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Cell penetrating peptides (CPPs) are usually positive charged peptides and have good cell membrane permeability. Meanwhile, CPPs are facile to synthesize, and can be functionalized to satisfy different demands, such as cyclization, incorporating unnatural amino acids, and lipid conjugation. These properties have made them as efficient drug-delivery tools to deliver therapeutic molecules to cells and tissues in a nontoxic manner, including small molecules, DNA, siRNA, therapeutic proteins and other various nanoparticles. However, the poor serum stability and low tumor targeting ability also hindered their broad application. Besides, inappropriate chemical modification can lead to membrane disruption and nonspecific toxicity. In this paper, we first reviewed recent advances in the CPP applications for cancer therapy via covalent or non-covalent manners. We carefully analyzed the advantages and disadvantages of each CPP modifications for drug delivery. Then, we concluded the recent progress of their clinical trials for different diseases. Finally, we discussed the challenges and opportunities CPPs met to translate into clinical applications. This review presented a new insight into CPPs for drug delivery, which could provide advice on the design of clinically effective systemic delivery systems using CPPs. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa. In addition, the current compounds have low selectivity for the pathogen, leading to various side effects, which results in lower adherence to treatment. Various strategies were developed to solve this problem. The bioconjugation between natural compounds with antimicrobial activity and cell-penetrating peptides could alleviate the resistance and toxicity of current treatments. This work aims to conjugate the cell penetration peptide TAT to the guanidine GVL1. The GVL1-TAT bioconjugate exhibited leishmanicidal activity against Leishmania amazonensis and Leishmania infantum with a high selectivity index. In addition, the bioconjugate was more active against the intracellular enzyme CPP than the individual compounds. This target is very important for the viability and virulence of the parasite within the host cell. Docking studies confirmed the higher interaction of the conjugate with CPP and suggested that other proteins, such as trypanothione reductase, could be targeted. Thus, the data indicated that guanidines conjugated with cell-penetrating peptides could be a good approach for developing antileishmanial molecules. [ABSTRACT FROM AUTHOR]

In the context of glioblastoma treatment, the penetration of drugs is drastically limited by the blood-brain-barrier (BBB). Emerging therapies have focused on the field of therapeutic peptides for their excellent BBB targeting properties that promote a deep tumor penetration. Peptide-based strategies are also renowned for their abilities of driving cargo such as liposomal system allowing an active targeting of receptors overexpressed on GBM cells. This review provides a detailed description of the internalization mechanisms of specific GBM homing and penetrating peptides as well as the latest in vitro / in vivo studies of liposomes functionalized with them. The purpose of this review is to summarize a selection of promising pre-clinical results that demonstrate the advantages of this nanosystem, including an increase of tumor cell targeting, triggering drug accumulation and thus a strong antitumor effect. Aware of the early stage of these studies, many challenges need to be overcome to promote peptide-directed liposome at clinical level. In particular, the lack of suitable production, the difficulty to characterize the nanosystem and therapeutic competition leaded by antibodies. [Display omitted] • Peptide-based approach as promissing agent for targeting glioblastoma receptors • Peptides attached to liposomes surface enhanced the blood-brain barrier crossing. • Liposomes functionalized with peptides increase drugs therapeutic index. • Peptides personalized therapy and nanosystem optimization remain challenges to overcome. [ABSTRACT FROM AUTHOR]

Cell penetrating peptides (CPPs) are usually positive charged peptides and have good cell membrane permeability. Meanwhile, CPPs are facile to synthesize, and can be functionalized to satisfy different demands, such as cyclization, incorporating unnatural amino acids, and lipid conjugation. These properties have made them as efficient drug-delivery tools to deliver therapeutic molecules to cells and tissues in a nontoxic manner, including small molecules, DNA, siRNA, therapeutic proteins and other various nanoparticles. However, the poor serum stability and low tumor targeting ability also hindered their broad application. Besides, inappropriate chemical modification can lead to membrane disruption and nonspecific toxicity. In this paper, we first reviewed recent advances in the CPP applications for cancer therapy via covalent or non-covalent manners. We carefully analyzed the advantages and disadvantages of each CPP modifications for drug delivery. Then, we concluded the recent progress of their clinical trials for different diseases. Finally, we discussed the challenges and opportunities CPPs met to translate into clinical applications. This review presented a new insight into CPPs for drug delivery, which could provide advice on the design of clinically effective systemic delivery systems using CPPs.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs) or antimicrobial peptides (AMPs), together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment, where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this study, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition. [ABSTRACT FROM AUTHOR]

Background: Reduced toxicity and ease of modification make gold nanoparticles (GNPs) suitable for targeted delivery and bioimaging via conjugating cell-penetrating peptides (CPPs). This study aimed to assess the enhanced penetration of gold nanoparticles into cells via using TAT peptide as a cell-penetrating peptide. Methods: Gold nanoparticles and TAT-conjugated gold nanoparticles (TAT-C-GNP) were characterized using ultraviolet-visible spectrophotometry, dynamic light scattering, zeta potential method, and transmission electron microscopy. The cytotoxicity effects of nanoparticles on HeLa, and A431 cell lines were studied. Uptake of TAT-conjugated gold nanoparticles was tested in cells, using dark field microscopy. Findings: Gold nanoparticles and TAT-conjugated gold nanoparticles had little to no effect on cell viability. Upon exposure to gold nanoparticles, TAT-conjugated gold nanoparticles displayed higher uptake than gold nanoparticles in A431 cell line; whereas none of the nanoparticles showed penetration in HeLa cell. Conclusion: Thus, TAT-conjugated gold nanoparticles have enhanced cellular internalization and are suitable for various biomedical applications as nanoconjugates.

Functionalization of gold nanoparticles (GNPs) is suitable for many applications such as biomedical imaging, clinical diagnosis, and targeted delivery by conjugating cell-penetrating peptides (CPPs). Here, we investigated intracellular uptake of GNP conjugated to MCaUF1-9(Ala), a CPP derived from maurocalcine (MCa) animal toxin, and compared it with TAT functionalized GNP. Peptide conjugated GNP was characterized using UV-Visible spectroscopy, dynamic light scattering, zeta potential, and transmission electron microscopy. Uptake of MCaUF1-9(Ala) and TAT functionalized GNPs was evaluated in three cell lines, HeLa, MDA-MB-231, and A431, using dark field imaging and atomic absorption spectroscopy. According to peptide sequences and type of cells different cell penetrating activity was observed. Peptide functionalized GNP had little effect on cell viability and respect to net charge difference between peptide, showed interesting selectivity against three cell types. Peptide conjugated to GNPs displayed higher uptake than bare GNPs in the all cell lines except HeLa cell with lowest internalization. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2693-2700, 2016. [ABSTRACT FROM AUTHOR]