Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers

Yang, Su; Dong, He

doi:10.1039/d0ra04748a

Cited by 8 publications

(15 citation statements)

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“…This peptide is known to self-assemble into a sandwich-like β-sheet nanofiber in which the hydrophobic residues are buried within the sandwich structure and shielded from the aqueous environment. [43][44][45][46][47] By replacing some of the hydrophobic residues on MDPs with these ionizable amino acids, nanofibers with an ionizable hydrophobic core can be generated to undergo pH-induced self-assembly or disassembly. While the pK a of a free tertiary amine is typically found in the basic region, we anticipate the local hydrophobic environment can shift the pK a of these tertiary-amine containing residues toward the biologically relevant pH at a near neutral or weakly acidic range, which is critical for practical applications such as tumor-acidity targeted drug delivery or proton transport.…”

Section: Introductionmentioning

confidence: 99%

“…As a proof‐of‐concept demonstration, we introduced these residues in a multidomain peptide (MDP). This peptide is known to self‐assemble into a sandwich‐like β‐sheet nanofiber in which the hydrophobic residues are buried within the sandwich structure and shielded from the aqueous environment [43–47] . By replacing some of the hydrophobic residues on MDPs with these ionizable amino acids, nanofibers with an ionizable hydrophobic core can be generated to undergo pH‐induced self‐assembly or disassembly.…”

Section: Introductionmentioning

confidence: 99%

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Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Asokan-Sheeja

Yang

Adones

et al. 2022

Chemistry An Asian Journal

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Self‐assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH‐responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH‐responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain. Through a combined experimental and computational investigation, we demonstrate that these residues can be accommodated and stabilized within the internal hydrophobic compartment of the peptide assembly. The hydrophobic microenvironment shifts their pKa significantly from a basic pH typically found for free amines to a more biologically relevant pH in the weakly acidic range. The pH‐induced ionization and ionization‐dependent self‐assembly and disassembly are thoroughly investigated and correlated with the biological activity of the assembly. This new approach has unique advantages in tuning the pH‐responsiveness of self‐assembled peptides across a large pH range in a complex biological environment. We anticipate the ionizable amino acids developed here can be widely applicable to the synthesis and self‐assembly of many amphiphilic peptides with endowed pH‐responsive properties to enhance their biological activities toward applications ranging from targeted therapeutic delivery to proton transport.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Asokan-Sheeja

Yang

Adones

et al. 2022

Chemistry An Asian Journal

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“…Most NPs are internalized by cells using endocytic or phagocytic pathways, including clathrin, caveolin, micropinocytosis, and other energy-independent pathways. Previous studies have showed that self-assembled NFs undergo cell uptake by micropinocytosis in HeLa cells . Given the new structure and composition of NCs, we screened the NCs for their uptake mechanisms using various endocytosis inhibitors.…”

Section: Resultsmentioning

confidence: 99%

“…Fluorescein terminated peptides were synthesized as previously described by Yang and Dong . 5(6)-Carboxyl fluorescein (FITC)-tagged peptides were mixed with Rho B PLGA NPs.…”

Section: Methodsmentioning

confidence: 99%

Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery

Chintapula

Yang

Nguyen

et al. 2022

ACS Appl. Mater. Interfaces

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Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications. Inspired by recent advances of CPPs and CPPfunctionalized nanoparticles, in this work, we demonstrate a novel nanocomposite consisting of fiber-forming supramolecular CPPs that are coated onto polylactic-glycolic acid (PLGA) nanoparticles to enhance pulmonary drug delivery. These nanocomposites show a threefold higher intracellular delivery of nanoparticles in various cells including primary lung epithelial cells, macrophages, and a 10-fold increase in endothelial cells compared to naked PLGA nanoparticles or a twofold increase compared to nanoparticles modified with traditional monomeric CPPs. Cell uptake studies suggest that nanocomposites likely enter cells through mixed macropinocytosis and passive energy-independent mechanisms, which is followed by endosomal escape within 24 h. Nanocomposites also showed potent mucus permeation. More importantly, freeze-drying and nebulizing formulated nanocomposite powder did not affect their physiochemical and biological activity, which further highlights the translative potential for use as a stable drug carrier for pulmonary drug delivery. We expect nanocomposites based on peptide nanofibers, and PLGA nanoparticles can be custom designed to encapsulate and deliver a wide range of therapeutics including nucleic acids, proteins, and small-molecule drugs when employed in inhalable systems to treat various pulmonary diseases.

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“…As aforementioned, biopolymer PEMCs are attractive in terms of their potential to mimic the extracellular matrix (ECM) as well as host bioactive molecules. Single-and multi-domain peptides (SDPs and MDPs, respectively) are emerging as materials for use in tissue engineering/regeneration applications within the development of nanofibrous scaffolds [258,259]. The incorporation of these bioactive-mimicking SDP/MDPs into PEMCs are of interest.…”

Section: Functionalisation With Ligands and Antibodiesmentioning

confidence: 99%

Biopolymer-Based Multilayer Capsules and Beads Made via Templating: Advantages, Hurdles and Perspectives

Vikulina

Campbell

2021

Nanomaterials

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One of the undeniable trends in modern bioengineering and nanotechnology is the use of various biomolecules, primarily of a polymeric nature, for the design and formulation of novel functional materials for controlled and targeted drug delivery, bioimaging and theranostics, tissue engineering, and other bioapplications. Biocompatibility, biodegradability, the possibility of replicating natural cellular microenvironments, and the minimal toxicity typical of biogenic polymers are features that have secured a growing interest in them as the building blocks for biomaterials of the fourth generation. Many recent studies showed the promise of the hard-templating approach for the fabrication of nano- and microparticles utilizing biopolymers. This review covers these studies, bringing together up-to-date knowledge on biopolymer-based multilayer capsules and beads, critically assessing the progress made in this field of research, and outlining the current challenges and perspectives of these architectures. According to the classification of the templates, the review sequentially considers biopolymer structures templated on non-porous particles, porous particles, and crystal drugs. Opportunities for the functionalization of biopolymer-based capsules to tailor them toward specific bioapplications is highlighted in a separate section.

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Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers

Abstract: In this work, we demonstrated a facile supramolecular approach based on modularly designed multi-domain peptides to construct peptide-based nanomaterials with intrinsic cell penetrating activity and excellent cytocompatibility.

Cited by 8 publications

References 50 publications

Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery

Biopolymer-Based Multilayer Capsules and Beads Made via Templating: Advantages, Hurdles and Perspectives

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