Enhanced Permeability Drug Delivery Systems in Oncology
Summary
Enhanced permeability drug delivery systems exploit the intrinsic leakiness of tumour vasculature and impaired lymphatic drainage to concentrate therapeutic agents within malignant tissues. By employing nanoscale carriers—such as liposomes, polymeric micelles and antibody–drug conjugates—this strategy seeks to improve the therapeutic index of cytotoxic and photodynamic agents, minimising off-target toxicity. Central to this approach is the enhanced permeability and retention (EPR) effect, which arises from disordered angiogenesis and heterogeneous perfusion in solid tumours. While passive accumulation through the EPR effect has underpinned numerous preclinical successes, clinical translation remains challenged by inter-patient variability, stromal barriers and fluctuating vascular patency. Contemporary research focuses on refining carrier design, integrating stimuli-responsive linkers and combining vascular modulation or photoactivated interventions to augment permeability. Such advances aim to overcome tumour heterogeneity, achieve uniform distribution of payloads and pave the way for more effective, personalised oncological therapies.
Research from Nature Portfolio
Researchers have developed an antibody–drug conjugate that selectively binds insoluble fibrin within tumour stroma and releases its chemotherapeutic payload upon activation by plasmin. This approach overcomes uneven vascular permeability and improves intratumoural distribution of the drug, leading to enhanced accumulation and prolonged survival in preclinical models of stroma-rich cancers.
Enhanced Permeability Drug Delivery Systems in Oncology publication trend
The graph below shows the total number of articles in enhanced permeability drug delivery systems in oncology across all publications each year (not limited to Nature Index journals).
Technical terms
Enhanced permeability and retention (EPR) effect: Passive accumulation of macromolecular drugs and nanoparticles in tumour tissue due to leaky vasculature and poor lymphatic drainage.
Nanocarrier: A nanoscale vehicle such as liposomes, polymers or micelles designed to transport therapeutic agents preferentially to target tissues.
Antibody–drug conjugate (ADC): A bioconjugate linking a cytotoxic payload to a tumour-targeting antibody via a cleavable linker for selective drug release.
Super-enhanced permeability and retention (SUPR) effect: Transient, light-induced increase in vascular permeability after near-infrared photoimmunotherapy, markedly boosting nanoparticle delivery.
References
- Augmentation of EPR Effect and Efficacy of Anticancer Nanomedicine by Carbon Monoxide Generating Agents. Pharmaceutics (2019).
- Chemotherapy payload of anti-insoluble fibrin antibody-drug conjugate is released specifically upon binding to fibrin. Scientific Reports (2018).
- Enhanced nanodrug delivery in tumors after near-infrared photoimmunotherapy. Nanophotonics (2019).
- 35 years of discussions with Prof. Maeda on the EPR effect and future directions. Journal of Controlled Release (2022).
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