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

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.

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

“…Antibody and peptide conjugation of gold [ 267 ] and silica nanoparticles [ 268 ] have been thoroughly investigated for tumor targeting. In addition, inorganic nanoparticles are frequently modified with folic acid to target folate receptors commonly overexpressed in epithelial cancers [ 269 ].…”

Active-Targeting Biomimetic Polymer Nanoparticles for NIR Fluorescence Imaging and Enhanced Chemo-Sonodynamic Therapy of Cancer

“…Chemotherapy is a traditional malignant tumor cure method in clinical application . Most chemotherapeutic drugs are far from the targeting capacity at the tumor sites, and high dose administration is usually implemented to maintain the therapeutic drug concentration at the expense of serious side effect to normal tissue cells. , In addition, many nontargeting chemotherapeutic drugs enter the circulatory system blood and are cleared easily. − In this connection, a variety of nanocarriers, such as metal nanoparticles, polymeric nanoparticles, and polypeptide nanogels, were designed to improve the drug transportation ratio and reduce the clearance of drugs from the reticuloendothelial system. − Among them, Pluronic F-127 was the most widely used due to its excellent biocompatibility. For example, Zhang et al took advantage of Cas9 and chlorophyll-functionalized Pluronic F-127 micelles for effective A549 tumor therapy .…”