Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Yu, Xi; Gou, Xin; Wu, Peng; Han, Liang; Tian, Daofeng; Du, F.; Chen, Zeming; Liu, Fuyao; Deng, Gang; Chen, Ann T.; Ma, Chao; Li, Jun; Hashmi, Sara M.; Guo, Xing; Wang, Xiaolong; Zhao, Haitian; Liu, Xinran; Zhu, Xudong; Sheth, Kevin N; Chen, Qianxue; Fan, Louzhen; Zhou, Jiangbing

doi:10.1002/adma.201705383

Cited by 44 publications

(23 citation statements)

References 22 publications

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“…Using parental systems, these authors developed a new one, with higher antimicrobial activity and pro-angiogenic properties in biological burn-wound bandages, named TNS18 (Siriwardena et al, 2018 ). Finally, other authors recently focused in self-assembling peptide nanoparticles that only act on the target cell after activation, using for that specific characteristics of the target tissue, such as overexpressed membrane proteins or enriched proteases concentration (Yu et al, 2018 ; Zhang et al, 2018 ). This field is now expanding and, therefore, more research is needed to understand how this strategy can benefit current therapies relative to other systems that are easier to manipulate.…”

Section: Nanoparticles In Therapeuticsmentioning

confidence: 99%

Application of Light Scattering Techniques to Nanoparticle Characterization and Development

et al. 2018

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Over the years, the scientific importance of nanoparticles for biomedical applications has increased. The high stability and biocompatibility, together with the low toxicity of the nanoparticles developed lead to their use as targeted drug delivery systems, bioimaging systems, and biosensors. The wide range of nanoparticles size, from 10 nm to 1 μm, as well as their optical properties, allow them to be studied using microscopy and spectroscopy techniques. In order to be effectively used, the physicochemical properties of nanoparticle formulations need to be taken into account, namely, particle size, surface charge distribution, surface derivatization and/or loading capacity, and related interactions. These properties need to be optimized considering the final nanoparticle intended biodistribution and target. In this review, we cover light scattering based techniques, namely dynamic light scattering and zeta-potential, used for the physicochemical characterization of nanoparticles. Dynamic light scattering is used to measure nanoparticles size, but also to evaluate their stability over time in suspension, at different pH and temperature conditions. Zeta-potential is used to characterize nanoparticles surface charge, obtaining information about their stability and surface interaction with other molecules. In this review, we focus on nanoparticle characterization and application in infection, cancer and cardiovascular diseases.

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Section: Nanoparticles In Therapeuticsmentioning

confidence: 99%

Application of Light Scattering Techniques to Nanoparticle Characterization and Development

et al. 2018

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“…Up to now, several peptides derived from coiled-coil regions have been tested, which have been described as antiviral, in particular to inhibit the entry of viruses such as HIV, HTLV, and SARS into cells. [48][49][50][51][52][53] Particularly peptides designed against HTLV-1 interfere with the association between coiled-coil domains of the core and consequently inhibit the activity of the viral particle.…”

Section: Discussionmentioning

confidence: 99%

An inhibitory mechanism of action of coiled‐coil peptides against type three secretion system from enteropathogenic Escherichia coli

Larzábal

Baldoni

Suvire

et al. 2019

Journal of Peptide Science

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Human pathogenic gram‐negative bacteria, such as enteropathogenic Escherichia coli (EPEC), rely on type III secretion systems (T3SS) to translocate virulence factors directly into host cells. The coiled‐coil domains present in the structural proteins of T3SS are conformed by amphipathic alpha‐helical structures that play an important role in the protein‐protein interaction and are essential for the assembly of the translocation complex. To investigate the inhibitory capacity of these domains on the T3SS of EPEC, we synthesized peptides between 7 and 34 amino acids based on the coiled‐coil domains of proteins that make up this secretion system. This analysis was performed through in vitro hemolysis assays by assessing the reduction of T3SS‐dependent red blood cell lysis in the presence of the synthesized peptides. After confirming its inhibitory capacity, we performed molecular modeling assays using combined techniques, docking‐molecular dynamic simulations, and quantum‐mechanic calculations of the various peptide‐protein complexes, to improve the affinity of the peptides to the target proteins selected from T3SS. These techniques allowed us to demonstrate that the peptides with greater inhibitory activity, directed against the coiled‐coil domain of the C‐terminal region of EspA, present favorable hydrophobic and hydrogen bond molecular interactions. Particularly, the hydrogen bond component is responsible for the stabilization of the peptide‐protein complex. This study demonstrates that compounds targeting T3SS from pathogenic bacteria can indeed inhibit bacterial infection by presenting a higher specificity than broad‐spectrum antibiotics. In turn, these peptides could be taken as initial structures to design and synthesize new compounds that mimic their inhibitory pharmacophoric pattern.

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“…For example, Sun and co-workers synthesized chitosan-stabilized BSA NPs with NEL-like molecule-1 protein (NELL-1) loading. [252] As shown in Figure 18a,b, three independent polypeptides consisting of functional peptides (Tat-NR2B9c: a neuroprotective peptide fused with CPP; melittin (Mel): a cytolytic peptide for treatment of stroke and cancer) self-assemble as activatable protein nanoparticles (APNPs). [245] In contrast to BSA/protein complex, the PEGylated BSA/protein complex micelle was more stable and had higher anticancer efficacy by inhibiting the growth of 3D MCF-7 multicellular tumor spheroids.…”

Section: Protein-based Complexmentioning

confidence: 99%

Rational Design of Nanocarriers for Intracellular Protein Delivery

et al. 2019

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Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein‐loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein‐based therapeutics is presented as well.

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Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides

Cited by 44 publications

References 22 publications

Application of Light Scattering Techniques to Nanoparticle Characterization and Development

Application of Light Scattering Techniques to Nanoparticle Characterization and Development

An inhibitory mechanism of action of coiled‐coil peptides against type three secretion system from enteropathogenic Escherichia coli

Rational Design of Nanocarriers for Intracellular Protein Delivery

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