Targeting Nanocarriers with Anisamide: Fact or Artifact?

Abstract

Encapsulating chemotherapeutics in nanoparticles can reduce the side effects of intravenous administration and improve their antitumor efficacy. Additionally, surface decoration of the nanocarriers with tumor-targeting ligands may enhance their specificity for cancer cells overexpressing the corresponding ligand-binding counterpart. The focus here is on anisamide, a low-molecular-weight benzamide derivative used as a tumor-directing moiety in functionalized nanosystems, based on its alleged interaction with Sigma receptors. The scintigraphic agents that initially inspired the use of anisamide for tumor targeting are described, and the published anisamide-tethered nanocarrier formulations are reviewed, together with a critical overview of the ligand's tumor-targeting properties. Moreover, anisamide's putative but dubious cellular target, the Sigma-1 receptor, is discussed with regard to its subcellular localization and implications in cancer. Data from in vivo studies reveal that the effect of anisamide on the antitumor efficacy of the decorated nanosystems varies considerably among the published reports. Together with the evidence questioning the interaction of anisamide with the Sigma receptors, the variability of anisamide's effect on the tumor deposition and the antitumor efficacy of the decorated drug carriers calls into question the extent of the ligand's tumor-targeting effect. Further research is necessary to elucidate the ligand's utility in tumor targeting.

Active targeting of gold nanoparticles as cancer therapeutics

“…Anisamide is a synthetically produced small molecule derived from anisole, a naturally occurring molecule found in aniseed oil. 138 The use of anisamide highlights another advantage of small molecules -they can be easily modified through structureactivity relationship studies to optimise their binding towards a target and remove unnecessary complexities from molecules that are not involved in the binding to a receptor. As with folic acid, anisamide lacks conjugation sites, meaning the siRNA is attached through electrostatic interactions with a PEI coating on the gold core (Fig.…”

Engineering Smart Targeting Nanovesicles and Their Combination with Hydrogels for Controlled Drug Delivery

“…Many cancer cells overexpress folate receptors, which makes the small molecule folate a great candidate to direct the delivery of liposomes containing cancer therapeutics towards cancer cells [ 49 , 50 , 51 ]. The overexpression of sigma receptors in many cancer cell lines has paved the way for another small molecule ligand possessing a high binding affinity to these receptors: anisamide [ 52 , 53 , 54 ]. Banerjee et al, attached the anisamide moiety to liposomes and included a PEG spacer between them to improve the ligand targetability and stability, and to increase the circulation half-life [ 55 ].…”

Calcium phosphate-based nanosystems for advanced targeted nanomedicine

“…CaP NPs were also functionalized with anisamide [231][232][233], a benzamide derivative that interacts with the Sigma-1 receptor of neoplastic cells whose effectiveness as targeting molecule is a matter of debate [252]. However, some of the works in the literature affirm that anisamide efficiently acts as targeting agent toward human lung cancer cells NCI-H-460 [231,233], murine melanoma cells B16F10 [232] and human colon carcinoma cells HT29-luc [234] allowing CaP NPs to deliver siRNAs.…”