Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Cell Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics

Version 1 : Received: 19 May 2021 / Approved: 21 May 2021 / Online: 21 May 2021 (09:44:48 CEST)

A peer-reviewed article of this Preprint also exists.

Stiltner, J.; McCandless, K.; Zahid, M. Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics. Pharmaceutics 2021, 13, 890. Stiltner, J.; McCandless, K.; Zahid, M. Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics. Pharmaceutics 2021, 13, 890.

Journal reference: Pharmaceutics 2021, 13, 890
DOI: 10.3390/pharmaceutics13060890

Abstract

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

Subject Areas

Cell penetrating peptides; protein transduction domains; tumor imaging; targeted therapies.

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