Investigating the intracellular effects of hyperbranched polycation–DNA complexes on lung cancer cells using LC-MS-based metabolite profiling

Alazzo, Ali; Al-Natour, Mohammad Ahmad; Spriggs, Keith A.; Stolnik, Snow; Ghaemmaghami, Amir M.; Kim, Dong-Hyun; Alexander, Cameron

doi:10.1039/c8mo00139a

Cited by 9 publications

(15 citation statements)

References 67 publications

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“…2). Six replicates were deemed to be valid for this type of cell linebased studies (Alazzo et al 2019;Surrati et al 2016). This separation indicated a distinctive metabolic signature of M1, M2 and M0 macrophages.…”

Section: Feature Selection and Identification Of Potential Biomarker mentioning

confidence: 99%

Metabolic characterisation of THP-1 macrophage polarisation using LC–MS-based metabolite profiling

et al. 2020

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Introduction Macrophages constitute a heterogeneous population of functionally distinct cells involved in several physiological and pathological processes. They display remarkable plasticity by changing their phenotype and function in response to environmental cues representing a spectrum of different functional phenotypes. The so-called M1 and M2 macrophages are often considered as representative of pro-and anti-inflammatory ends of such spectrum. Metabolomics approach is a powerful tool providing important chemical information about the cellular phenotype of living systems, and the changes in their metabolic pathways in response to various perturbations. Objectives This study aimed to characterise M1 and M2 phenotypes in THP-1 macrophages in order to identify characteristic metabolites of each polarisation state. Methods Herein, untargeted liquid chromatography (LC)-mass spectrometry (MS)-based metabolite profiling was applied to characterise the metabolic profile of M1-like and M2-like THP-1 macrophages. Results The results showed that M1 and M2 macrophages have distinct metabolic profiles. Sphingolipid and pyrimidine metabolism was significantly changed in M1 macrophages whereas arginine, proline, alanine, aspartate and glutamate metabolism was significantly altered in M2 macrophages. Conclusion This study represents successful application of LC-MS metabolomics approach to characterise M1 and M2 macrophages providing functional readouts that show unique metabolic signature for each phenotype. These data could contribute to a better understanding of M1 and M2 functional properties and could pave the way for developing new therapeutics targeting different immune diseases.

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Section: Feature Selection and Identification Of Potential Biomarker mentioning

confidence: 99%

Metabolic characterisation of THP-1 macrophage polarisation using LC–MS-based metabolite profiling

et al. 2020

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“…A correlation exists between toxicity and transfection efficiency (Alazzo et al, 2019) but this does not seem to be the case with sugar-functionalized PLL synergistic compounds (Han et al, 2018), which showed great affinity for loading siRNA, less cytotoxicity and maintained transfection efficiency as the original PLL modified by stearylamine. Surprisingly, it could even knock down some disease-related genes.…”

Section: Adjuvants Of Gene Therapymentioning

confidence: 97%

“…Meanwhile, as a dense group of distribution exists outside, LBD carriers protect the loaded ribonucleic acid from immune responses and nuclease degradation (Han et al, 2018). This non-viral system shows many advantages, including higher loading capacity, less inflammation potential, lower insertion mutagenic induction potential, cheaper scale, and easier functionalization, than the viral system (Walsh et al, 2018;Alazzo et al, 2019;Gorzkiewicz et al, 2020a). All these advantages make this non-viral system attract increasing attention.…”

Section: Adjuvants Of Gene Therapymentioning

confidence: 99%

“…The main mechanism of these phenomena has been demonstrated as inducing apoptosis in the beginning while being genotoxic with longer incubation (Gorzkiewicz et al, 2020a). In addition, cell metabolite analysis showed that hyperbranched polycation-DNA complexes made an alteration in energy metabolism and consequently influenced the redox homeostasis of cells (Alazzo et al, 2019).…”

Section: Adjuvants Of Gene Therapymentioning

confidence: 99%

“…In addition to the linear structure, another attractive structure of PLL belongs to the dendritic part. Since its first synthesis in 1985 (Tomalia et al, 1985), studies focusing on dendrimer structure have poured in, and this structure showed better properties than the linear forms in terms of transfection efficiency due to its higher cationic density, which may also simultaneously increase cytotoxicity (Alazzo et al, 2019). Dendritic materials composed of different compounds have expanded in recent years, including poly(amidoamine), polyetherimide, and LBD (Francoia et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Epsilon-Poly-L-Lysine and L-Lysine-Based Dendrimer Synthesis, Modification, and Biomedical Applications

Chen

Huang

et al. 2021

Front. Chem.

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With the advantages in biocompatibility, antimicrobial ability, and comparative facile synthesis technology, poly-L-lysine (PLL) has received considerable attention in recent years. Different arrangement forms and structures of the backbone endow lysine-based polymers with versatile applications, especially for ε-poly-L-lysine (EPL) and lysine-based dendrimer (LBD) compounds. This review summarized the advanced development of the synthesis and modification strategies of EPL and LBD, focus on the modification of bio-synthesis and artificial synthesis, respectively. Meanwhile, biomedical fields, where EPL and LBD are mainly utilized, such as agents, adjuvants, or carriers to anti-pathogen or used in tumor or gene therapies, are also introduced. With the deeper of knowledge of pharmacodynamics and pharmacokinetics of the drug system, the design and synthesis of these drugs can be further optimized. Furthermore, the performances of combination with other advanced methodologies and technologies demonstrated that challenges, such as scale production and high expenses, will not hinder the prospective future of lysine-based polymers.

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LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer-encapsulated methotrexate

Al-Natour

Alazzo

Kim

et al. 2019

International Journal of Pharmaceutics: X

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Investigating the intracellular effects of hyperbranched polycation–DNA complexes on lung cancer cells using LC-MS-based metabolite profiling

Abstract: A metabolomics approach is used to assess the molecular mechanisms underlying the effects of polycation gene delivery vectors on lung cancer cells.

Cited by 9 publications

References 67 publications

Metabolic characterisation of THP-1 macrophage polarisation using LC–MS-based metabolite profiling

Metabolic characterisation of THP-1 macrophage polarisation using LC–MS-based metabolite profiling

Recent Advances in Epsilon-Poly-L-Lysine and L-Lysine-Based Dendrimer Synthesis, Modification, and Biomedical Applications

LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer-encapsulated methotrexate

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