Organic Nanoplatforms for Iodinated Contrast Media in CT Imaging.

X-ray computed tomography (CT) imaging can produce three-dimensional and high-resolution anatomical images without invasion, which is extremely useful for disease diagnosis in the clinic. However, its applications are still severely limited by the intrinsic drawbacks of contrast media (mainly iodinated water-soluble molecules), such as rapid clearance, serious toxicity, inefficient targetability and poor sensitivity. Due to their high biocompatibility, flexibility in preparation and modification and simplicity for drug loading, organic nanoparticles (NPs), including liposomes, nanoemulsions, micelles, polymersomes, dendrimers, polymer conjugates and polymeric particles, have demonstrated tremendous potential for use in the efficient delivery of iodinated contrast media (ICMs). Herein, we comprehensively summarized the strategies and applications of organic NPs, especially polymer-based NPs, for the delivery of ICMs in CT imaging. We mainly focused on the use of polymeric nanoplatforms to prolong circulation time, reduce toxicity and enhance the targetability of ICMs. The emergence of some new technologies, such as theragnostic NPs and multimodal imaging and their clinical translations, are also discussed.

Screening and Matching Amphiphilic Cationic Polymers for Efficient Antibiosis.

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure-antibacterial activity relationship of these cationic polymers was investigated against E. coli and S. aureus, including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB35/T57) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB33/T56). Furthermore, mPB35/T57 with appropriate mole fraction of alkyl side chains (falkyl = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both E. coli (MIC = 8 µg/mL, selectivity > 250) and S. aureus (MIC = 4 µg/mL, selectivity > 500). More importantly, mPB35/T57 could effectively eradicate E. coli biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB35/T57 provided valuable information for improving the antibacterial activity of cationic polymers.

Janus polyurethane sponge as an antibiofouling, antibacterial, and exudate-managing dressing for accelerated wound healing.

The non-fouling condition, bacteria-free environment and suitable moisture at wound site are crucial for chronic wound healing. However, it remains highly meaningful yet challenging to develop wound dressings that can simultaneously achieve these desirable functions. In this work, a kind of multifunctional Janus polyurethane sponge (Janus-PU) was designed and fabricated by coating near-infrared (NIR)-responsive and superhydrophobic nanoparticles (F-ZnO@Ag NPs) on one surface of sponge. The nano-functionalized outer layer can endow Janus-PU with superhydrophobic antifouling property for preventing bacterial colonization and broad-spectrum antibacterial activity due to the presence of Ag NPs. Especially, the synergistic combination of asymmetric structure and strong NIR photothermal effect can impart Janus-PU with NIR-controlled unidirectional exudate removal, thus achieving an optimal wetting environment for wound healing. The mice full-thickness skin acute wounds treated with Janus-PU under NIR irradiation showed superior anti-infection and healing effect compared to the commercial dressings. Significantly, the treatment using Janus-PU with NIR irradiation can accelerate the recovery of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic chronic wounds due to the synergistic effect of antibiofouling, antibacterial and exudate-managing. The Janus-PU as a promising multifunctional dressing can prevent bacterial invasion and create an appropriate environment for wound healing, providing an effective solution for intractable wounds and infections. STATEMENT OF SIGNIFICANCE: The development of advanced wound dressings to ensure non-fouling condition, bacteria-free environment and suitable moisture is crucial for chronic wound healing. However, it remains a considerable challenge to simultaneously integrate antibiofouling, antibacterial and exudate-managing properties into a single dressing. In this work, we developed a kind of multifunctional Janus polyurethane sponge (Janus-PU) by a single-sided superhydrophobic modification strategy, which can simultaneously achieve superhydrophobic antifouling property, effective broad-spectrum antibacterial and near-infrared controlled exudate removal. The Janus-PU designed herein can not only create an optimal environment for accelerated wound healing, but also avoid frequent dressing replacement, thus providing an ideal material system for intractable wounds and infections.

Polymers for Improved Delivery of Iodinated Contrast Agents.

X-ray computed tomography (CT), as one of the most widely used noninvasive imaging modalities, can provide three-dimensional anatomic details with high resolution, which plays a key role in disease diagnosis and treatment assessment. However, although they are the most prevalent and FDA-approved contrast agents, iodinated water-soluble molecules still face some challenges in clinical applications, such as fast clearance, serious adverse effects, nonspecific distribution, and low sensitivity. Because of their high biocompatibility, tunable designability, controllable biodegradation, facile synthesis, and modification capability, the polymers have demonstrated great potential for efficient delivery of iodinated contrast agents (ICAs). Herein, we comprehensively summarized the applications of multifunctional polymeric materials for ICA delivery in terms of increasing circulation time, decreasing nephrotoxicity, and improving the specificity and sensitivity of ICAs for CT imaging. We mainly focused on various iodinated polymers from the aspects of preparation, functionalization, and application in medical diagnosis. Future perspectives for achieving better imaging and clinical translation are also discussed to motivate new technologies and solutions.

Strategies and applications of covalent organic frameworks as promising nanoplatforms in cancer therapy.

Cancer nanomedicine is the best option to face the limits of conventional chemotherapy and phototherapy methods, and thus the intensive quest for new nanomaterials to improve therapeutic efficacy and safety is still underway. Owing to their low density, well-defined structures, large surface area, finely tunable pore size, and metal ion free features, covalent organic frameworks (COFs) have been extensively studied in many research fields. The recent great interest in nanoscale COFs to improve the properties of bulk COFs has led to broadening of their applicability in the biomedical field, such as nanocarriers with an outstanding loading capacity and efficient delivery of therapeutic agents, smart theranostic nanoplatforms with excellent stability, high ROS generation, light-to-heat conversion capabilities, and different response and diagnostic characteristics. The COFs and related nanoplatforms with a wide variety of designability and functionalization have opened up a new avenue for exciting opportunities in cancer therapy. Herein we review the state-of-the-art technical and scientific developments in this emerging field, focusing on the overall progress addressed so far in building versatile COF-based nanoplatforms to enhance chemotherapy, photodynamic/photothermal therapy, and combination. Future perspectives for achieving the synergistic effect of cancer elimination and clinical translation are further discussed to motivate future contributions and explore new possibilities.

Multi-transformable nanocarrier with tumor extracellular acidity-activated charge reversal, size reduction and ligand reemergence for in vitro efficient doxorubicin loading and delivery.

Various nanoparticles as drug delivery system provide significant improvements in the cancer treatment. However, their clinical success remains elusive in large part due to their inability to overcome both systemic and tumor tissue barriers. The nanosystems with nanoproperty-transformability (surface, size, stability and target) hold great promise for achieving enhanced delivery efficacy. However, currently available systems that are mainly polymer-based assemblies usually suffer from the intrinsic drawbacks of poor stability, premature leakage and low drug loading as well as limited transformability. In this study, we designed a facile strategy to build a novel multi-transformable MSNs@GO nanosystem for efficient doxorubicin (DOX) loading and delivery. This novel nanosystem was well characterized and investigated in vitro. The results indicated that the MSNs@GO can realize a very high drug loading ability due to the large pore surface area of MSNs and the demonstrated donor-acceptor (boron­nitrogen) coordination interactions between phenylboronic acid-containing nanocarriers and electron donor-containing DOX. More importantly, the novel nanocarriers can simultaneously achieve charge reversal, size reduction and ligand reemergence by shielding/deshielding transition via acid-cleavable dynamic boronate bonds under in vitro simulated acidic microenvironment of tumor tissues, opening a new avenue for improving delivery efficiency of chemotherapeutics.

Layer-by-layer zwitterionic modification of diverse substrates with durable anti-corrosion and anti-fouling properties.

A versatile coating strategy, which is suitable for the anti-corrosion and anti-fouling modification of chemically distinct substrates, is crucial in many industries. The immobilization of zwitterionic polymers onto the surface has been proven to be an excellent approach for the improvement of antibiofouling potency. However, the anti-corrosion property has not always been considered simultaneously. Herein, a layer-by-layer (LBL) zwitterionic surface modification strategy was proposed: the surface was first coated with a polydopamine (PDA) layer for anti-corrosion; then, by self-assembling a monolayer of 3-aminopropyl triethoxysilane (APTES), the anti-corrosion ability was further enhanced and the efficiency of grafting was improved; thereafter, by immobilizing the zwitterionic polysulfobetaine (PSB) polymer brush layer, the surface could effectively repel biofouling. The surface chemical composition and morphology characterization was performed by using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle measurements, demonstrating that the modification was stepwise introduced onto the surface. The thickness of coating was observed and measured by SEM cross-sectional analysis. In vitro studies revealed that the PSB coated surfaces dramatically reduced the adhesion of bovine serum albumin (BSA), bovine plasma fibrinogen (Fg), bovine γ-globulin (γ-GL), the mixture of these proteins, fibroblasts, E. coli and S. aureus with superior cytocompatibility and hemocompatibility. Moreover, the electrochemical impedance spectroscopy and acidic corrosion studies indicated that an excellent and durable anti-corrosion property was established successfully on the surfaces of stainless steel, cotton textile and wood plates, confirming the feasibility of the LBL surface modification strategy. Significantly, this LBL surface chemistry may be widely applied for the modification of other materials, such as biosensors, biomedical implants and/or devices, and marine equipment.