Glucose-responsive materials have attracted great intention in recent years due to their potential application in drug delivery. Phenylboronic acid-containing materials have been most widely studied ...and used in construction of glucose-responsive system for insulin delivery. This review covers the recent advances in synthesis of phenylboronic acid-based glucose-responsive materials, especially in forms of nanogels (microgels), micelles, vesicles, and mesoporous silica nanoparticles. Applications of these nanomaterials in drug delivery are discussed.
This review highlights the recent advances in synthesis of phenylboronic acid-based glucose-responsive nanoparticles and their applications in drug delivery.
Planar donor and acceptor (D–A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular ...motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an “abnormal” strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D–A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.
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IJS, KILJ, NUK, PNG, UL, UM
Folding and unfolding are essential ways for a protein to regulate its biological activity. The misfolding of proteins usually reduces or completely compromises their biological functions, which ...eventually causes a wide range of diseases including neurodegeneration diseases, type II diabetes, and cancers. Therefore, materials that can regulate protein folding and maintain proteostasis are of significant biological and medical importance. In living organisms, molecular chaperones are a family of proteins that maintain proteostasis by interacting with, stabilizing, and repairing various non‐native proteins. In the past few decades, efforts have been made to create artificial systems to mimic the structure and biological functions of nature chaperonins. Herein, recent progress in the design and construction of materials that mimic different kinds of natural molecular chaperones is summarized. The fabrication methods, construction rules, and working mechanisms of these artificial chaperone systems are described. The application of these materials in enhancing the thermal stability of proteins, assisting de novo folding of proteins, and preventing formation of toxic protein aggregates is also highlighted and explored. Finally, the challenges and potential in the field of chaperone‐mimetic materials are discussed.
Artificial systems that mimic the functions of molecular chaperones are promising for biomedical applications. The recent state‐of‐the‐art progress in artificial chaperone systems and their applications are systematically summarized, giving deep insight into the principles and trends for the development of novel artificial chaperone systems to solve essential problems in biomedicine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The EPR effect of 41 renal tumors collected from clinical patients were analyzed via perfusion strategy, correlating the EPR effect in human tumors with that in animal models and confirming that more ...than 87 % of the examined renal tumors possess the considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients.
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•An ex vivo perfusion model was developed for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT).•The EPR in human solid tumors was positively correlated with that in animal models.•Considerable EPR effect was observed in more than 87% of human renal tumors, which showed significant diversity and heterogeneity.
The enhanced permeability and retention (EPR) effect in human solid tumors is being increasingly questioned due to the failure of many nanomedicines in their clinical translation. Herein, we developed an ex vivo perfusion model for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT), proving the EPR in human solid tumors and correlating the EPR effect in human tumors with that in animal models. Unexpectedly, more than 87 % of human renal tumors displayed a considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients. For the first time, we unraveled that the EPR effect in renal tumors was positively correlated with the tumor size, and tumors from male patients exhibited a significantly higher EPR effect. This ex vivo model provides an efficient strategy for investigating the EPR effect in human tumors. Our results may provide a theoretical basis for the development of anticancer nanomedicines in the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The concept of trade-off effects of polymeric nano-medicine in anti-cancer therapy is proposed.•Different trade-off effects of polymeric nano-medicine in anti-cancer therapy are summarized with ...emphasis on the conflict between prolonging blood circulation and enhancing cellular uptake.•Tailor-made nano-carriers with charge-reversal, shell-shedding, and surface assembling abilities are discussed in detail for overcoming the trade-off effect between prolonged circulation time and enhanced cellular uptake.
Polymeric nano-medicine has been widely studied in anti-cancer therapy and great achievements have been made over the past three decades. Though side effects of drugs such as toxicity are greatly reduced, the therapeutic efficacy has not been improved significantly so far, which maybe mainly because of the trade-off effects between oppositely required functions of nano-medicines at different steps in drug delivery, such as prolonged blood circulation vs. enhanced cellular uptake, and stable drug retention in transit vs. responsive release in cancer cells. To overcome the trade-off effect between blood circulation and cellular uptake, different functionalities, including surface charge reversal, shell-shedding, and surface self-assembly properties, have been designed for nano-carriers. The starting point of these strategies is endowing the nano-carriers with stealth character during blood circulation while transforming them into a more cell-interactive state to enhance cellular uptake. This review summaries the recent advances in designing powerful nano-carriers to overcome the trade-off effect between prolonging blood circulation and enhancing cellular uptake to improve the anti-cancer therapeutic efficacy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bacterial infections are mostly due to bacteria in their biofilm mode‐of‐growth, making them recalcitrant to antibiotic penetration. In addition, the number of bacterial strains intrinsically ...resistant to available antibiotics is alarmingly growing. This study reports that micellar nanocarriers with a poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to their biological invisibility. However, when the shell is complemented with poly(β‐amino ester), these mixed‐shell micelles become positively charged in the low pH environment of a biofilm, allowing not only their penetration but also their accumulation in biofilms without being washed out, as do single‐shell micelles lacking the pH‐adaptive feature. Accordingly, bacterial killing of multidrug resistant staphylococcal biofilms exposed to protoporphyrin IX‐loaded mixed‐shell micelles and after light‐activation is superior compared with single‐shell micelles. Subcutaneous infections in mice, induced with vancomycin‐resistant, bioluminescent staphylococci can be eradicated by daily injection of photoactivatable protoporphyrin IX‐loaded, mixed‐shell micelles in the bloodstream and light‐activation at the infected site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are degraded in the liver and spleen and cleared from the body through the kidneys. Thus, adaptive micellar nanocarriers loaded with light‐activatable antimicrobials constitute a much‐needed alternative to current antibiotic therapies.
Photodynamic treatment with protoporphyrin IX‐loaded micelles is successful in eradicating a subcutaneous, multidrug‐resistant infection in mice, while unused micelles are demonstrated to be cleared from the blood circuation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Programmable self‐assembly of peptides into well‐defined nanostructures represents one promising approach for bioinspired and biomimetic synthesis of artificial complex systems and functional ...materials. Despite the progress made over the past two decades in the development of strategies for precise manipulation of the self‐assembly of peptides, there is a remarkable gap between current peptide assemblies and biological systems in terms of structural complexity and functions. Here, the concept of peptide tectonics for the creation of well‐defined nanostructures predominately driven by the complementary association at the interacting interfaces of tectons is introduced. Peptide tectons are defined as peptide building blocks exhibiting structural complementarity at the interacting interfaces of commensurate domains and undergoing programmable self‐assembly into defined supramolecular structures promoted by complementary interactions. Peptide tectons are categorized based on their conformational entropy and the underlying mechanism for the programmable self‐assembly of peptide tectons is highlighted focusing on the approaches for incorporating the structural complementarity within tectons. Peptide tectonics not only provides an alternative perspective to understand the self‐assembly of peptides, but also allows for precise manipulation of peptide interactions, thus leading to artificial systems with advanced complexity and functions and paves the way toward peptide‐related functional materials resembling natural systems.
Peptide tectons, referred to as peptide building blocks with structural complementarity, undergo programmable self‐assembly driven by complementary interactions at predictable interfaces between incorporated domains. The concept of peptide tectonics is introduced for the creation of well‐defined peptide nanostructures with rationally tailored structural features, thus potentially paving the way for developing functional materials resembling natural systems.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Isopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers ...suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.
Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to antibiotic treatment of ...infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core. Micelles are self-assembled, spherical core-shell structures composed of single layers of surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core. Liposomes are composed of lipids, self-assembled into bilayers. The hydrophilic head of the lipids determines the surface properties of liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the phospholipid bilayer. Nanotechnology-derived liposomes can be prepared with diameters <100-200 nm, required to prevent reticulo-endothelial rejection and allow penetration into infectious-biofilms. However, surface-functionalization of liposomes is considerably more difficult than of micelles, which explains while self-targeting, pH-responsive liposomes that find their way through the blood circulation toward infectious-biofilms are still challenging to prepare. Equally, development of liposomes that penetrate over the entire thickness of biofilms to provide deep killing of biofilm inhabitants still provides a challenge. The liposomal phospholipid bilayer easily fuses with bacterial cell membranes to release high antimicrobial-doses directly inside bacteria. Arguably, protection against de-activation of antibiotics in liposomal nanocarriers and their fusogenicity constitute the biggest advantage of liposomal antimicrobial carriers over antimicrobials free in solution. Many Gram-negative and Gram-positive bacterial strains, resistant to specific antibiotics, have been demonstrated to be susceptible to these antibiotics when encapsulated in liposomal nanocarriers. Recently, also progress has been made concerning large-scale production and long-term storage of liposomes. Therewith, the remaining challenges to develop self-targeting liposomes that penetrate, accumulate and kill deeply in infectious-biofilms remain worthwhile to pursue.
Photothermal therapy (PTT) has emerged as an attractive technique for the treatment of bacterial infections. However, the uncontrolled heat generation in conventional PTT inevitably causes thermal ...damages to healthy tissues and/or organs. It is thus essential to develop a smart and universal strategy to regulate the photothermal equilibrium temperature to a preset safe threshold. Herein, a thermoresponsive hydrogel‐enabled thermostatic PTT system for enhanced healing of bacteria‐infected wounds is reported. In this system, the near‐infrared (NIR)‐triggered heat generation by photothermal nanomaterials is spontaneously transferred to a thermoresponsive hydrogel with a lower critical solution temperature (LCST), leading to its rapid phase transition by forming considerable light‐scattering centers to block NIR penetration. Such a dynamic and reversible process automatically regulates the photothermal equilibrium temperature to the phase‐transition point of the LCST‐type hydrogel. In contrast to temperature‐uncontrolled conventional PTT with severe thermal damages, the thermoresponsive hydrogel‐enabled thermostatic PTT provides effective protection on healthy tissues and/or organs, which remarkably accelerates wound healing by efficient bacterial eradication. This study establishes a smart, simple and universal PTT platform, holding great promise in the safe and efficient treatment of bacterial skin infections.
A thermoresponsive hydrogel‐enabled thermostatic photothermal therapy system is reported for enhanced healing of bacteria‐infected wounds. Taking advantage of the reversible phase transition properties of the hydrogel, the system photothermal equilibrium temperature can be automatically regulated to the phase‐transition point of the hydrogel, which is employed for smart photothermal therapy with negligible thermal damages to healthy tissues and/or organs.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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