Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

https://www.mdpi.com/1420-3049/24/5/927/pdf

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies.

This review evaluates the literature on nanoparticle-based drug delivery systems for cancer treatment and assesses their efficacy. Nanoparticles have shown potential for improving anticancer agent delivery, reducing systemic toxicity, and enhancing therapeutic outcomes. Extensive studies have shown promising results in preclinical and clinical trials. However, challenges such as limited drug loading capacity, stability issues, and potential side effects need to be addressed to enhance clinical translation. Researchers are exploring strategies to improve drug loading capacity, such as modifying nanoparticle surfaces or developing novel drug encapsulation techniques. By increasing drug loading, the therapeutic efficacy of these systems can be significantly enhanced. Stability issues also pose a hurdle in clinical translation. To overcome stability issues, researchers are investigating methods to enhance the stability of nanoparticles, such as using protective coatings or optimising the formulation. Additionally, efforts are being made to minimise potential side effects by carefully selecting biocompatible materials for nanoparticle synthesis and conducting rigorous toxicity studies before moving forward with clinical trials. 

Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.

Polymeric Nanoparticles for Drug Delivery.

Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or “smart” NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.

Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue.

The application of repertoire selection technologies for the study and characterization of tumor heterogeneity is an area of great interest in the field of tumor biology and immunotherapy. Among the most promising approaches, phage display has been successfully used to select peptides and antibody fragments to a variety of different targets, including cancer cells, immune cells and cytokines. Peptides selected from phage display have been used to guide the delivery of lytic peptides, cytotoxic drugs, and nanoparticles to cancer cells with the aim to obtain more efficient and less toxic therapeutics. Additionally, antibodies developed through phage display are being used in the treatment of autoimmune diseases and in some cases metastatic cancers. This review provides a short description of how phage libraries are designed, and highlights the conversion of the isolated binders into human therapeutics and use in targeted therapies.

Phage Display Libraries: From Binders to Targeted Drug Delivery and Human Therapeutics

Preclinical Research Doxorubicin (DOX) is commonly used for the treatment of breast cancer and lymphoma. However, its clinical use has been severely limited due to cardiotoxicity, requiring the development of safer and more efficient pharmaceutical formulations of DOX. Advances in nanotechnology have provided new ways to administer chemotherapeutic drugs like DOX are conveyed into the body and to tumor sites. These Nanotechnology approaches have aided in the selective accumulation of DOX into tumor sites via the enhanced permeability and retention. However, the absence of active targeting ligands still hinders the effective delivery of DOX. Among all active targeting ligands developed to date, RGD peptide (Arginylglycylaspartic acid) occupies a unique position owing to its inherent safety, biocompatibility, and targeting ability. Accordingly, modification of DOX with RGD ligand is anticipated to improve transport of DOX into tumor cells. In this review, we discuss using RGD peptide for improving the therapeutic efficacy of DOX nanomedicine. Drug Dev Res 78 : 283-291, 2017. © 2017 Wiley Periodicals, Inc.

RGD Peptide-Based Target Drug Delivery of Doxorubicin Nanomedicine

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RGD Peptide-Based Target Drug Delivery of Doxorubicin Nanomedicine