Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy

We have developed a novel method for quantitation of lectin binding sites in mucins derived from colon tissues. Binding of peanut agglutinin and wheat germ agglutinin was measured in extracts from normal and malignant human colon epithelium. Binding of wheat germ agglutinin was used as an estimate of the total mucin present in the tissue extract. Peanut agglutinin was found to bind to mucin from normal colon, but at levels that may be difficult to appreciate by fluorescence microscopy. The yield of mucin extracted from colon cancer was more variable than that from normal colon, and the binding ratio of peanut agglutinin to wheat germ agglutinin was greater in extracts from tumors than in normal tissues. Our findings confirm the histological observation that peanut agglutinin binds more avidly to mucins from colon cancer than to those from normal colon. The finding of peanut agglutinin binding sites in mucins front normal colon was not expected. The quantitative technique may have detected small numbers of binding sites not readily appreciable by fluorescence microscopy. Alternatively, the chromatographic method for measuring lectin binding may be sufficiently sensitive to detect nonspecific binding of the lectin to terminal galactose residues other than the Thomsen-Friedenreich antigen.

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Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2010.08.023 ◽

2010 ◽

Vol 400 (1-2) ◽

pp. 201-210 ◽

Cited By ~ 45

Author(s):

Chunxia Wang ◽

Paul C. Ho ◽

Lee Yong Lim

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Wheat Germ Agglutinin ◽

Wheat Germ ◽

Intracellular Delivery ◽

Plga Nanoparticles ◽

Colon Cancer Cells

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Failure of 6D1 or Exposure of Platelets to ADP to Affect Agglutination Induced by Wheat Germ Agglutinin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646911 ◽

1989 ◽

Vol 62 (02) ◽

pp. 815 ◽

Cited By ~ 1

Author(s):

Marjorie B Zucker ◽

Robert A Grant ◽

Evelyn A Mauss

Keyword(s):

Wheat Germ Agglutinin ◽

Wheat Germ

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5-Fluorouracil Loaded Orally Administered WGA-decorated Poly(lactic-co-glycolic acid) Nanoparticles for Treatment of Colorectal Cancer: In Vivo Evaluation

Current Nanomedicine ◽

10.2174/2468187310999201123195233 ◽

2020 ◽

Vol 10 ◽

Author(s):

Aditya Nath Pandey ◽

Kuldeep Rajpoot ◽

Sunil K. Jain

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Oral Delivery ◽

Wheat Germ ◽

Glycolic Acid ◽

Organ Distribution ◽

In Vivo Evaluation ◽

Distribution Study ◽

Prolonged Retention

Background:: Several studies have suggested potential aptitude of polylactic-co-glycolic acid (PLGA)-derived nanoparticles (NPs) to improve the antitumor efficacy of anticancer drugs against colon cancer. Further, conjugation of lectins over the surface of the NPs may ameliorate interaction and thus enhance attachment of NPs with receptors. Objective:: The main goal of the study was to prepare and evaluate targeting potential (in vivo) of the optimized NPs against colorectal cancer. Methods:: The 5-fluorouracil (5-FU) loaded and wheat germ agglutinin (WGA)-conjugated PLGA-NPs (WFUNPs) were prepared and then they were evaluated in vivo for targeting aptitude of formulation using gamma scintigraphy after oral delivery. The WGA-conjugated and non-conjugated optimized NPs were compared for any significant results. Further, optimized formulations were also assessed for different parameters such as radiolabeling efficiency, sodium pertechnetate uptake, stability of NPs, and organ distribution study. Results:: Findings suggested prolonged retention of 99mTc-tagged WFUNPs in the colonic region after 24 h study. Eventually, the outcome from conjugated formulation revealed enhanced bioavailability of the drug in blood plasma for up to 24 h. Conclusion:: In conclusion, WGA-conjugation to NPs could improve the performance of the PLGA-NPs in the treatment of colorectal cancer.

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Transport Characteristics of Wheat Germ Agglutinin-Modified Insulin-Liposomes and Solid Lipid Nanoparticles in a Perfused Rat Intestinal Model

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.425 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2959-2966 ◽

Cited By ~ 16

Author(s):

Na Zhang ◽

Qineng Ping ◽

Guihua Huang ◽

Xiuzhen Han ◽

Yanna Cheng ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Wheat Germ Agglutinin ◽

Wheat Germ ◽

Serum Insulin ◽

Lipid Nanoparticles ◽

Solid Lipid ◽

Mucosal Absorption ◽

Perfusion Experiment ◽

Absorption Sites

Wheat germ agglutinin (WGA) modified liposomes and solid lipid nanoparticles (SLNs) were evaluated for improving intestinal absorption of insulin. In an in situ local intestinal perfusion experiment, formulations containing 100 IU/kg insulin were administered to the duodenum, jejunum, and ileum of fasted rats. As hypothesized, ileum was the best intestinal location for the absorption of insulin-containing liposomes. Serum insulin concentrations decreased for the various formulations in different absorption sites according to the following trends: Duodenum > ileum > jejunum for WGA-modified insulin-containing liposomes; duodenum > jejunum > ileum for WGA-modified insulin-containing SLNs; ileum > jejunum > duodenum for insulin-containing liposomes; ileum > duodenum > jejunum for insulin-containing SLNs; and duodenum ≥ ileum > jejunum for aqueous solution of insulin. These results imply that the nanoparticle type and delivery site were important factors with respect to increasing the bioavailability of insulin following oral administration. The proteolytic degradation as well as the epithelial permeability were primary determinants influcing insulin mucosal absorption.

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PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽

10.3390/cancers13092168 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2168

Author(s):

Balawant Kumar ◽

Rizwan Ahmad ◽

Swagat Sharma ◽

Saiprasad Gowrikumar ◽

Mark Primeaux ◽

...

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Side Population ◽

Therapy Resistance ◽

Fluorescent Reporter ◽

Combination Treatments ◽

Gsk 3Β ◽

Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

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Identification of distinct haemocyte populations from the freshwater bivalves swan mussel (Anodonta cygnea) and duck mussel (Anodonta anatina) using wheat-germ agglutinin

Canadian Journal of Zoology ◽

10.1139/cjz-2017-0006 ◽

2017 ◽

Vol 95 (12) ◽

pp. 937-947 ◽

Cited By ~ 3

Author(s):

M. Hinzmann ◽

M. Lopes-Lima ◽

F. Cerca ◽

A. Correia ◽

J. Machado ◽

...

Keyword(s):

Flow Cytometry ◽

Wheat Germ Agglutinin ◽

Wheat Germ ◽

Transmission Microscopy ◽

Anodonta Cygnea ◽

Functional Studies ◽

Lectin Staining ◽

Surface Staining ◽

Cytological Features ◽

Freshwater Bivalves

Haemocytes play a major role in molluscs immunity. Functional studies are, however, impaired by limited available experimental tools to identify and sort distinct haemocyte populations. Therefore, using nonlethal methods, we aimed at evaluating whether lectin staining combined with flow cytometry could be used to distinguish circulating haemocyte populations from two freshwater bivalves of the family Unionidae, the duck mussel (Anodonta anatina (L., 1758)) and the swan mussel (Anodonta cygnea (L., 1758)). Based on classical classification, haemocytes were distinguished as granulocytes and hyalinocytes and cytological features were visualized using transmission microscopy and staining techniques. Size, granularity, viability, and surface staining using lectins as specific probes were analysed by flow cytometry and fluorescence microscopy. The microscopic proportions of granulocytes and hyalinocytes significantly differed, being of 70% and 30% for A. cygnea and of 85% and 15% for A. anatina, respectively. Two haemocyte populations were sorted by flow cytometry based on size and granularity and confirmed as granulocytes and hyalinocytes. Interestingly, two different granulocyte populations could be further discriminated in A. cygnea according to their binding affinity to wheat-germ agglutinin (WGA), whereas granulocytes of A. anatina all stained similarly. Our results show that WGA labelling combined with flow cytometry can be used to better discriminate Anodonta haemocyte populations and obtain purified populations for functional studies.

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