no systemic toxicity. Taken together, our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage, which may offer opportunities to pave the way for clinical translation of AS-based nanomedicines. STATEMENT OF SIGNIFICANCE: The clinical translation of artesunate (AS) is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/hAS@PEG) for improved cancer chemo-photothermal therapy. The heat generated from PDA in response to near-infrared light irradiation could locally ablate tumor as well as accelerate the production of ROS by hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy. On the other hand, hAS-based chemotherapy amplified the intracellular oxidative stress, sensitizing cancer cells to thermal ablation. Our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage.

Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol-Mediated Uptake.

New preparation methods of vectors are the key to developing the next generation of biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established to obtain low-toxicity and efficient bioreducible polyguanidines (mPEG225 -b-PSSn , n=13, 26, 39, 75, 105) by regulating the concentration of activated nucleophiles and reaction time under mild reaction conditions. The relationship between the degrees of polymerization and biocompatibility was studied to identify the optimal polyguanidine mPEG225 -b-PSS26 . Such polyguanidine exhibited good in vitro performance in delivering different functional nucleic acids. The impressive therapeutic effects of mPEG225 -b-PSS26 were further verified in the 4T1 tumor-bearing mice as well as the mice with full-thickness skin defects. Controllable disulfide exchange polymerization provides an attractive strategy for the construction of new biomacromolecule delivery systems.

Heparinized anticoagulant coatings based on polyphenol-amine inspired chemistry for blood-contacting catheters.

Blood-contacting catheters occupy a vital position in modern clinical treatment including but not limited to cardiovascular diseases, but catheter-related thrombosis associated with high morbidity and mortality remains a major health concern. Hence, there is an urgent need for functionalized catheter surfaces with superior hemocompatibility that prevent protein adsorption and thrombus formation. In this work, we developed a strategy for constructing a kind of polyphenol-amine coating on the TPU surface (TLA) with tannic acid and lysine via simple dip-coating, inspired by dopamine adhesion. Based on the long-term stability and modifiable properties of TLA coatings, heparin was introduced by an amide reaction to provide anticoagulant activity (TLH). X-ray photoelectron spectroscopy and surface zeta potential measurements fully indicated the successful immobilization of heparin. Water contact angle measurements demonstrated good hydrophilicity and stability for 15 days of TLH coatings. Furthermore, the TLH coatings exhibited significant hemocompatibility and no cytotoxicity. The good antithrombotic properties of the functionalized surfaces were confirmed by an ex vivo blood circulation model. The present work is supposed to find potential clinical applications for preventing surface-induced thrombosis of blood-contacting catheters.