ArticleLiterature Review

Multifaceted Roles of Pollen in the Management of Cancer

Authors:
  • National Institute for Pharmaceutical Education and Research hyderabad
  • National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad
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Abstract

Oral drug delivery of microparticles demonstrates shortcomings like aggregation, decreased loading capacity and batch-to-batch variation, which limits its scale-up. Later, porous structures gained attention because of their large surface-to-volume ratio, high loading capacity and ability to carry biomacromolecules, which undergo degradation in GIT. But there are pitfalls like non-uniform particle size distribution, the impact of porogen properties, and harsh chemicals. To circumvent these drawbacks, natural carriers like pollen are explored in drug delivery, which withstands harsh environments. This property helps to subdue the acid-sensitive drug in GIT. It shows uniform particle size distribution within the species. On the other side, they contain phytoconstituents like flavonoids and polysaccharides, which possess various pharmacological applications. Therefore, pollen has the capability as a carrier system and therapeutic agent. This review focuses on pollen's microstructure, composition and utility in cancer management. The extraction strategies, characterisation techniques and chemical structure of sporopollenin exine capsule, its use in the oral delivery of antineoplastic drugs, and emerging cancer treatments like photothermal therapy, immunotherapy and microrobots have been highlighted. We have mentioned a note on the anticancer activity of pollen extract. Further, we have summarised the regulatory perspective, bottlenecks and way forward associated with pollen.

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Traditional Chinese herbal medicine (TCHM) is the naturally available pharmaceutical with millennia of evolution from ancient China, capable of a superior therapeutic index and minimized unwanted effects on the human body. This work presents a therapeutic microrobotic platform based on pollen typhae (PT), a typical type of TCHM, fabricated by coating porous PT microspheres with Fe3O4 nanoparticles (PT robots) via electrostatic adsorption. The PT robots exhibit effective and controllable motion in various biological media upon external magnetic control and, meanwhile, preserve the inherent hemostasis property of PT. The blood clotting capacity of PT robots is attributed to their stimulation of the endogenous blood coagulation pathway and platelets with increased counts, which could be further improved by their effective magnetic propulsion. The remote magnetic control also allows the manipulation of PT robots in mice stomach, inducing enhanced binding and prolonged retention of PT robots in stomach mucosa. Moreover, PT robots upon magnetic control show an enhanced hemostatic effect in treating the mice bearing acute gastric bleeding compared with other passive groups. This work offers a facile and feasible route to integrate TCHM with manmade micromachines possessing the innate curative features of TCHM. Such a design expanded the versatility of microrobots and can be generalized to vast types of TCHM for broader biomedical applications.
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Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies shows the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anticancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/ß-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.
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This study highlights the protective role developed by encapsulation of Diclofenac Sodium (DIC) into natural Lycopodium Clavatum spores (LCS) to reduce gastric ulcerations associated with DIC administration in stomach of rats. Microencapsulation of DIC into empty LCS extracted from their natural, raw spore species was explored for the first time. LCS were characterized before and after drug loading using light microscopy, SEM, FTIR, TGA and particle size analyses. Different microencapsulation techniques (passive diffusion, vacuum-assisted and a combined passive-vacuum), varying loading duration and drug amounts were evaluated. Gastro-ulcerogenic activity of DIC loaded LCS against plain DIC was evaluated in rats. FTIR and TGA confirmed successful DIC encapsulation within the internal cavities of LCS. SEM, light micrographs and particle size analysis showed that drug loaded spores retained well defined microstructures similar to raw spores, with uniform size distributions of 20–25 μm. Encapsulation efficiency of DIC loaded LCS by vacuum-assisted loading was the highest (50%) compared to other loading techniques. A biphasic release pattern was achieved for drug loaded spores, with an initial fast release up till 2 h followed by a sustain release for 24 h, in phosphate buffer (pH 6.8), while ≥80% of plain DIC was released within 1 h. DIC loaded LCS showed substantial stomach protective action from related gastric ulcerations associated with DIC. Hence, a simple, reproducible approach utilizing Lycopodium Clavatum spores as natural encapsulant for oral delivery was established, with uniform micro-size distribution.
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Adoptive T cell immunotherapy is a powerful strategy for clinical cancer treatment. As a critical step to generate clinical-grade T cell products for therapeutic applications, novel approaches for T cell activation and expansion attract increasing attention. Here, we develop hydrogel-integrated natural pollens as artificial antigen-presenting scaffolds for ex vivo T cell expansion. Black phosphorus is presented in the scaffolds that allow for NIR-triggered release of cytokines and antibodies for T cell activation. Besides, the distinctive spike structure and high surface area of pollens contribute to T cell cluster formation and enhance their local proliferation. After ex vivo expansion, the activated T cells exhibit robust antitumor activity. Therefore, these features demonstrate that the novel pollen-based antigen-presenting scaffolds are promising for therapeutic T cell preparation.
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Background : Herbal Nano Medicines (HNMs) are nano-sized medicine containing herbal drugs as extracts, enriched fractions or biomarker constituents. HNMs have certain advantages because of their increased bioavailability and reduced toxicities. There are very few literature reports that address the common challenges of herbal nanoformulations, such as selecting the type/class of nanoformulation for an extract or a phytochemical, selection and optimisation of preparation method and physicochemical parameters. Although researchers have shown more interest in this field in the last decade, there is still an urgent need for systematic analysis of HNMs. Purpose : This review aims to provide the recent advancement in various herbal nanomedicines like polymeric herbal nanoparticles, solid lipid nanoparticles, phytosomes, nano-micelles, self-nano emulsifying drug delivery system, nanofibers, liposomes, dendrimers, ethosomes, nanoemulsion, nanosuspension, and carbon nanotube; their evaluation parameters, challenges, and opportunities. Additionally, regulatory aspects and future perspectives of herbal nanomedicines are also being covered to some extent. Methods : The scientific data provided in this review article are retrieved by a thorough analysis of numerous research and review articles, textbooks, and patents searched using the electronic search tools like Sci-Finder, ScienceDirect, PubMed, Elsevier, Google Scholar, ACS, Medline Plus and Web of Science. Results : In this review, the authors suggested the suitability of nanoformulation for a particular type of extracts or enriched fraction of phytoconstituents based on their solubility and permeability profile (similar to the BCS class of drugs). This review focuses on different strategies for optimising preparation methods for various HNMs to ensure reproducibility in context with all the physicochemical parameters like particle size, surface area, zeta potential, polydispersity index, entrapment efficiency, drug loading, and drug release, along with the consistent therapeutic index. Conclusion : A combination of herbal medicine with nanotechnology can be an essential tool for the advancement of herbal medicine research with enhanced bioavailability and fewer toxicities. Despite the challenges related to traditional medicine's safe and effective use, there is huge scope for nanotechnology-based herbal medicines. Overall, it is well stabilized that herbal nanomedicines are safer, have higher bioavailability, and have enhanced therapeutic value than conventional herbal and synthetic drugs.
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Pollen is an excellent natural substance that plays an essential role in the reproduction of plants. In this review, we explain the structure, compositions, and characteristics of pollens. We consider pollen as a multifunctional tool that can be used in therapeutic/diagnostic systems. This microcapsule can be used in the forms of the hollow microcapsule, microgel, and composite, and also can be a tool for the synthesis of micro/nanostructures in various medical applications and used for the production of genetically modified plants that affect human health. In addition, we investigate the capability of this multifunctional tool in the immune system targeting that acts as an immunomodulator. In all applications and capabilities, we explain the potential of using nanostructures as parts of these systems and as auxiliary tools for promoting the applications of pollen. It is expected that soon, with the help of pollen-based therapeutic/diagnostic systems with the ability to immune system targeting, we will achieve effective and targeted therapeutic systems for the treatment of inflammatory and autoimmune diseases. In this paper, we suggest some ideas that may be a new step for future researches.
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In angiosperms, mature pollen is wrapped by a pollen wall, which is important for maintaining pollen structure and function. Pollen walls provide protection from various environmental stresses and preserve pollen germination and pollen tube growth. The pollen wall structure has been described since pollen ultrastructure investigations began in the 1960s. Pollen walls, which are the most intricate cell walls in plants, are composed of two layers: the exine layer and intine layer. Pollen wall formation is a complex process that occurs via a series of biological events that involve a large number of genes. In recent years, many reports have described the molecular mechanisms of pollen exine development. The formation process includes the development of the callose wall, the wavy morphology of primexine, the biosynthesis and transport of sporopollenin in the tapetum, and the deposition of the pollen coat. The formation mechanism of the intine layer is different from that of the exine layer. However, few studies have focused on the regulatory mechanisms of intine development. The primary component of the intine layer is pectin, which plays an essential role in the polar growth of pollen tubes. Demethylesterified pectin is mainly distributed in the shank region of the pollen tube, which can maintain the hardness of the pollen tube wall. Methylesterified pectin is mainly located in the top region, which is beneficial for improving the plasticity of the pollen tube top. In this review, we summarize the developmental process of the anther, pollen and pollen wall in Arabidopsis; furthermore, we describe the research progress on the pollen wall formation pattern and its molecular mechanisms in detail.
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There are multiple obstacles for the storage and digestion of orally administered bioactive macromolecules. This study developed a low-cost and sustained-release delivery system (sporopollenin exine capsules with zein/tannic acid modification) of proteins with excellent storage stability, and at the same time provided insights into the sustained-release mechanism through exploring the interaction between zein and tannic acid (TA). β-Galactosidase (β-Gal) was utilized as a model protein and loaded into sporopollenin exine capsules (SECs), which were then coated with the zein/TA system. Under the optimized zein/TA conditions, the zein/TA system showed better performance than the zein alone system in the sustained release of β-Gal, with the residual activity of about 70.26% after 24 h of simulated digestion. Evaluation of the storage stability demonstrated a β-Gal residual activity of nearly 90% for 28 days at 25 °C. Additionally, FTIR analysis demonstrated that the stability of the zein/TA system depends on both hydrogen bonding and certain covalent bonding through the Schiff-base reaction, and the sustained release is regulated by the bonding strength.
Article
Pollen grains of 92 Bougainvillea genotypes were examined using a light microscope (LM) and scanning electron microscope (SEM) to identify taxonomic characteristics and the relationship between pollen morphology and germination capacity. The shapes of fresh pollen grains of Bougainvillea genotypes are spheroidal to prolate-spheroidal or suboblate after infolding. The sexine of Bougainvillea pollen grains consists of columellae and a reticulate cristatum, with or without microechini. The distribution pattern of the tectum microechini is uniform on the pollen grains within each genotype, yet it is variable among the different genotypes. Pollen with a smooth reticulate cristatum was observed in the genotypes of B. peruviana, while pollen with muri covering the cristatum were found in the genotypes of B. glabra and B. spectabilis. The pollen grains of each Bougainvillea germplasm have a wide range of diameters. The mean diameter of the pollen grains of the diploid genotypes ranged from 22.2 to 32.1 μm, while that of the polyploid genotypes ranged from 26.7 to 40.4 μm. The germinated pollen grains were observed in the diploid and tetraploid genotypes, the pollen germination rate of which was commonly less than 20 %. The size of germinated pollen grains was significantly larger than that of the silent ones, which indicated that the nonuniform distribution of grain size is a key reason for the low germination capacity of Bougainvillea pollen.
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Palmitic acid-modified bovine serum albumin (PAB) was synthetized and found to own remarkable scavenger receptor-A (SR-A) targeting ability in vitro and in vivo, through which activated macrophages took up PAB nanoparticles (PAB NPs) 9.10 times more than bovine serum albumin nanoparticles (BSA NPs) and PAB NPs could delivery anti-inflammatory drugs celastrol (CLT) to inflamed tissues more effectively than BSA NPs. Compared with chondroitin sulfate modified BSA NPs targeting activated macrophages via CD44, PAB NPs show a more prominent targeting effect whether in vivo or in vitro. And PAB also demonstrated excellent biosafety compared to maleylated BSA, a known SR-A ligand that was lethal in our study. Furthermore, in adjuvant-induced arthritis rats, CLT-PAB NPs significantly improved disease pathology at a lower CLT dose with high safety, compared with CLT-BSA NPs. In addition, compared with the existing ligands with SR-A targeting due to strong electronegativity, the enhanced electronegativity and introduced PA are both important for the SR-A targeting effect of PAB. Therefore, PAB provides a novel direction for the treatment of rheumatoid arthritis and design of new ligands of SR-A.
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Protein-gold nanoparticle (AuNP) bioconjugates have many potential applications in nanomedicine. A thorough understanding of the interaction between the protein and AuNP is critical to engineering these functional bioconjugates with desirable properties. In this work, we investigate the role of free thiols presented by the protein on the stability of the protein-AuNP conjugate. Human serum albumin (HSA) was modified with 2-iminothiolane (Traut’s reagent) to introduce additional thiols onto the protein surface, and three variants of HSA were synthesized to present 1, 5, and 20 free thiols by controlling the molar excess of the chemical modifier. Protein exchange studies on AuNPs were conducted using these HSA species and an IgG antibody which exhibited 10 free thiols. Antibody-AuNP conjugates were synthesized, purified, and dispersed in solutions containing each of the HSA species. No protein exchange was detected with the HSA or modified HSA containing 5 thiols; however, 85% of the antibody was displaced on the AuNP surface by the extensively thiolated HSA presenting 20 free thiols. Furthermore, the impact of the protein adsorption sequence was probed in which each of the HSA species were pre-adsorbed onto the AuNP and dispersed in a solution of antibody. The antibody fully displaced the HSA with a single thiol from the AuNP within 3 h, required 24 h to completely displace the modified HSA containing 5 thiols, and was unable to displace the modified HSA containing 20 thiols. These results indicate that the number of Au-S interactions governs the binding interaction between the protein and AuNP. This work provides further insight into the protein-AuNP binding mechanism and identifies important design principles for engineered proteins to optimize bioconjugates.
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In recent years the use of natural antioxidants in foodstuffs and personal care products has become increasingly important for consumers and therefore manufacturers. In this work, sporopollenin exine capsules (SpECs), extracted from spores of the common club moss Lycopodium clavatum L, have been shown to protect an ω-3 oil from oxidation caused by natural light or accelerated oxidation with UV irradiation. The mechanism of action has been shown to be principally by free radical quenching as opposed to light shielding, supported by evidence of similarity in levels of protection when the ratio of SpECs to oil was 0.2 % w/v compared with 50 % w/w. The antioxidant effect is not materially altered by the extraction process from the raw material and is clearly an inherent property of the sporopollenin contained in the spores of L. clavatum due to the accessible phenolic groups on the surface on the SpECs. These results provide promising evidence that SpECs could be useful as a bio-sourced antioxidant for protecting ω-3 oils and related oxidation-prone molecules.
Chapter
Metallic nanoparticulates (MNPs) are metal particulate of nanodimensions (such as gold NPs, silver NPs, and iron oxide NPs) that have been attracting the scientist over a century in various fields and now widely exploited for drug delivery and diagnostic applications. These nanostructured materials can be synthesized, and their surface modified/functionalized with different functional groups allow them to conjugate with moieties like therapeutics, diagnostics, and ligands. The various physicochemical properties, advantages, disadvantages, as well as characteristics of the metal nanoparticles, are comprehensively discussed, and insight into the site-specific drug targeting strategies for the management of chronic disorders. This chapter provides the detailed information on the synthesis of MNPs by various methods and characterization, with main emphasis on gene and drug delivery perspectives along with toxicity apprehensions. Present chapter also deals with the interactions of tailored MNPs and biological cells, factors affecting the cellular uptake and the intracellular destiny of MNPs, and also degradation of MNPs and its impact on nanotoxicity based on various literatures.
Chapter
Palynology (Gr.palynos, dust) is the study of spores and pollen grains. Spores and pollen grains have a number of morphological and ultrastructural features. These palyno-logical features have provided a wealth of characters that have been important in inferring phylogenetic relationships of plants. In addition, the features of spores and pollen grains can often be used to identify a particular plant taxon. For this reason, palynological studies are used extensively to examine the fossil record, a field called paleo-palynology. The identity, density, and frequency of pollen grains at a particular stratigraphic level can give information as to the plant species present at that time and place. Paleo-palynolgical studies are thus used to determine plant community structure and to gauge, by extrapolation over time, shifts in climate.
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The sporopollenin exine capsules (SECs) have recently attracted the attention of biological applications. The stability of SECs in human fluids is important issue to develop the controllable methods for the drug delivery system. Here, we analyzed the human plasma-triggered degradation of three species of SECs, i.e., camellia (Camellia sinensis L.), cattail (Typha angustifolia L.), and dandelion (Taraxacum officinale L.), regarding the physical and chemical aspects. The field emission scanning electron microscopy (FESEM) images showed no significant changes in the surface morphology of the SECs as increasing incubation time in human plasma, but we observed the increase of the rupture ratio by dynamic image particle analysis (DIPA). Also, Fourier-transform infrared spectroscopy (FTIR) combined with principal component analysis (PCA) addressed the chemical degradation in a species-specific manner. Specifically, the OH groups of camellia SECs, COC groups of cattail SECs, and CO groups of dandelion SECs showed significant changes.