In cancer therapy, chemotherapeutic drugs frequently encounter multidrug resistance (MDR) induced by the overexpression of drug transporters such as P-glycoprotein (P-gp). Herein, in order to overcome MDR and improve the effectiveness of chemotherapy, we developed a novel pH-sensitive charge-reversal and NO generation liposomal system by modifying a pH-sensitive polymer (PEG-PLL-DMA) on the surface of cationic liposomes for delivering a NO donor (DETA NONOate) and a chemotherapy drug (paclitaxel, PTX) into MDR cells. The proposed liposomal system (PTX/NO/DMA-L) exhibited a distinctive charge-reversal capacity, which was negatively charged under physiological conditions (pH 7.4) but could reverse to positive charge in a tumor microenvironment (pH 6.5) due to the cleavable amide linkages formed between PEG-PLL and DMA, leading to the improvement of cell uptake. Once arrived in the endosomes and lysosomes (pH 5.0), DETA NONOate was triggered to decompose and release NO, which further promoted the quick release of PTX and inhibited the P-gp mediated efflux. The charge-reversal, NO generation and NO-triggered rapid release of drugs could significantly increase the accumulation of PTX in tumors and eventually improve the antitumor efficacy. These results indicate that this dual pH-sensitive liposomal system is a highly promising approach for chemotherapy and may pave a new avenue for overcoming MDR in cancer.

A dual pH-sensitive liposomal system with charge-reversal and NO generation for overcoming multidrug resistance in cancer.

To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the mannose-binding site consists of a small, central, carbohydrate-binding pocket responsible for the "broad sugar-binding specificity" toward a single mannose molecule, surrounded by a more extended binding area responsible for the specific recognition of larger mannose-containing N-glycan chains. Accordingly, the mannose-binding specificity of the so-called mannose-binding lectins towards complex mannose-containing N-glycans depends largely on the topography of their mannose-binding site(s). This structure⁻function relationship introduces a high degree of specificity in the apparently homogeneous group of mannose-binding lectins, with respect to the specific recognition of high-mannose and complex N-glycans. Because of the high specificity towards mannose these lectins are valuable tools for deciphering and characterizing the complex mannose-containing glycans that decorate both normal and transformed cells, e.g., the altered high-mannose N-glycans that often occur at the surface of various cancer cells.

https://hal-amu.archives-ouvertes.fr/hal-02388775/document

Overview of the Structure–Function Relationships of Mannose-Specific Lectins from Plants, Algae and Fungi

Insights into anti-pathogenic activities of mannose lectins.

Lectins are widely distributed proteins having ability of binding selectively and reversibly with carbohydrates moieties and glycoconjugates. Although lectins have been reported from different biological sources, the legume lectins are the best-characterized family of plant lectins. Legume lectins are a large family of homologous proteins with considerable similarity in amino acid sequence and their tertiary structures. Despite having strong sequence conservation, these lectins show remarkable variability in carbohydrate specificity and quaternary structures. The ability of legume lectins in recognizing glycans and glycoconjugates on cells and other intracellular structures make them a valuable research tool in glycomic research. Due to variability in binding with glycans, glycoconjugates and multiple biological functions, legume lectins are the subject of intense research for their diverse application in different fields such as glycobiology, biomedical research and crop improvement. The present review specially focuses on structural and functional characteristics of legume lectins along with their potential areas of application.

Research advances and prospects of legume lectins

Pathogenic enveloped viruses are covered with a glycan shield that provides a dual function: the glycan structures contribute to virus protection as well as host cell recognition. The three classical types of N-glycans, in particular complex glycans, high-mannose glycans, and hybrid glycans, together with some O-glycans, participate in the glycan shield of the Ebola virus, influenza virus, human cytomegalovirus, herpes virus, human immunodeficiency virus, Lassa virus, and MERS-CoV, SARS-CoV, and SARS-CoV-2, which are responsible for respiratory syndromes. The glycans are linked to glycoproteins that occur as metastable prefusion glycoproteins on the surface of infectious virions such as gp120 of HIV, hemagglutinin of influenza, or spike proteins of beta-coronaviruses. Plant lectins with different carbohydrate-binding specificities and, especially, mannose-specific lectins from the Vicieae tribe, such as pea lectin and lentil lectin, can be used as glycan probes for targeting the glycan shield because of their specific interaction with the α1,6-fucosylated core Man3GlcNAc2, which predominantly occurs in complex and hybrid glycans. Other plant lectins with Neu5Ac specificity or GalNAc/T/Tn specificity can also serve as potential glycan probes for the often sialylated complex glycans and truncated O-glycans, respectively, which are abundantly distributed in the glycan shield of enveloped viruses. The biomedical and therapeutical potential of plant lectins as antiviral drugs is discussed.

https://www.mdpi.com/2073-4409/11/3/339/pdf?version=1643286259

Legume Lectins with Different Specificities as Potential Glycan Probes for Pathogenic Enveloped Viruses

Biochemical characterisation of lectin from Indian hyacinth plant bulbs with potential inhibitory action against human cancer cells

It is now established that metastable colloidal nanoparticles (NPs) are subjected to interactions with proteins in biological media leading to the formation of a protein corona on the NPs. The physiochemical and biological activity of the NPs is further determined by the bio–nano interface. However, in a realistic biosystem, multiple layers of interaction that the NPs may encounter even after protein coronation are generally overlooked. In the present study, carboxy and amine-functionalized CdSe quantum dots (QDs) were utilized as the primary NPs for protein corona formation using fetal calf serum. The quantitative and the qualitative aspects of the protein corona varying with respect to the surface functionalization of the QDs were analyzed. A second layer of complexity was added in the experimental setup by interacting the coronated-QDs with nanoplastics as a major pollutant source. The colloidal stability and the physiochemical parameters of the coronated-QDs in the presence of three differently functionalized polystyrene beads (plain, aminated, and carboxylated) were assessed using transmission electron microscopy, dynamic light scattering, and zeta-potential measurements. A complex interplay of interactive forces and direct bonding of amino acids with the benzene ring of the PS-beads led to the development of a coronated-QD–PS complex in the size range of 400 nm. To assess the overall protein leaching, the coronated-QD–PS complex was further subjected to different pH-triggers. Atomic absorption spectroscopy was used to analyze the combinatorial effect of the protein corona and the PS-beads on the Cd2+ ion release from the QDs. The novel approach of the study aims to include the complexities of a realistic reaction milieu wherein NP interactions are not just limited to proteins.

Exploring the interactions between protein coronated CdSe quantum dots and nanoplastics

A novel Entadin lectin was isolated, purified, and characterized from the seeds of Entada rheedii by ammonium sulfate precipitation, followed by lactose affinity chromatography. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the purified Entadin lectin appeared as a single band (monomeric in nature) with a molecular mass of approximately 20 kDa in both reducing and nonreducing conditions. Mass spectroscopic analysis confirms the molecular weight of Entadin lectin as 19,333 Da. Entadin lectin showed a highest titer value in agglutination against human blood group B red blood cells, and its hemagglutination activity was inhibited by lactose, cellobiose, and galactose. Periodic acid Schiff staining confirmed the glycoprotein nature of Entadin lectin with an approximately 5% carbohydrate content. This lectin is highly stable even after incubation at a wide range of temperatures (30-60 °C) and pHs (6-10). The antiproliferative effect of Entadin lectin against lung cancer cells A549 and cervical cancer cells HeLa showed IC50 values of 28 and 32 μg/mL, respectively, and no antiproliferative activity against normal cells was observed. Cell morphological studies revealed that Entadin lectin induced apoptosis in both A549 and HeLa cancer cells, which was confirmed by acridine orange/ethidium bromide and Hoechst (33258) nuclear counterstaining.

Biochemical Characterization of Lactose Binding Entadin Lectin from Entada rheedii Seeds with Cytotoxic Activity against Cancer Cell Lines.

Lectins are carbohydrate-binding proteins broadly used in various therapeutic and biomedical applications. The variable affinity of lectins towards variety of carbohydrates has raised attention for the biologist to explore functional aspects of lectins.  Lectins express specificity to simple carbohydrates for example mannose, lactose, sialic acid, complex glycan, and glycoproteins. Lectins are classified based on their sugar specificity and are used as a tool to study protein-carbohydrate interactions. Lectins are ubiquitous in nature and identified from all sources such as bacteria, fungi, algae, and animals. Plants are the most abundant source of lectins, and till now, more than three hundred lectins were characterized from plants. These are distributed to various parts of a plant according to their requirements and function. The physiological role of lectins in a plant is still not well understood. The overabundant presence of lectins in plant seeds and storage tissues indicated their role in plant development. Plant lectins shows a broad range of activities like antibacterial, antifungal, insecticidal, anticancerous, antileishmanial, antiviral, and anticoagulants. In this review, we aim to highlight the plant lectins classification and their application in various biological aspects.

Sanjay Naik

Papers

Biochemical characterisation of lectin from Indian hyacinth plant bulbs with potential inhibitory action against human cancer cells

Exploring the interactions between protein coronated CdSe quantum dots and nanoplastics

Biochemical Characterization of Lactose Binding Entadin Lectin from Entada rheedii Seeds with Cytotoxic Activity against Cancer Cell Lines.

APPLICATIONS OF PLANT LECTINS IN BIOTECHNOLOGY AND THERAPEUTICS: Plant lectins application