Drug Delivery Systems for Overcoming Physical Barriers in Cancer Therapy

The efficacy of cancer therapy largely depends on the ability of drugs to penetrate the tumor tissues. However, therapeutic outcomes are often limited by formidable physical barriers in the tumor microenvironment (TME), including the blood–brain barrier (BBB), vascular barriers, extracellular matrix (ECM), elevated interstitial fluid pressure (IFP), and solid stress (SS). These barriers collectively restrict drug penetration, reducing the treatment effectiveness. Drug delivery systems (DDSs) have emerged as promising strategies to enhance drug penetration and distribution within tumors by overcoming these physical barriers. This review provides an in-depth examination of the characteristics of TME physical barriers and their impact on therapy as well as DDSs designed to overcome these barriers and improve drug delivery efficiency. Additionally, we discuss nanomaterials that have successfully reached the market or clinical trial phase, highlighting their challenges and significance. Overall, this review aims to inform and inspire the development of more effective DDSs, guiding future research and clinical applications to optimize tumor penetration and therapeutic outcomes.