An outlook on procedures of conjugating folate to (co)polymers and drugs for effective cancer targeting

Abstract

Folate receptors (FRs) are expressed in vast majority of cancers. Selective targeting of the FRs is, therefore, one of the most popular and sought‐after strategies for improving the efficacy of cancer therapeutics. Variety of approaches involving folate conjugation to several well‐known and novel, nontoxic, biodegradable, and biocompatible (co)polymers have been attempted and successfully applied to a large number of nanoparticulate drug delivery systems (micelles, liposomes, nanoparticles, quantum dots, mesoporous silica‐based materials, and others) in the last decade‐and‐a‐half. Standard and novel synthetic approaches were utilized for the conjugation, followed by the formulation of the drug delivery modality. In most of the cases, the targeted system lived up to its reputation, validating its usefulness in targeted cancer therapeutics. The present review summarizes the progress and state‐of‐the‐art synthetic methodologies for folate conjugation to (co)polymers, drugs, and nucleic acids. The limitations of the FR targeting are discussed in brief to give the reader the other side of the story. Finally, the information on marketed folic acid conjugates highlight their industrial applications.

Quantum dots as targeted doxorubicin drug delivery nanosystems in human lung cancer cells

“…In order to enhance their water solubility and thus biocompatibility, QDs can be coated with hydrophilic ligands (such as thiolate alcohols, thiolate acids and thiolate siloxane acids (Zhou et al 2017), or monothiol ligands including 3-mercaptopropionic acid (MPA) (Ali et al 2019) and mercaptoundecanoic (MUA)), amphiphilic polymers (such as polyethylene glycol (Susumu et al 2009), poly(N-isopropylacrylamide) (Hu and Gao 2010)), or silica (Cao et al 2020;Hu and Gao 2010). Besides these, glutathione (Aydemir et al 2020), bovine serum albumin (Barba-Vicente et al 2020;Sahoo et al 2019), poly(lactic-co-glycolic acids), and chitosan (Kharkar et al 2020) were also reported to promote the biocompatibility of QDs.…”

Design of Folate-Containing Liposomal Nucleic Acid Delivery Systems for Antitumor Therapy

“…The advantages of FA-mediated cancer cell targeting compared with other targeting ligands such antibodies or (poly)peptides include: (1) low immunogenicity allowing repeated administration; (2) rapid tumor penetration due to low molecular weight of FA conjugates; (3) high affinity to a wide range of tumors; (4) high stability allowing use of organic solvents, heating and prolonged storage time; (5) simple chemical structure providing cheap production and ease of quality control [ 22 , 23 , 24 ].…”

Folic acid and sodium folate salts: Thermal behavior and spectroscopic (IR, Raman, and solid-state 13C NMR) characterization

“…The sustained release of FA is also reported in innovative formulations in cosmetics [7,14]. In nanomedicine field, studies focused on harnessing the power of FA as a targeting agent for imaging and/or therapy (theragnosis) of cancer and inflammatory diseases [15][16][17][18]. The nanoengineering of smart delivery systems includes plenty of organic and inorganic nanoparticles as well as FA-drug conjugates [16][17][18].…”

“…In nanomedicine field, studies focused on harnessing the power of FA as a targeting agent for imaging and/or therapy (theragnosis) of cancer and inflammatory diseases [15][16][17][18]. The nanoengineering of smart delivery systems includes plenty of organic and inorganic nanoparticles as well as FA-drug conjugates [16][17][18]. In addition, FA forms complexes with a series of metal cations by coordination with its Glu or PT moieties [19][20][21][22][23][24].…”