Peptide-targeted nanoparticles for tumor therapy
Valeria Sidorenko, Allan Tobi, Kazuki N. Sugahara, Tambet Teesalu
Abstract
Most chemotherapeutics distribute non-specifically throughout the body, resulting in off-target toxicities. Nanoparticle (NP) formulations provide a strategy to improve drug delivery by extending circulation time, protecting therapeutic agents from degradation, and enabling controlled release. However, delivering NPs effectively to solid tumors remains challenging due to the barriers within the tumor microenvironment. Tumor-homing peptides address this challenge by targeting specific molecular markers accessible in tumors. These peptides bind to receptors on the tumor vasculature, facilitating drug delivery with reduced off-target effects. Unlike physicochemical approaches, which focus on optimizing NP properties such as size and charge but often lack specificity, tumor-homing peptides exploit molecular differences between healthy and malignant tissues to enable targeted delivery. A subclass of these peptides, known as tumor-penetrating peptides, promotes NP extravasation and tissue penetration, allowing delivery to cell populations deep within the tumor parenchyma. This review examines the use of tumor-homing peptides for NP delivery, focusing on their role in improving tumor accumulation, overcoming microenvironmental barriers, and enhancing therapeutic outcomes.