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Updated: May 16, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Modulating active targeting nanoparticle design according to tumor progressions
Huifang Nie1, Rong Huang1, Guangwei Jiang1
1School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, Fudan University, Shanghai 201203, China.
Abstract:
Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.
Insights
This study reveals how nanoparticle size impacts cancer drug delivery. Smaller nanoparticles work best in early-stage tumors, while larger ones are more effective in advanced cancers due to specific receptor interactions.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Nanoparticle-based drug delivery systems show promise for cancer diagnosis and treatment.
- The influence of tumor progression on nanoparticle accumulation, particularly for active targeting nanoparticles, is not well understood.
Purpose of the Study:
- To investigate the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) of varying sizes in orthotopic breast cancer models with different tumor progressions.
- To elucidate the relationship between nanoparticle size, tumor progression, and targeting efficiency.
Main Methods:
- Utilized RGD-modified gold nanoparticles (AuNPs) of different sizes.
- Investigated nanoparticle accumulation and penetration in orthotopic breast cancer models at various stages of progression.
- Analyzed the effects of tumor extracellular matrix properties and receptor expression on nanoparticle behavior.
Main Results:
- Smaller active AuNPs demonstrated superior accumulation and penetration in early-stage tumors, attributed to favorable tumor microenvironment characteristics (looser matrix, larger gaps, lower pressure).
- Larger active AuNPs showed enhanced accumulation and penetration in late-stage tumors, driven by multivalent interactions with highly expressed integrin αvβ3 receptors.
- Mid-stage tumors exhibited accumulation influenced by both size effects and multivalent interactions, with 7 nm and 90 nm active AuNPs showing significant accumulation.
Conclusions:
- Nanoparticle size plays a critical role in optimizing accumulation and penetration in tumors, with the optimal size dependent on tumor progression.
- Understanding the interplay between nanoparticle size, tumor microenvironment, and target receptor expression is crucial for designing effective targeted cancer therapies.
- This research provides guidance for the rational design of active targeting nanoparticles to improve cancer diagnosis and treatment outcomes based on tumor progression.
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