Related Experiment Video
Updated: Jul 21, 2025
Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
Evaluation of Folate-Functionalized Nanoparticle Drug Delivery Systems-Effectiveness and Concerns
Muhammad Aiman Irfan Ibrahim1, Rozana Othman1,2, Chin Fei Chee3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Abstract:
Targeting folate receptors is a potential solution to low tumor selectivity concerning conventional chemotherapeutics. Apart from antibody-drug conjugates, folate-functionalized nanoparticle drug delivery systems are interesting to be explored due to many advantages, yet currently, none seems to enter the clinical trials. Multiple in vitro evidence is available to support its efficacy compared to the non-targeting carrier and free drug formulation. Additionally, several studies pointed out factors affecting its effectiveness, including surface properties and endosomal trapping. However, in vivo biodistribution studies revealed issues that may arise from folate receptor targeting, including rapid liver uptake, subsequently reducing the nanoparticles' tumor uptake. This issue may be due to the folate receptor β expressed by the activated macrophages in the liver; route of administration and tumor location might also influence the targeting effectiveness. Moreover, it is perplexing to generalize nanoparticles reported from various publications, primarily due to the different formulations, lack of characterization, and experimental settings, making it harder to determine the accurate factor influencing targeting effectiveness.
Insights
Folate-functionalized nanoparticles show promise for cancer drug delivery, but in vivo studies reveal challenges like liver uptake that limit tumor targeting effectiveness. Further research is needed to optimize these systems for clinical use.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Conventional chemotherapy often lacks tumor selectivity, leading to systemic toxicity.
- Folate receptors are overexpressed in various cancer cells, making them attractive targets for drug delivery.
- Folate-functionalized nanoparticles offer potential advantages over traditional drug delivery methods.
Purpose of the Study:
- To review the efficacy and challenges of folate-functionalized nanoparticle drug delivery systems.
- To identify factors influencing the in vivo performance of these targeted nanoparticles.
- To highlight the need for standardization in nanoparticle research for clinical translation.
Main Methods:
- Review of in vitro and in vivo studies on folate-targeted nanoparticles.
- Analysis of factors affecting nanoparticle efficacy, including surface properties and biodistribution.
- Examination of challenges hindering clinical translation, such as off-target organ accumulation.
Main Results:
- In vitro studies demonstrate the efficacy of folate-functionalized nanoparticles compared to non-targeted controls.
- In vivo studies show rapid liver uptake, potentially due to folate receptor beta expression on macrophages, reducing tumor accumulation.
- Variability in formulations, characterization, and experimental designs complicates generalization of findings.
Conclusions:
- Folate-targeted nanoparticles show preclinical promise but face in vivo challenges, notably liver uptake.
- Optimizing nanoparticle design and administration routes is crucial for improving tumor targeting.
- Standardized research methodologies are essential for advancing folate-functionalized nanoparticles toward clinical trials.
