An update on cell-penetrating peptides with intracellular organelle targeting

Cerrato, Carmine Pasquale; Langel, Ülo

doi:10.1080/17425247.2022.2034784

Cited by 29 publications

(24 citation statements)

References 106 publications

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“…Deleterious effects then predominate benefits. However, targeting sequences conjugated to CPP offer a precision medicine tool for acting on well-protected organelles [ 322 ], intracellular pathogens, hijacked processes in pathological conditions, and foreign molecules in our cells.…”

Section: Discussionmentioning

confidence: 99%

Designed Multifunctional Peptides for Intracellular Targets

Juretić

2022

Antibiotics

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Nature’s way for bioactive peptides is to provide them with several related functions and the ability to cooperate in performing their job. Natural cell-penetrating peptides (CPP), such as penetratins, inspired the design of multifunctional constructs with CPP ability. This review focuses on known and novel peptides that can easily reach intracellular targets with little or no toxicity to mammalian cells. All peptide candidates were evaluated and ranked according to the predictions of low toxicity to mammalian cells and broad-spectrum activity. The final set of the 20 best peptide candidates contains the peptides optimized for cell-penetrating, antimicrobial, anticancer, antiviral, antifungal, and anti-inflammatory activity. Their predicted features are intrinsic disorder and the ability to acquire an amphipathic structure upon contact with membranes or nucleic acids. In conclusion, the review argues for exploring wide-spectrum multifunctionality for novel nontoxic hybrids with cell-penetrating peptides.

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Section: Discussionmentioning

confidence: 99%

Designed Multifunctional Peptides for Intracellular Targets

Juretić

2022

Antibiotics

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“…Given that many genetic diseases originate from an error(s) in the genetic code, efforts are underway to target the nucleus more precisley. While the aforementioned HIV1 derivative, TAT, possesses an intrinsic ability to target the nucleus [ 89 ], better uptake rates can be achieved by combining the CPP with a nuclear-locating sequence. Interaction with the nucleus is achieved through the nuclear pore complex (NPC), which normally prohibits large molecules from entering the nucleus.…”

Section: Intracellular-targeted Delivery By Cppsmentioning

confidence: 99%

“…Using an NLS, which can assist the cargo molecule, induces active transport through the nuclear pore, where the administration of the desired drug can then be achieved. For example, an NLS derived from the Simian virus antigen (SV40) can be covalently bound to both a CPP such as TAT and a DNA-repairing cargo to attack the disease at its genetic source [ 89 ]. Another study showed that a conjugation between a viral gene vector, adenovirus, and CPP-PEG resulted in an uptake increase into the nucleus by nearly 80 times when compared to the adenovirus alone [ 90 ] The combination of specified nuclear targeting sequences with their respective CPP shows great potential in the ability to not only penetrate the normally impermeable nuclear membrane, but also efficiently administer drugs or gene editing molecules to tackle the disease at the source.…”

Section: Intracellular-targeted Delivery By Cppsmentioning

confidence: 99%

“…Another example of a specific MTS combination (MLRAALSTARRGPRLSRLL) was bound to H 3 R 8 , a CPP, and was successful in delivering 5-FAM dye into the mitochondria. The dye itself is normally impenetrable to the mitochondrial membrane and is delivered better than when compared to the MTS dye complex alone [ 89 ].…”

Section: Intracellular-targeted Delivery By Cppsmentioning

confidence: 99%

“…The folding of the endoplasmic reticulum (ER) is important to maximize the organelle’s surface area and volume to carry out the main ER functions which are protein folding and biosynthesizing lipids [ 89 ]. Since these functions are critical to biochemical pathways within the cell, disorders in the ER can lead to a myriad of diseases, including cancer.…”

Section: Intracellular-targeted Delivery By Cppsmentioning

confidence: 99%

See 2 more Smart Citations

Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer

Bottens

Yamada

2022

Cancers

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Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential for therapeutics and diagnostics for diseases such as cancer. Upon cellular entry, some CPPs have the ability to target specific organelles. CPP-based intracellular targeting strategies hold tremendous potential as they can improve efficacy and reduce toxicities and side effects. Further, recent clinical trials show a significant potential for future CPP-based cancer treatment. In this review, we summarize recent advances in CPPs based on systematic searches in PubMed, Embase, Web of Science, and Scopus databases until 30 September 2022. We highlight targeted delivery and explore the potential uses for CPPs as diagnostics, drug delivery, and intrinsic anti-cancer agents.

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Nuclear‐Targeting Peptides for Cancer Therapy

Yi,

Hussain,

Zhang

et al. 2024

ChemBioChem

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Nucleus is the central regulator of cells that controls cell proliferation, metabolism, and cell cycle, and is considered the most important organelle in cells. The precision medicine that can achieve nuclear targeting has achieved good therapeutic effects in anti‐tumor therapy. However, the presence of biological barriers such as cell membranes and nuclear membranes in cells limit the delivery of therapeutic agents to the nucleus. Therefore, developing effective nuclear‐targeting drug delivery strategies is particularly important. Nuclear‐targeting peptides are a class of functional peptides that can penetrate cell membranes and target the nucleus. They mainly recognize and bind to the nuclear transport molecules (such as Importin‐α/β) and transport the therapeutic agents to the nucleus through nuclear pore complexes (NPC). This review summarizes the most recent developments of strategies for anti‐tumor therapy utilizing nuclear‐targeting peptides, which will ultimately contribute to the development of more effective nuclear‐targeting strategies to achieve better anti‐tumor outcomes.

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An update on cell-penetrating peptides with intracellular organelle targeting

Cited by 29 publications

References 106 publications

Designed Multifunctional Peptides for Intracellular Targets

Designed Multifunctional Peptides for Intracellular Targets

Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer

Nuclear‐Targeting Peptides for Cancer Therapy

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