Conjugation of Paclitaxel to Hybrid Peptide Carrier and Biological Evaluation in Jurkat and A549 Cancer Cell Lines

Ayalew, Luladey; Acuna, Jessica; Urfano, Selina F.; Morfin, Cristobal; Sablan, Anthony; Oh, Myungeun; Gamboa, Alicia; Slowinska, Katarzyna

doi:10.1021/acsmedchemlett.7b00117

Cited by 31 publications

(20 citation statements)

References 22 publications

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“…Collagen can also act as a drug carrier or a drug targeted site. Hybrid collagen-cell penetrating peptide carriers improved resistance to enzymatic degradation [223]. Treating cancer with the single-chain fragment of cetuximab along with its collagen-binding domain demonstrated effective results [224].…”

Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

“…Collagen affinity can also be used to mediate targeted immunotherapy antibodies. Fusion of the collagen-binding protein lumican and cytokines increased the efficacy of systemic immunotherapies in a melanoma model [223]. The therapeutic use of immune checkpoint inhibitors and interleukin-2 by conjugation (for antibodies) or recombinant fusion (for cytokine) to the von Willebrand factor A3 domain (a collagen-binding domain) eradicated tumors and exhibited obvious safety and efficacy in a breast cancer model [225].…”

Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

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The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…Cell-penetrating peptides (CPPs) have been successfully used as vectors for efficient transportation of low bioavailable drugs into cells. 16 CPPs are a class of small peptides with a few to 30 amino acids that show membrane translocation activities. Because of their intrinsic ability to gain access to cell interiors, they have been successfully used for intracellular delivery of various membrane-impermeable bioactive agents.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Aqueous Solubility and Antibacterial Activity of Curcumin by Complexing with Cell-Penetrating Octaarginine

2020

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Bacterial resistance to antimicrobial drugs is one of the biggest threats to human health and novel drugs, and strategies are needed to obviate this resistance crisis. An innovative strategy for designing novel antimicrobial drugs is based on the hybridization of an antimicrobial agent with a second functional entity. Here, we use a cell-penetrating peptide–octaarginine (R8) as the second functional entity and develop a complex or hybrid of R8 and curcumin that possibly targets the bacterial cell membrane. Minimum inhibitory concentration assays show that the antibacterial activity of the complex is enhanced in a synergistic manner and rapid killing kinetics are obtained, emphasizing a bactericidal mode of action. In addition, electron microscopy images reveal bacterial membrane disruption by the complex. The R8–curcumin complex also displays activity against HeLa cells.

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“…We have recently demonstrated that many of these challenges can be resolved by introducing architectural motifs via synthetic linking of CPP with a collagen peptide 15,16 . This resulted in the formation of a triple helical nanocarrier that effectively delivered Paclitaxel to malignant cells 17 .…”

Section: Introductionmentioning

confidence: 99%

Higher Order Architecture of Designer Peptides Forms Bioinspired 10 nm siRNA Delivery System

Gamboa

Urfano

Hernandez

et al. 2019

Sci Rep

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The higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.

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Conjugation of Paclitaxel to Hybrid Peptide Carrier and Biological Evaluation in Jurkat and A549 Cancer Cell Lines

Cited by 31 publications

References 22 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

Enhancing Aqueous Solubility and Antibacterial Activity of Curcumin by Complexing with Cell-Penetrating Octaarginine

Higher Order Architecture of Designer Peptides Forms Bioinspired 10 nm siRNA Delivery System

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