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How Key in vivo Models Can Advance Anticancer Nanotherapeutics
Gudapureddy Radha1, B Devika Chithrani1,2
1Department of Physics and Astronomy, University of Victoria, Victoria, BC, V8P 5C2, Canada.
International Journal of Nanomedicine
|April 17, 2026
Summary
Nanoparticle properties influence drug delivery and cancer therapy, but biological interactions limit clinical use. Understanding how models affect nanoparticle performance is key for successful nanomedicine translation.
Area of Science:
- Nanomedicine
- Biomaterials Science
- Cancer Therapy
Background:
- Clinical translation of nanomedicine for cancer therapy is hindered by complex nanoparticle-biological system interactions.
- Nanoparticle physicochemical properties (size, shape, surface) critically influence cellular uptake, biodistribution, immune responses, and therapeutic efficacy.
- Current research integrates findings from various models to understand these interactions.
Purpose of the Study:
- To review and analyze how nanoparticle characteristics govern biological interactions and therapeutic performance across different experimental models.
- To identify model-dependent factors influencing nanoparticle behavior and translational outcomes in nanomedicine.
- To highlight the impact of biological systems, including the immune system and tumor microenvironment, on nanomedicine efficacy.
Main Methods:
- Comparative analysis of nanoparticle behavior in 2D cell cultures, 3D spheroids, xenograft, and immunocompetent tumor models.
- Integration of evidence on cellular uptake, processing, biodistribution, immune interactions, and therapeutic performance.
- Examination of physicochemical properties, biological barriers, and systemic factors affecting nanomedicine.
Main Results:
- 2D models reveal basic structure-function relationships for cellular interactions.
- 3D spheroids demonstrate the impact of matrix density and cell packing on nanoparticle transport.
- In vivo models, especially immunocompetent ones, highlight crucial roles of immune surveillance, protein corona, and tumor microenvironment heterogeneity in modulating nanoparticle fate and efficacy, often diminishing targeting benefits.
Conclusions:
- Successful nanomedicine design necessitates integrating material properties with a deep understanding of immune responses, vascular biology, and tumor microenvironment dynamics.
- Future nanomedicine development requires nanoparticles stable in immune-intact hosts, with reduced clearance and enhanced intratumoral delivery.
- Development of physiologically relevant predictive models is essential to bridge the gap between preclinical findings and clinical translation.
