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Updated: Jan 8, 2026
Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors
Published on: August 18, 2016
Analytical and computational chemistry approaches for mechanistic insights into nanoparticles tumor access
Qikai Wang1, Yanyan Liu2, Huan Meng1
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China; Sino-Danish College, Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, China.
Abstract:
Cancer nanotherapeutics has become one of the most advanced areas for basic and clinical research, yet a mechanistic consensus on how systemically administered nanoparticles (NPs) access tumors remains lacking. The enhanced permeability and retention (EPR) effect has long served as the classical paradigm to explain passive tumor accumulation, but its efficacy and clinical relevance have been increasingly questioned, especially in stroma-rich tumors. Emerging evidence, supported by high-resolution imaging technologies such as transmission electron microscopy (TEM) and intravital microscopy, reveals that transcytosis-represented non-EPR pathways play a dominant role in stroma-rich solid tumors. Understanding the mechanisms of these alternative entry routes is critical for the rational design of nanocarriers and their successful clinical translation. In this review, we outline the major pathways and characteristics of nanocarrier tumor access, summarize analytical and imaging strategies for probing nano/bio interactions in nanoparticle tumor entry, and highlight computational chemistry tools for high-throughput prediction of tumor access mechanisms. We further discuss future opportunities for integrating analytical and computational approaches to rationally design nanocarriers and guide personalized nanomedicine.
Insights
Nanoparticles (NPs) use transcytosis, not just the EPR effect, to enter tumors. Understanding these pathways is key for designing effective cancer nanomedicines.
Area of Science:
- Oncology
- Nanotechnology
- Biomedical Engineering
Background:
- Cancer nanotherapeutics is a rapidly advancing field.
- The enhanced permeability and retention (EPR) effect is the traditional explanation for nanoparticle tumor accumulation.
- The clinical relevance of the EPR effect is increasingly debated, particularly in stroma-rich tumors.
Purpose of the Study:
- To review the mechanisms of nanoparticle (NP) tumor entry.
- To highlight alternative, non-EPR pathways like transcytosis.
- To guide the rational design of nanocarriers for improved clinical translation.
Main Methods:
- Review of emerging evidence and high-resolution imaging techniques (e.g., TEM, intravital microscopy).
- Summary of analytical and imaging strategies for studying NP-tumor interactions.
- Highlighting computational chemistry tools for predicting tumor access mechanisms.
Main Results:
- Transcytosis and other non-EPR pathways are dominant in stroma-rich tumors.
- High-resolution imaging reveals NP interactions beyond the EPR effect.
- Computational tools offer high-throughput prediction of NP tumor entry.
Conclusions:
- Understanding non-EPR pathways is critical for nanocarrier design.
- Integrating analytical and computational approaches can optimize nanomedicine development.
- This knowledge facilitates personalized nanomedicine strategies.
