Evaluation of Folate-Functionalized Nanoparticle Drug Delivery Systems-Effectiveness and Concerns

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 & beta; 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.

Automated summary

Targeting folate receptors is a potential solution for addressing low tumor selectivity in conventional chemotherapeutics. Folate-functionalized nanoparticle drug delivery systems show promise due to their advantages, although none have entered clinical trials. In vitro evidence supports their efficacy compared to non-targeting carriers and free drug formulations. However, in vivo biodistribution studies reveal issues with rapid liver uptake and reduced tumor uptake, potentially influenced by the expression of folate receptor β by activated macrophages in the liver, as well as the route of administration and tumor location. Generalizing nanoparticles reported in various publications is challenging due to different formulations, lack of characterization, and experimental settings, making it difficult to determine the accurate factors influencing targeting effectiveness.