Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Abstract

Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research.

Complexity of the Nano-Bio Interface and the Tortuous Path of Metal Oxides in Biological Systems

“…Diverse types of surface modifications can induce membrane translocation of metal oxides including cell penetrating peptides. Cell penetrating peptides, including penetratin, Tat, sC18, VP22, and the poly-arginines, have been used successfully to deliver a variety of proteins, polypeptides, nucleic acids organic/inorganic particles into the cell [ 126 ]. Last, some neutral zwitterions seem to enter cells by passive diffusion, whereas cationic and anionic NPs were taken up by endocytic processes [ 127 ].…”

A Global Review on Short Peptides: Frontiers and Perspectives

“…Supramolecular nanotherapeutics have better stability and efficacy, which helps to overcome problems related to peptide poor biostability and short plasma half-life. Nanoparticles’ conjungtion with inter alia tumor-homing peptides is an attractive avenue for tumor-targeted therapy [ 136 , 137 ]. The advances in the synthesis of supra-molecular assemblies prompt the development of theranostics (which possess specific smart features, such as programmability, multifunctionality, sensitivity, precise selectivity, biosafety) and are promising agents for personalized, smart medicine [ 126 , 138 , 139 ].…”

Epigenetic editing: Dissecting chromatin function in context

“…The current focus is on the conjugation of different nanomaterials to improve their safety, cellular intake and specificity towards a designated cell type or tissue. [ 165 ] In addition, new tools are being developed for epigenome therapy. For example, extracellular vesicles offer a promising cargo system for targeted delivery of epigenome editing molecules.…”