Molecularly imprinted polymers (MIPs) have now earned the reputation as "artificial receptors" or "plastic antibodies". As the mimics of natural receptors, MIPs are reminiscent of some basic ...functions of natural receptors in living systems, e.g., the ability to interact with or recognize cells. The latest decade has witnessed a great advance in MIPs from simple molecular extraction to efficient cell recognition, implying that MIP-based synthetic receptors are approaching to be perfectly functioning replicates of their natural counterparts. With the most emerging development in molecular imprinting, MIP-mediated cell recognition has now shown great promise in cell biology research, theranostics and regenerative medicine. This tutorial review provides a panoramic view of current MIPs for both microorganism and mammalian cell recognition. The most representative developments of MIP-mediated cell recognition, from initial imprinting strategies to eventual bio-related applications, are highlighted.
Microsporidiosis in Humans Han, Bing; Pan, Guoqing; Weiss, Louis M
Clinical microbiology reviews,
12/2021, Volume:
34, Issue:
4
Journal Article
Peer reviewed
Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are about 220 genera and 1,700 species of ...microsporidia, which are classified based on their ultrastructural features, developmental cycle, host-parasite relationship, and molecular analysis. Phylogenetic analysis suggests that microsporidia are related to the fungi, being grouped with the Cryptomycota as a basal branch or sister group to the fungi. Microsporidia can be transmitted by food and water and are likely zoonotic, as they parasitize a wide range of invertebrate and vertebrate hosts. Infection in humans occurs in both immunocompetent and immunodeficient hosts, e.g., in patients with organ transplantation, patients with advanced human immunodeficiency virus (HIV) infection, and patients receiving immune modulatory therapy such as anti-tumor necrosis factor alpha antibody. Clusters of infections due to latent infection in transplanted organs have also been demonstrated. Gastrointestinal infection is the most common manifestation; however, microsporidia can infect virtually any organ system, and infection has resulted in keratitis, myositis, cholecystitis, sinusitis, and encephalitis. Both albendazole and fumagillin have efficacy for the treatment of various species of microsporidia; however, albendazole has limited efficacy for the treatment of Enterocytozoon bieneusi. In addition, immune restoration can lead to resolution of infection. While the prevalence rate of microsporidiosis in patients with AIDS has fallen in the United States, due to the widespread use of combination antiretroviral therapy (cART), infection continues to occur throughout the world and is still seen in the United States in the setting of cART if a low CD4 count persists.
To achieve on‐demand drug release, mesoporous silica nanocarriers as antitumor platforms generally need to be gated with stimuli‐responsive capping agents. Herein, a “smart” mesoporous nanocarrier ...that is gated by the drug itself through a pH‐sensitive dynamic benzoic–imine covalent bond is demonstrated. The new system, which tactfully bypasses the use of auxiliary capping agents, could also exhibit desirable drug release at tumor tissues/cells and enhanced tumor inhibition. Moreover, a facile dynamic PEGylation via benzoic–imine bond further endows the drug‐self‐gated nanocarrier with tumor extracellular pH‐triggered cell uptake and improves therapeutic efficiency in vivo. In short, the paradigm shift in capping agents here will simplify mesoporous nanomaterials as intelligent drug carriers for cancer therapy. Moreover, the self‐gated strategy in this work also shows general potential for self‐controlled delivery of natural biomolecules, for example, DNA/RNA, peptides, and proteins, due to their intrinsic amino groups.
A drug‐self‐gated strategy for mesoporous nanocarrier could achieve on‐demand drug release at tumor tissue/cells and improved antitumor efficiency. The key is using a pH‐sensitive benzoic–imine bond for dynamic conjugation of amino‐containing drug molecules (i.e., doxorubicin) on the pore outlets.
Multifunctional nanomaterials with efficient tumor‐targeting and high antitumor activity are highly anticipated in the field of cancer therapy. In this work, a synergetic tumor‐targeted, ...chemo‐photothermal combined therapeutic nanoplatform based on a dynamically PEGylated, borate‐coordination‐polymer‐coated polydopamine nanoparticle (PDA@CP‐PEG) is developed. PEGylation on the multifunctional nanoparticles is dynamically achieved via the reversible covalent interaction between the surface phenylboronic acid (PBA) group and a catechol‐containing poly(ethylene glycol) (PEG) molecule. Due to the acid‐labile PBA/catechol complex and the weak‐acid‐stable PBA/sialic acid (SA) complex, the nanoparticles can exhibit a synergetic targeting property for the SA‐overexpressed tumor cells, i.e., the PEG‐caused “passive targeting” and PBA‐triggered “active targeting” under the weakly acidic tumor microenvironment. In addition, the photothermal effect of the polydopamine core and the doxorubicin‐loading capacity of the porous coordination polymer layer endow the nanoparticles with the potential for chemo‐photothermal combination therapy. As expected, the in vitro and in vivo studies both verify that the multifunctional nanoparticles possess relatively lower systematic toxicity, efficient tumor targeting ability, and excellent chemo‐photothermal activity for tumor inhibition. It is believed that these multifunctional nanoparticles with synergetic tumor targeting property and combined therapeutic strategies would provide an insight into the design of a high‐efficiency antitumor nanoplatform for potential clinical applications.
Double‐insurance: A synergetic tumor targeted and chemo‐photothermal cancer therapeutic nanoplatform based on dynamically PEGylated and borate‐coordination‐polymer‐coated polydopamine nanoparticles is demonstrated here. The combination of PEGylation‐caused “passive targeting” and phenylboronic acid‐triggered “active targeting” endow the antitumor nanoplatform with low systematic toxicity, efficient tumor targeting, and excellent antitumor activity in vivo.
In river water, milk, and bovine serum, molecularly imprinted polymer nanoparticles with hydrophilic polymer brushes showed excellent molecular recognition (see picture). Readily prepared by ...precipitation polymerization with a macromolecular chain‐transfer agent, such nanoparticles are promising alternatives to antibodies for many applications owing to their superior dispersion and binding properties in biological matrices.
In recent years, along with the rapid development of relevant biological fields, there has been a tremendous motivation to combine molecular imprinting technology (MIT) with biosensing. In this ...situation, bioprobes and biosensors based on molecularly imprinted polymers (MIPs) have emerged as a reliable candidate for a comprehensive range of applications, from biomolecule detection to drug tracking. Unlike their precursors such as classic immunosensors based on antibody binding and natural receptor elements, MIPs create complementary cavities with stronger binding affinity, while their intrinsic artificial polymers facilitate their use in harsh environments. The major objective of this work is to review recent MIP bioprobes and biosensors, especially those used for biomolecules and drugs. In this review, MIP bioprobes and biosensors are categorized by sensing method, including optical sensing, electrochemical sensing, gravimetric sensing and magnetic sensing, respectively. The working mechanism(s) of each sensing method are thoroughly discussed. Moreover, this work aims to present the cutting-edge structures and modifiers offering higher properties and performances, and clearly point out recent efforts dedicated to introduce multi-sensing and multi-functional MIP bioprobes and biosensors applicable to interdisciplinary fields.
Narrowly dispersed water‐compatible molecularly imprinted polymer (MIP) microspheres with surface‐grafted hydrophilic polymer brushes were synthesized by RAFT precipitation polymerization (RAFTPP) ...mediated by hydrophilic macromolecular chain‐transfer agents (Macro‐CTA). The easy availability of hydrophilic Macro‐CTAs and the versatility of the RAFTPP technique make it a general and promising strategy. CDB=cumyl dithiobenzoate.
We report here an injectable, self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic wound regeneration. The hydrogel was prepared by coordinative cross-linking ...of multi-arm thiolated polyethylene glycol (SH-PEG) with silver nitrate (AgNO3). Due to the dynamic nature of Ag-S coordination bond and bacteria-killing activity of Ag+, the resultant coordinative hydrogel featured self-healing, injectable and antibacterial properties. In this study, we synchronously loaded an angiogenic drug, desferrioxamine (DFO), in the coordinative hydrogel during cross-linking. We finally obtained a multifunctional hydrogel that is manageable, resistant to mechanical irritation, antibacterial and angiogenic in vitro. Our in vivo studies further demonstrated that the injectable self-healing hydrogel could efficiently repair diabetic skin wounds with low bacteria-infection and enhance angiogenic activity. In short, besides diabetic skin wound repair, such dynamic multifunctional hydrogel scaffolds would show great promise in the regeneration of different types of exposed wounds, in particular, in situations with disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation.Wound repair: Self-healing materials step up to save feetSoft gels that can be injected into wounds to protect them from infection and promote blood vessel formation may benefit diabetic foot care. To create a scaffold-like substance tough enough to handle the mechanical stresses that feet experience, Hao Chen and colleagues from the Shanghai Jiao Tong University and Jiangsu University in China linked polyethylene glycol chains together using silver–sulfur chemical bonds that quickly re-join after being broken. This strategy produced a gel that returns to its original shape after being sliced or twisted, and which can be loaded with drugs to aid vascular network growth. Experiments in rat models revealed that direct injection of drug-containing gels to wounds decreased their size by 20% compared to control groups. The intrinsic antibacterial nature of silver ions also generated sterile inhibition zones around gel-treated lesions.
With the massive use of medical implants (e.g., metals, polymers and ceramics) in orthopedic and cardiovascular surgery, surface biomodification of these exogenous biomaterials has caused growing ...concern, for the purpose of improving their functions and avoiding surgical failure. Mussel-inspired chemistry (i.e., dopamine self-polymerization) based on covalent and noncovalent catechol-mediated molecular adhesion exhibits versatility in surface biomodification. However, the inevitable consumption of amino and thiol groups in the bioactive molecules still makes this robust surface chemistry in a dilemma. Taking this biomimetic strategy one step further, synthetic peptides with multiple DOPA (3,4-Dihydroxy-L-phenylalanine) units were recently extensively studied. Since the catecholic DOPA unit is abundant in the main component of mussel foot protein, these peptides are able to adhere onto various substrates. In addition, these mussel-inspired peptides could be flexibly linked with bioactive or attachable molecules, which can bypass the consumption of active groups in the second-step biomodification of poly(dopamine) method. Owing to these superiorities, mussel adhesive peptides mimics with diversified bioactivity are widely used for surface modification of medical implants to regulate different cell responses. The purpose of this review is to provide a brief overview of the latest developments in the surface bioengineering of medical implants using these mussel adhesive peptides mimics as a medium. We anticipate that the stepwise discussions from peptide mimicking and synthesis to surface bioactivity adaptation in different implants may also encourage researchers to innovate current mussel-inspired peptides at molecular level and expand their applications in the field of biomaterial engineering.
•Mussel-inspired peptide mimics were well studied for surface bioengineering of medical implants.•The synthetic methods of these mussel-inspired peptide mimics are briefly summarized.•Mussel-inspired peptide mimics with various biological effects on different medical implants are elaborated and discussed.
The review aims to summarize recent reports of stimuli-responsive nanomaterials based on molecularly imprinted polymers (MIPs) and discuss their applications in biomedicine. In the past few decades, ...MIPs have been proven to show widespread applications as new molecular recognition materials. The development of stimuli-responsive nanomaterials has successfully endowed MIPs with not only affinity properties comparable to those of natural antibodies but also the ability to respond to external stimuli (stimuli-responsive MIPs). In this review, we will discuss the synthesis of MIPs, the classification of stimuli-responsive MIP nanomaterials (MIP-NMs), their dynamic mechanisms, and their applications in biomedicine, including bioanalysis and diagnosis, biological imaging, drug delivery, disease intervention, and others. This review mainly focuses on studies of smart MIP-NMs with biomedical perspectives after 2015. We believe that this review will be helpful for the further exploration of stimuli-responsive MIP-NMs and contribute to expanding their practical applications especially in biomedicine in the near future.
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