Liposomes as Multifunctional Nano-Carriers for Medicinal Natural Products

Cheng, Xiamin; Yan, Hui; Pang, Songhao; Ya, Mingjun; Qiu, Feng; Qin, Pin-Zhu; Zeng, Chao; Lu, Yongna

doi:10.3389/fchem.2022.963004

Cited by 27 publications

(25 citation statements)

References 156 publications

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“…However, various natural products usually have the limitations of low stability and solubility in the physiological environment and low delivery efficiency due to multi-targeting and low site-specific distribution in the lesion. Thus, drug delivery systems have been designed to improve those disadvantages, such as liposomes, inorganic metal frames, and hydrogels [ 93 , 94 , 95 ]. Computational modeling and computer-aided drug design have contributed immensely to the successful development of drugs, especially in the contemporary pharmaceutical and drug industries.…”

Section: Drugs That Target Glucose Metabolism Enzymesmentioning

confidence: 99%

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Zhang

Huang

et al. 2022

Cancers

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Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy.

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Section: Drugs That Target Glucose Metabolism Enzymesmentioning

confidence: 99%

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Zhang

Huang

et al. 2022

Cancers

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“…Because the GRs considered in our work are likely to be phagocytosed by multiple cells (endothelial cells, neurons, microglia, and astrocytes), we designed a methodology to specifically reach the macrophages in perivascular and meningeal locations. With respect to previous approaches based on diluted cargoes by luminal carrier liposomes non-specifically targeted under surface-adherent PEGylation ( Bunker et al, 2016 ; Cheng et al, 2022 ), the novel mannosylated GR@LNP nanovectors compactly charged toward phagocytic brain macrophages are strengthening therapeutic promise for the following reasons: 1) they specifically target the mannose receptor of BAMs; 2) their natural fate is phagocytosis; once internalized, they do not easily escape from the cell; 3) the intracellular release occurs along the endocytic pathway; once inserted in the BAM endocytic way, the lipid components are digested by lysosomal lipases; and 4) they accumulate in perinuclear proximity, favoring GR release into the ribosomes. Consequently, the compact GR-payload into cored @LNPs with a mannosylated corona assures optimal gene interference with respect to conventional liposomes under non-specific cell adherence and lighter loading.…”

Section: Discussionmentioning

confidence: 99%

Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages

Calero

Moleiro²,

Sayd³

et al. 2022

Front. Mol. Biosci.

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A colloidal synthesis’ proof-of-concept based on the Bligh–Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia. The GR@LNPs are expected to demonstrate a bio-orthogonal genetic activity reacting with L-PGDS gene transcripts inside the living system without interfering with other genetic or biochemical circuitries. To facilitate selective BAM phagocytosis and avoid subsidiary absorption by other cells, they were functionalized with a mannosylated lipid as a specific MAN ligand for the mannose receptor presented by the macrophage surface. The GR@LNPs showed a high GR-packing density in a compact multilamellar configuration as structurally characterized by light scattering, zeta potential, and transmission electronic microscopy. As a preliminary biological evaluation of the mannosylated GR@LNP nanovectors into specifically targeted BAMs, we detected in vivo gene interference after brain delivery by intracerebroventricular injection (ICV) in Wistar rats subjected to gene therapy protocol. The results pave the way towards novel gene therapy platforms for advanced treatment of neuroinflammation-related pathologies with ASO@LNP nanovectors.

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“…Liposomes are drug carriers with the advantages of low toxicity, high biocompatibility, and low immunogenicity, which can carry and contain various hydrophilic and lipophilic drugs (Yuba, 2020 ). Common liposomes are easily engulfed by the mononuclear phagocyte system after entering the blood as drug carriers, leading to their rapid clearance (Cheng et al., 2022 ). To overcome such problems, modification of liposomes (e.g.…”

Section: Pharmaceutical Designs Of Dhmmentioning

confidence: 99%

Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges

et al. 2022

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Dihydromyricetin (DHM) is an important natural flavonoid that has attracted much attention because of its various functions such as protecting the cardiovascular system and liver, treating cancer and neurodegenerative diseases, and anti-inflammation effect, etc. Despite its great development potential in pharmacy, DHM has some problems in pharmaceutical applications such as low solubility, permeability, and stability. To settle these issues, extensive research has been carried out on its physicochemical properties and dosage forms to produce all kinds of DHM preparations in the past ten years. In addition, the combined use of DHM with other drugs is a promising strategy to expand the application of DHM. However, although invention patents for DHM preparations have been issued in several countries, the current transformation of DHM research results into market products is insufficient. To date, there is still a lack of deep research into the pharmacokinetics, pharmacodynamics, toxicology, and action mechanism of DHM preparations. Besides, preparations for combined therapy of DHM with other drugs are scarcely reported, which necessitates the development of dosage forms for this application. Apart from medicine, the development of DHM in the food industry is also of great potential. Due to its multiple effects and excellent safety, DHM preparations can be developed for functional drinks and foods. Through this review, we hope to draw more attention to the development potential of DHM and the above challenges and provide valuable references for the research and development of other natural products with a similar structure-activity relationship to this drug.

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Liposomes as Multifunctional Nano-Carriers for Medicinal Natural Products

Cited by 27 publications

References 156 publications

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages

Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges

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