Nanotheranostics armed with folate: an integrated approach for precision targeting of glioblastoma

Glioblastoma (GBM) is extremely difficult to treat due to the poor blood-brain barrier (BBB) penetration, strong extracellular matrix, high interstitial pressure, and restricted cellular absorption, all of which prevent efficient drug delivery. Folate-conjugated nanotheranostics have emerged as a viable way to overcome these hurdles, taking advantage of GBM cells' upregulation of folate receptors (FRs). Folate-conjugation chemistry, either by direct ligand coupling or linker-assisted surface modification, have resulted in more selective receptor-based targeting, increased stability, and regulated chemotherapeutic release inside the tumor microenvironment. These nanosystems show increased penetration and selective absorption via FR-mediated endocytosis, which allows for deeper intratumoral distribution and more effective administration of chemotherapeutics and imaging agents. Recent advances in nanomedicine-based drug delivery systems with folate-functionalization shows promise for integrated GBM diagnosis and treatment. Latest findings also suggest good biocompatibility and low systemic toxicity of folate-armed nanotheranostics; however long-term safety is still a crucial issue and need to be discussed. This review summarizes the key challenges to GBM therapy and explores how folate-decorated nanotheranostics, via tailored chemistry and increased tumoral contact, constitute a potential option for GBM precision therapy.