Perspectives for Improving the Tumor Targeting of Nanomedicine via the EPR Effect in Clinical Tumors

Abstract

Over the past few decades, the enhanced permeability and retention (EPR) effect of nanomedicine has been a crucial phenomenon in targeted cancer therapy. Specifically, understanding the EPR effect has been a significant aspect of delivering anticancer agents efficiently to targeted tumors. Although the therapeutic effect has been demonstrated in experimental models using mouse xenografts, the clinical translation of the EPR effect of nanomedicine faces several challenges due to dense extracellular matrix (ECM), high interstitial fluid pressure (IFP) levels, and other factors that arise from tumor heterogeneity and complexity. Therefore, understanding the mechanism of the EPR effect of nanomedicine in clinics is essential to overcome the hurdles of the clinical translation of nanomedicine. This paper introduces the basic mechanism of the EPR effect of nanomedicine, the recently discussed challenges of the EPR effect of nanomedicine, and various strategies of recent nanomedicine to overcome the limitations expected from the patients’ tumor microenvironments.

Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements

“…Passive targeting primarily refers to the ability of nanoscale delivery systems to accumulate in tumor tissues through the EPR effect . These systems offer a range of advantages in drug delivery and treatment.…”

“…Passive targeting primarily refers to the ability of nanoscale delivery systems to accumulate in tumor tissues through the EPR effect. 107 These systems offer a range of advantages in drug delivery and treatment. A major benefit is improved bioavailability, as they can improve both the solubility and stability of drugs that are otherwise difficult to dissolve or unstable, expanding clinical applicability.…”

“…The enhanced permeability and retention (EPR) effect is a phenomenon wherein nanoparticles preferentially accumulate in tumor tissues due to their porous vasculature and impaired lymphatic drainage, which has been exploited to facilitate the passive targeting of anti-tumor agents. Through the EPR effect, drugs can be effectively delivered to tumor tissues, thereby enhancing therapeutic efficacy while reducing off-target side effects …”

“…The EPR effect varies among human tumors and sometimes shows poor vascular permeability, making it less reliable for effective drug delivery. Furthermore, drug accumulation depends largely on factors like circulation time and random extravasation into the tumor tissue in these systems, rather than targeted intracellular delivery, which can lead to inconsistent therapeutic outcomes, reduced bioavailability, and unintended off-target effects. , Given these limitations, active targeting systems have emerged by incorporating tumor-specific ligands like antibodies, peptides, and small molecules that bind to overexpressed receptors on cancer cells, allowing for receptor-mediated endocytosis, thereby increasing cell-specific internalization and intracellular uptake, which not only provides greater control over drug delivery but also offers the potential for reduced side effects, representing an important advancement over EPR-based passive targeting.…”

“…Through the EPR effect, drugs can be effectively delivered to tumor tissues, thereby enhancing therapeutic efficacy while reducing off-target side effects. 107 4.2.2. Early Nanoparticles Utilizing the EPR Effect for Camptothecin Delivery.…”