Dual function of lectins — new perspectives in targeted photodynamic therapy

Abstract

Porphyrins and phthalocyanines are photosensitizers (PS) that are used in clinical imaging, detection of cancer cells and are particularly applied in photodynamic therapy (PDT). Many scientists have been focused on the design of different porphyrin compounds. However, similar to other anti-cancer agents, they cannot selectively recognize tumor tissues. Scientists are seeking new methods to overcome this problem and to find appropriate targeted delivery strategies. Plant lectins are especially suitable molecules for such targeting as they preferentially recognize specific antigens on the glycosylated cancer cells. This review will give more detailed information about the dual function of lectins and their interactions with PSs, which is a new perspective in targeted PDT. The implications and potential applications of such studies will also be discussed.

Jacalin-Curcumin Complex Sensitizes the Breast Cancer MDA-MB-231 Cell Line

“…In addition, several plant lectins also displayed specific binding with hydrophobic ligands. These interactions occur at binding sites distinct from the carbohydrate-binding ones [25].…”

“…All these data motivated us to study the jacalin-curcumin interaction about the potential application of lectin as a drug carrier to cancer cells. Drug-protein complexes are important for biological systems [22][23][24][25][26][27][28]. Studying the molecular basis of the curcumin-protein interactions is important in designing novel therapeutic systems or improving selective drug delivery.…”

Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3

“…Coumaryl 2-O-acetylated galactoside, that targets the Gal3 glycan recognition, can interfere with the Gal3-promoted sustained profibrotic cell signaling and scar formation [51] and we show that Au 3+ TPPS can bind this same site ( Figure 6A). Here, Au 3+ TPPS has the potential as a Gal3 inhibitor or as well as a photosensitizer in photodynamic therapy [38]. The 2nd docking site for Au 3+ TPPS is placed on a part of the Gal3 molecule that is not known to be directly involved in carbohydrate binding ( Figure 6B).…”

“…Lectins have been well studied for their non-covalent association with porphyrins and with photosensitizers in general (for a recent review see [38]), and crystal structures of concanavalin A [39], peanut agglutininin [40] and jacalin [41] plant lectins in complex with meso-tetrasulfonatophenylporphyrin (H(2)TPPS) show very convincing evidence of the attractiveness of their carbohydrate binding site for the porphyrin [39][40][41]. However, H(2)TPPS binds by intruding, overlapping or allosterically hindering the carbohydrate-binding sites of concanavalin A, peanut agglutininin and jacalin, respectively, therefore porphyrin binding might negatively interfere with the highly selective cancer-antigen targeting function of the plant lectins [38]. An earlier study demonstrated that zinc tetrasulfonatophenylporphyrin (Zn 2+ TTPS) binds Gal3 with high affinity (K d = 0.18 µM) [42], largely surpassing N-acetyllactosamine, that is generally considered to be a specific binder of Gal3, with reported affinities K d = 25 µM [43], 28 µM [44], 112 µM [45] and 118 µM [46].…”

Binding of a Soluble meso-Tetraarylporphyrin to Human Galectin-7 Induces Oligomerization and Modulates Its Pro-Apoptotic Activity

“…Emerging work also illuminates their importance in many other biological processes, including nucleic acid synthesis and processing, signal transduction, and protein degradation, among many other cellular functions . Their medical appeal and relevance as photosensitizers in cancer treatment have also been amply demonstrated, especially in tumor imaging and photodynamic therapy. − These properties could provide a means to use porphyrin binding and intrinsic physicochemical imaging attributes as GAL-7 markers in cancerous tissue progression. Here, we used a combination of cellular, nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and molecular docking experiments to specifically alter GAL-7 function and characterize the effect of porphyrin binding on its molecular architecture.…”