Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives

Sugimoto, Yuri; Suga, Tadaharu; Umino, Mizuki; Yamayoshi, Asako; Mukai, Hidefumi; Kawakami, Shigeru

doi:10.1080/10717544.2023.2191891

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…For both liposomes and LNPs a 2–3 fold increase in cytoplasmic fluorescence signal in A549 cells could be observed, in the case for the liposomes referred to a rhodamine dye and for the LNPs due to protein expression levels of the luciferase protein. In both cases the samples were compared to the nonfunctionalized particles and explained by the increased endosomal escape efficiency …”

Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

“…In both cases the samples were compared to the nonfunctionalized particles and explained by the increased endosomal escape efficiency. 42 However, none of these examples have completely eliminated off-targeting or dramatically increased the efficiency of delivery, which represent two major challenges for future nanomedicine.…”

Section: Surface-functionalized Lnpsmentioning

confidence: 99%

“…To overcome physiological and cellular barriers and/or to achieve successful targeting, a huge variety of nanoparticles have been functionalized with CPPs and CTPs, including liposomes, lipid nanoparticles (LNPs), polymeric nanoparticles, gold/metal nanoparticles, and silica quantum dots. − …”

Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

“…In both cases the samples were compared to the nonfunctionalized particles and explained by the increased endosomal escape efficiency. 42 …”

Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

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Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Aschmann,

Knol,

Kros

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: For the delivery of drugs, different nanosized drug carriers (e.g., liposomes, lipid nanoparticles, and micelles) have been developed in order to treat diseases that afflict society. Frequently, these vehicles are formed by the self-assembly of small molecules to encapsulate the therapeutic cargo of interest. Over decades, nanoparticles have been optimized to make them more efficient and specific to fulfill tailor-made tasks, such as specific cell targeting or enhanced cellular uptake. In recent years, lipid-based nanoparticles in particular have taken center stage; however, off-targeting side effects and poor endosomal escape remain major challenges since therapies require high efficacy and acceptable toxicity.To overcome these issues, many different approaches have been explored to make drug delivery more specific, resulting in reduced side effects, to achieve an optimal therapeutic effect and a lower required dose. The fate of nanoparticles is largely dependent on size, shape, and surface charge. A common approach to designing drug carriers with targeting capability is surface modification. Different approaches to functionalize nanoparticles have been investigated since the attachment of targeting moieties plays a significant role in whether they can later interact with surface-exposed receptors of cells. To this end, various strategies have been used involving different classes of biomolecules, such as small molecules, nucleic acids, antibodies, aptamers, and peptides. Peptides in particular are often used since there are many receptors overexpressed in different specific cell types. Furthermore, peptides can be produced and modified at a low cost, enabling high therapeutic screening. Cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs) are frequently used for this purpose. Less studied in this context are fusogenic coiled-coil peptides.Lipid-based nanoparticles functionalized with these peptides are able to avoid the endolysosomal pathway; instead such particles can be taken up by membrane fusion, resulting in increased delivery of payload. Furthermore, they can be used for targeting cells/organs but are not directed at surface-exposed receptors. Instead, they recognize complementary peptide sequences, facilitating their uptake into cells.In this Account, we will discuss peptides as moieties for enhanced cytosolic delivery, targeted uptake, and how they can be attached to lipid-based nanoparticles to alter their properties. We will discuss the properties imparted to the particles by peptides, surface modification approaches, and recent examples showing the power of peptides for in vitro and in vivo drug delivery. The main focus will be on the functionalization of lipid-based nanoparticles by fusogenic coiled-coil peptides, highlighting the relevance of this concept for the development of future therapeutics.

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Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

Section: Surface-functionalized Lnpsmentioning

confidence: 99%

Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

“…In both cases the samples were compared to the nonfunctionalized particles and explained by the increased endosomal escape efficiency. 42 …”

Section: Lipid-based Nanoparticles Functionalized With Cppsmentioning

confidence: 99%

See 2 more Smart Citations

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Aschmann,

Knol,

Kros

2024

Acc. Chem. Res.

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“…[ 17 , 26 , 30 , 31 , 32 , 33 ] Furthermore, the degradation products consist of naturally occurring amino acids that can undergo metabolic processes within the natural protein metabolic pathway. Although poly(EK) has been applied for surface coatings, [ 26 , 34 ] protein conjugation, [ 35 , 36 ] and drug delivery, [ 37 , 38 , 39 ] the study of poly(EK) hydrogels remains scarce due to the difficulties associated with the synthesis of the alternating polypeptides. Despite there having been attempts to develop EK hydrogels, the process has relied on N‐carboxyanhydride (NCA) ring‐opening random polymerization, resulting in hydrogels lacking a precisely defined zwitterionic alternating structure.…”

Section: Introductionmentioning

confidence: 99%

Poly(Glutamic Acid‐Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non‐Human Primates

Zhou,

Cao,

Chen

et al. 2024

Advanced Science

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The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti‐FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non‐human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long‐term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

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Additional Gene Therapeutic Platforms

Langel

2023

CPP, Cell-Penetrating Peptides

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Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives

Cited by 7 publications

References 41 publications

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Poly(Glutamic Acid‐Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non‐Human Primates

Additional Gene Therapeutic Platforms

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