Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery

Abstract

Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.

Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study

“…This receptor is highly expressed in many human tumour cells including ovary, kidney, breast, myeloid, brain, and lung cancer cells [5]. Conjugation of a drug delivery system with folic acid (FA) has been used to achieve active targeting [6,7] as FA can be recognized by FRα with high binding constants (Kd ∼ 10 10 M −1 ) [5]. This has led to the development of various folate-appended drug carriers such as liposomes [8][9][10], dendrimers [11][12][13] and micelles [14][15][16].…”

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies

“…Therefore, the clinical development could be rapid for the drug delivery platforms that closely mimic the FDA-approved delivery systems. Secondly, clinical trials have been conducted on a few conjugates of FA and drugs (vinblastine and mitomycin C) using hydrophilic peptide spacers of varying lengths ( 131 ). The cancers included in these trials were small cell lung cancer, pituitary tumor, and OCs, however, the trial data have not yet been published.…”

Nanoarchitectonics: Complexes and Conjugates of Platinum Drugs with Silicon Containing Nanocarriers. An Overview

“…Targeted delivery of drugs called also active drug delivery exploits the presence of specific receptors on the surface of target cells, due to which it is possible to precisely deliver drugs to tumor cells and avoid systemic toxicity [78,79]. In this therapy, a number of targeting agents is applied with affinity for tumor cell receptors-the most widely used and inexpensive are folic acid, vitamin B 12 or biotin [80,81].…”