Selection of Affinity Reagents to Neutralize the Hemolytic Toxicity of Melittin Based on a Self-Assembled Nanoparticle Library

Poisoning is a leading cause of admission to medical emergency departments and intensive care units. Supramolecular detoxification, which involves injecting supramolecular receptors that bind with toxins to suppress their biological activity, is an emerging strategy for poisoning treatment; it has few requirements and a broad application scope. However, it is still a formidable challenge to design supramolecular therapeutic materials as an antidote to macromolecular toxins, because the large size, flexible conformation, and presence of multiple and diverse binding sites of biomacromolecules hinder their recognition. Herein, a supramolecular antidote to macromolecular toxins is developed through the coassembly of macrocyclic amphiphiles, relying on heteromultivalent recognition between the coassembled components and toxic macromolecules. The coassembly of amphiphilic cyclodextrin and calixarene strongly and selectively captures melittin, a toxin studied herein; this imparts various therapeutic effects such as inhibiting the interactions of melittin with cell membranes, alleviating melittin cytotoxicity and hemolytic toxicity, reducing the mortality rate of melittin-poisoned mice, and mitigating damage to major organs. The use of the proposed antidote overcomes the limitation of supramolecular detoxification applicability to only small-molecular toxins. The antidote can also detoxify other macromolecular toxins as long as selective and strong binding is achieved because of the coassembling tunability.

show abstract

“…Melittin can also lyse red blood cell (RBC) membranes. [25] Therefore, we evaluated the ability of CCA-CD to reduce Adv. Mater.…”

Section: Resultsmentioning

confidence: 99%

“…Melittin can also lyse red blood cell (RBC) membranes. [ 25 ] Therefore, we evaluated the ability of CCA‐CD to reduce the hemolytic toxicity of melittin by conducting a hemolysis assay. A large amount of hemoglobin was released because of the lysis of the RBC membrane after treatment with melittin (2.00 × 10 −6 m , Figure 1f,g).…”

Section: Resultsmentioning

confidence: 99%

A Supramolecular Antidote to Macromolecular Toxins Prepared through Coassembly of Macrocyclic Amphiphiles

Pan

Yue

et al. 2021

Advanced Materials

View full text Add to dashboard Cite

show abstract

“…β-Cyclodextrin (β-CDP), an easily available polymer material, has a ring-shaped truncated cone topology with a hydrophobic cavity to non-covalently contain diverse guest molecules [ 120 ]. Xu et al [ 90 ] established a library of self-assembled MEL nanoparticles based on β-CDPs and functional monomer adamantane derivatives (Ad-Ds). The cytotoxicity of 30 μg/mL MEL with 2 mmol/mL nanoparticle decreased by sixfold compared with that of free MEL.…”

Section: Delivery Vehicles For Melittinmentioning

confidence: 99%

Melittin-Based Nano-Delivery Systems for Cancer Therapy

et al. 2022

View full text Add to dashboard Cite

Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes, hemolytic activity, and potential anti-tumor properties. However, the clinical application of melittin is restricted due to its severe hemolytic activity. Different nanocarrier systems have been developed to achieve stable loading, side effects shielding, and tumor-targeted delivery, such as liposomes, cationic polymers, lipodisks, etc. In addition, MEL can be modified on nano drugs as a non-selective cytolytic peptide to enhance cellular uptake and endosomal/lysosomal escape. In this review, we discuss recent advances in MEL’s nano-delivery systems and MEL-modified nano drug carriers for cancer therapy.

show abstract

“…CD is a slightly conical circular ring with hydrophilic outer edge and hydrophobic inner cavity, combining with organic and inorganic molecules, to form nanosystems. It can improve the stability, solubility, and dissolution rate of hydrophobic materials, reducing the side effects of peptides and achieving the controlled drug release effect, with an antibacterial and anti-inflammatory effect, such as the ingredients in aloe vera gum ( Zhang et al, 2018 ; Gao et al, 2019 ; Lu et al, 2019 ; Xu Y. et al, 2020 ). Therefore, CD has been used in the field of cosmetic, medicine, and food, with great value in the field of AMP coating.…”

Section: Organic Materials Nanosystems Containing Antimicrobial Peptidesmentioning

confidence: 99%

Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

Yang

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

The security issue of human health is faced with dispiriting threats from multidrug-resistant bacteria infections induced by the abuse and misuse of antibiotics. Over decades, the antimicrobial peptides (AMPs) hold great promise as a viable alternative to treatment with antibiotics due to their peculiar antimicrobial mechanisms of action, broad-spectrum antimicrobial activity, lower drug residue, and ease of synthesis and modification. However, they universally express a series of disadvantages that hinder their potential application in the biomedical field (e.g., low bioavailability, poor protease resistance, and high cytotoxicity) and extremely waste the abundant resources of AMP database discovered over the decades. For all these reasons, the nanostructured antimicrobial peptides (Ns-AMPs), based on a variety of nanosystem modification, have made up for the deficiencies and pushed the development of novel AMP-based antimicrobial therapies. In this review, we provide an overview of the advantages of Ns-AMPs in improving therapeutic efficacy and biological stability, reducing side effects, and gaining the effect of organic targeting and drug controlled release. Then the different material categories of Ns-AMPs are described, including inorganic material nanosystems containing AMPs, organic material nanosystems containing AMPs, and self-assembled AMPs. Additionally, this review focuses on the Ns-AMPs for the effect of biological activities, with emphasis on antimicrobial activity, biosecurity, and biological stability. The “state-of-the-art” antimicrobial modes of Ns-AMPs, including controlled release of AMPs under a specific environment or intrinsic antimicrobial properties of Ns-AMPs, are also explicated. Finally, the perspectives and conclusions of the current research in this field are also summarized.

show abstract

Selection of Affinity Reagents to Neutralize the Hemolytic Toxicity of Melittin Based on a Self-Assembled Nanoparticle Library

Cited by 14 publications

References 42 publications

A Supramolecular Antidote to Macromolecular Toxins Prepared through Coassembly of Macrocyclic Amphiphiles

A Supramolecular Antidote to Macromolecular Toxins Prepared through Coassembly of Macrocyclic Amphiphiles

Melittin-Based Nano-Delivery Systems for Cancer Therapy

Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

Contact Info

Product

Resources

About