Methods for CPP Functionalization

Langel, Ülo

doi:10.1007/978-981-13-8747-0_3

Cited by 2 publications

(3 citation statements)

References 405 publications

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“…Once the nanoparticles reach the colon, the ACS on their surface degrades, and the exposed CPP allows for the drug to penetrate the colonic epithelium. In vitro and in vivo evaluations indicate that these ACS-CPP nanoparticles may be a promising method for improving the oral absorption of proteins and peptides in a colon-specific manner (Langel, 2019) [144].…”

Section: Drug Conjugatesmentioning

confidence: 99%

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

Adebayo,

Agbaje,

Adesina

et al. 2023

Pharmaceutics

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Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university’s online library. The keywords were “Colorectal Cancer” AND “disease process” OR “disease mechanisms” OR “Current Treatment” OR “Prospects”. Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low–medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7–10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.

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Section: Drug Conjugatesmentioning

confidence: 99%

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

Adebayo,

Agbaje,

Adesina

et al. 2023

Pharmaceutics

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“…This exciting finding stimulated thoughts about the use of this dimeric amphipathic α-helical peptide and its derivatives as pharmaceutically relevant CPPs. In this regard, consideration was given to their toxicities at concentrations used for delivering modulator(s). , For systemic use as a CPP, both cell permeability (EC 50 ) and cytotoxicity (IC 50 ) should be considered to maximize cell permeability and minimize cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, consideration was given to their toxicities at concentrations used for delivering modulator(s). 6,7 For systemic use as a CPP, both cell permeability (EC 50 ) and cytotoxicity (IC 50 ) should be considered to maximize cell permeability and minimize cytotoxicity.…”

Section: ■ Introductionmentioning

confidence: 99%

Design and Optimization of an α-Helical Bundle Dimer Cell-Penetrating Peptide for In Vivo Drug Delivery

et al. 2022

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To deliver membrane-impermeable drugs into eukaryotic cells, a lot of cell-penetrating peptides (CPPs) were discovered. Previously we designed an amphipathic α-helical peptide which dimerizes itself via its two C-residues. This bis-disulfide-linked dimeric bundle, LK-3, has remarkable cell-penetrating ability at nanomolar concentration, which is an essential prerequisite for CPP. In an effort to optimize the sequence of LK-3, we adjusted its length and evaluated changes in the dimerization rate. We found that a 10-amino-acid monomer has the fastest dimerization rate and subsequently modified its hydrophobic and hydrophilic residues to construct a small peptide library. The evaluation of cell permeability of these derivatives showed that their cell-penetrating ability is comparable to that of the LK-3, except V- or H-containing ones. In this library, diLR10 was found to display fast nanomolar cell membrane penetration, low toxicity, and ease of production. The methotrexate (MTX) conjugate of diLR10, MTX-diLR10, has a 19-fold increased efficacy over MTX in MDA-MB-231 cells and efficiently deflates lesions in a rheumatoid arthritis (RA) in vivo mouse model.

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Methods for CPP Functionalization

Cited by 2 publications

References 405 publications

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

Design and Optimization of an α-Helical Bundle Dimer Cell-Penetrating Peptide for In Vivo Drug Delivery

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