Engineered nanomedicines with enhanced tumor penetration

Nanomedicine has been extensively explored to enhance the efficacy of chemotherapy with modest therapeutic efficacy in the clinic, owing to various factors. A primary factor is inefficient tumor penetration caused by specific tumor microenvironments, such as insufficient blood supply, high-density tumor cells and extracellular matrix, and increased interstitial fluid pressure. To date, several strategies, including the modulation of tumor microenvironments and optimization of nanoparticle properties, have been reported to improve the tumor penetration of nanomedicines, but these traditional strategies still have limitations. Recently, with unique strategies like tumor-penetrating peptide-mediated transcellular transport, the multifunctional transformable nanoparticles have emerged as an advanced generation of nanomedicine with superior tumor penetration capabilities. In this review, the latest development and limitations of nanomedicines are summarized, and prospects for improving tumor penetration are discussed.