Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides

Abstract

Active targeting of tumors is believed to be the key to efficient cancer therapy and accurate, early-stage diagnostics. Active targeting implies minimized off-targeting and associated cytotoxicity towards healthy tissue. One way to acquire active targeting is to employ conjugates of therapeutic agents with ligands known to bind receptors overexpressed onto cancer cells. The integrin receptor family has been studied as a target for cancer treatment for almost fifty years. However, systematic knowledge on their effects on cancer cells, is yet lacking, especially when utilized as an active targeting ligand for particulate formulations. Decoration with various integrin-targeting peptides has been reported to increase nanoparticle accumulation in tumors ≥ 3-fold when compared to passively targeted delivery. In recent years, many newly discovered or rationally designed integrin-binding peptides with excellent specificity towards a single integrin receptor have emerged. Here, we show a comprehensive analysis of previously unreviewed integrin-binding peptides, provide diverse modification routes for nanoparticle conjugation, and showcase the most notable examples of their use for tumor and metastases visualization and eradication to date, as well as possibilities for combined cancer therapies for a synergetic effect. This review aims to highlight the latest advancements in integrin-binding peptide development and is directed to aid transition to the development of novel nanoparticle-based theranostic agents for cancer therapy.

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…RGD is a peptide ligand targeting αvβ3 integrins which are overexpressed by tumor vessels and by a wide variety of human cancer cells. , It is therefore often used for tumor-targeting treatments. RGD was included in our recently developed peptide-porphyrin conjugate (PWG), which was shown to form pH-responsive nanoparticles capable of PDT.…”

Bridging Smart Nanosystems with Clinically Relevant Models and Advanced Imaging for Precision Drug Delivery

“…[ 99 ] Besides, the conjugation is conducted independently according to the various ligands and particle types, which could be influenced by environmental conditions. [ 100 ] Successful NP delivery systems necessitate meticulously designed ligands with strong binding capability and stability, which can be assessed for biocompatibility and toxicity through suitable in vitro and ex vivo human‐derived models. Moreover, demonstrating the adaptability and robustness of targeting strategies identified in vitro or ex vivo systems often requires in vivo animal experiments.…”

Nano-engineering nanomedicines with customized functions for tumor treatment applications

“…Receptor-mediated targeting is to specifically recognize receptors overexpressed on the surface of tumor cells by modifying targeted ligands on the surface of nanoparticles, thereby increasing the accumulation of nanoparticles at the tumor site [ 117 ]. The main receptors on the surface of tumor cells include folate receptor (FR) [ 118 , 119 ], transferrin receptor (TfR) [ 120 ], epidermal growth factor receptor (EGFR) [ 121 ], human epidermal growth factor receptor 2 (HER2) [ 122 ], Cluster of differentiation (CD) receptors-CD44 [ 123 ], αvβ3 integrin receptor [ 124 , 125 ], estrogen receptor (ER), biotin receptor, interleukin (IL) receptor, etc [ 126 ]. By modifying the ligands corresponding to the above receptors on the surface of nanomedicines, tumor cells can be specifically targeted and the accumulation of nanomedicines can be promoted, thereby improving the effect of tumor treatment.…”