Peptide-based strategies for enhanced cell uptake, transcellular transport, and circulation: Mechanisms and challenges

Komin, Alexander; Russell, Luisa M.; Searson, Peter C.

doi:10.1016/j.addr.2016.06.002

Cited by 151 publications

(87 citation statements)

References 138 publications

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“…Furthermore, peptides can incorporate a variety of useful structural and functional motifs, including protein fragments with similar secondary structure features as their parent domains, and high-affinity/high-specificity cell-binding motifs selected through phage display or other high-throughput technologies. Additional advantages of peptides as compared to proteins include ease of production (in bacterial or mammalian cells, or by using solid phase peptide synthesis), and stability during storage and handling under ambient conditions [18,19]. Given their unique properties and facile production, peptides have been widely explored for their capacity to help overcome the barriers for gene delivery (Figure 2), including cell penetration, endosomal escape, and organelle targeting [19].…”

Section: Peptides For Gene Deliverymentioning

confidence: 99%

Gene delivery by peptide-assisted transport

Thapa

Sullivan

2018

Current Opinion in Biomedical Engineering

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The diverse amino acid chemistries and secondary structures in peptides provide ‘minimalist’ mimics of motifs in proteins and offer many ideal properties for targeted delivery approaches. Several non-viral vectors (polymers and lipids) have been studied for their potential applications in gene delivery. However, non-specific uptake, lack of targeting, inability to escape endosomes, and inefficient nuclear delivery limit their application. Peptide-assisted trafficking of non-viral vectors can potentially overcome these biological barriers to improve gene delivery through targeted uptake using key cell-surface receptors (e.g., integrins, growth factor receptors, and G-protein coupled receptors); membrane disruption for endosomal escape; and nuclear importation. Furthermore, the capacity of peptides to regulate spatio-temporal control over gene delivery opens multi-faceted avenues for effective gene delivery in a variety of complex applications. Rigorous on-going in vitro and in vivo studies utilizing peptides for targeted and microenvironment-sensitive gene delivery could promote their widespread clinical usage.

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Section: Peptides For Gene Deliverymentioning

confidence: 99%

Gene delivery by peptide-assisted transport

Thapa

Sullivan

2018

Current Opinion in Biomedical Engineering

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“…The chemoselective strategies for the conjugation of natural and synthetic polymers on peptides highly vary and are reported [54–59]. The conjugation of the non-peptidic group can be performed during solid phase peptide synthesis on resin.…”

Section: Introductionmentioning

confidence: 99%

“…These strategies can be enriched with chemical ligation in solution [68]. Comprehensive reviews on this topic have been described from other groups [56–59] . In this review, we survey the recent progress in the use of peptide and peptide-conjugates for self-assembled nanostructures in medicine (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

199

155

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Peptides and peptide-conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self-assembled nanostructures based on peptides and peptide-conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self-assembly of various nanomaterials based on peptides and peptide-conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self-assembly. First, we present the self-assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. The studies where nanoassembly is driven by the interactions between the conjugates of peptide-conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine, and challenges and future perspective are presented.

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“…Numerous approaches such as peptide-modified drug delivery systems have been explored in the past decades [12,13]. One extensively studied method is to modify the protein with a cell-penetrating peptide (CPP).…”

Section: Discussionmentioning

confidence: 99%

“…In the past decades, various approaches such as cell-penetrating peptide-or antibody-based drug delivery systems have been explored vigorously [12,13]. The monoclonal anti-DNA autoantibody 3E10, or its antigen-binding fragment (Fab) or single-chain variable fragment (scFv), is able to penetrate cell membrane of living cells and can deliver a variety of proteins, including a large 305 kDa alkaline phosphatase-conjugated goat antibody, to the cytosol or nuclei [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease

Sun

Armstrong

et al. 2017

J Mol Med

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Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers Bcargo^proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95-and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95-and the 76 kDa forms but not the 150 kDa form.

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Peptide-based strategies for enhanced cell uptake, transcellular transport, and circulation: Mechanisms and challenges

Cited by 151 publications

References 138 publications

Gene delivery by peptide-assisted transport

Gene delivery by peptide-assisted transport

Self-assembling peptide-based building blocks in medical applications

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease

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