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

Bottens, Ryan A.; Yamada, Tohru

doi:10.3390/cancers14225546

Cited by 21 publications

(27 citation statements)

References 165 publications

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“…Especially in cancer, many examples of CPPs employed as therapeutic tools are present and some of them are involved in pre-clinical and clinical trials. [170,201,202] Despite the large amount of research and pre-and clinical studies carried out till now (Table 7), no CPPs or CPP/cargo formulations have been approved by EMA or FDA and several clinical trials have been unsuccessfully terminated. In fact, many issues may hamper translation of CPPs into clinics, even if many of them may be overcome in different ways.…”

Section: Clinical and Diagnostic Applications Involving Cppsmentioning

confidence: 99%

“…From their first discovery in late 80 s, [14,200] CPPs have evolved in their applications as potential clinical and diagnostics tools, till reaching clinical trials for different pathologies. Especially in cancer, many examples of CPPs employed as therapeutic tools are present and some of them are involved in pre‐clinical and clinical trials [170,201,202] . Despite the large amount of research and pre‐ and clinical studies carried out till now (Table 7), no CPPs or CPP/cargo formulations have been approved by EMA or FDA and several clinical trials have been unsuccessfully terminated.…”

Section: Clinical and Diagnostic Applications Involving Cppsmentioning

confidence: 99%

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Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

et al. 2023

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Cell‐penetrating peptides (CPPs) encompass a class of peptides that possess the remarkable ability to cross cell membranes and deliver various types of cargoes, including drugs, nucleic acids, and proteins, into cells. For this reason, CPPs are largely investigated in drug delivery applications in the context of many diseases, such as cancer, diabetes, and genetic disorders. While sharing this functionality and some common structural features, such as a high content of positively charged amino acids, CPPs represent an extremely diverse group of elements, which can differentiate under many aspects. In this review, we summarize the most common characteristics of CPPs, introduce their main distinctive features, mechanistic aspects that drive their function, and outline the most widely used techniques for their structural and functional studies. We highlight current gaps and future perspectives in this field, which have the potential to significantly impact the future field of drug delivery and therapeutics.

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Section: Clinical and Diagnostic Applications Involving Cppsmentioning

confidence: 99%

Section: Clinical and Diagnostic Applications Involving Cppsmentioning

confidence: 99%

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

et al. 2023

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“…From this aspect, F I G U R E 8 Targeting organelle using cell-penetrating peptide (CPPs). The figure was reprinted from (Bottens & Yamada, 2022) with the permission of MDPI.…”

Section: Recent Advances In Predictingmentioning

confidence: 99%

“…The next stage of CPP‐based development of targeting cancer cells is linked with intracellular targeting using some amino acid sequences that support the localization of drug means in organelles. A recent review by Bottens and Yamada highlights intracellular targeted delivery of anticancer agents using CPP (Bottens & Yamada, 2022). This approach requires designing and checking of already known sequences specific for organelles: mitochondria, endoplasmatic reticulum, nucleus, etc.…”

Section: Intracellular Targeting By Cppsmentioning

confidence: 99%

Cell penetrating peptides: Highlighting points in cancer therapy

Asrorov

Wang

Zhang

et al. 2023

Drug Development Research

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Cell‐penetrating peptides (CPPs), first identified in HIV a few decades ago, deserved great attention in the last two decades; especially to support the penetration of anticancer drug means. In the drug delivery discipline, they have been involved in various approaches from mixing with hydrophobic drugs to the use of genetically conjugated proteins. The early classification as cationic and amphipathic CPPs has been extended to a few more classes such as hydrophobic and cyclic CPPs so far. Developing potential sequences utilized almost all methods of modern science: choosing high‐efficiency peptides from natural protein sequences, sequence‐based comparison, amino acid substitution, obtaining chemical and/or genetic conjugations, in silico approaches, in vitro analysis, animal experiments, etc. The bottleneck effect in this discipline reveals the complications that modern science faces in drug delivery research. Most CPP‐based drug delivery systems (DDSs) efficiently inhibited tumor volume and weight in mice, but only in rare cases reduced their levels and continued further processes. The integration of chemical synthesis into the development of CPPs made a significant contribution and even reached the clinical stage as a diagnostic tool. But constrained efforts still face serious problems in overcoming biobarriers to reach further achievements. In this work, we reviewed the roles of CPPs in anticancer drug delivery, focusing on their amino acid composition and sequences. As the most suitable point, we relied on significant changes in tumor volume in mice resulting from CPPs. We provide a review of individual CPPs and/or their derivatives in a separate subsection.

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“…A slower elimination rate can be specifically helpful when using peptides for enhancing drug transport to increase their time inside the organism. Some studies have suggested that some CPPs have enhanced uptake efficacy and delivery efficiency than other similar treatments, such as nanoparticles, while presenting less cytotoxicity [26]. Indeed, several peptides have already entered Phase I, Phase II and even, Phase III clinical trials [2].…”

Section: In Silico Evaluation Of the Pk Properties Of Peptides P1-p4mentioning

confidence: 99%

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil, and Doxorubicin Using In Silico Approaches

Vale

Pereira

Santos

et al. 2022

IJMS

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Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the tumor site, therefore contributing to overcoming these problems and enhancing the efficacy of chemotherapy. The drug combination is another promising strategy to overcome the aforementioned problems since the combined drugs can synergize through interconnected biological processes and target different pathways simultaneously. Here, we hypothesized that different peptides (P1–P4) could be used to enhance the delivery of chemotherapeutic agents into three different cancer cells (HT-29, MCF-7, and PC-3). In silico studies were performed to simulate the pharmacokinetic (PK) parameters of each peptide and antineoplastic agent to help predict synergistic interactions in vitro. These simulations predicted peptides P2–P4 to have higher bioavailability and lower Tmax, as well as the chemotherapeutic agent 5-fluorouracil (5-FU) to have enhanced permeability properties over other antineoplastic agents, with P3 having prominent accumulation in the colon. In vitro studies were then performed to evaluate the combination of each peptide with the chemotherapeutic agents as well as to assess the nature of drug interactions through the quantification of the Combination Index (CI). Our findings in MCF-7 and PC-3 cancer cells demonstrated that the combination of these peptides with paclitaxel (PTX) and doxorubicin (DOXO), respectively, is not advantageous over a single treatment with the chemotherapeutic agent. In the case of HT-29 colorectal cancer cells, the combination of P2–P4 with 5-FU resulted in synergistic cytotoxic effects, as predicted by the in silico simulations. Taken together, these findings demonstrate that these CPP6-conjugates can be used as adjuvant agents to increase the delivery of 5-FU into HT-29 colorectal cancer cells. Moreover, these results support the use of in silico approaches for the prediction of the interaction between drugs in combination therapy for cancer.

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

Cited by 21 publications

References 165 publications

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

Cell penetrating peptides: Highlighting points in cancer therapy

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil, and Doxorubicin Using In Silico Approaches

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