المؤلفون: Liu, Luofu¹ (AUTHOR), Duan, Chao¹ (AUTHOR), Wang, Rui^1,2 (AUTHOR) ruiwang325@berkeley.edu

المصدر: Journal of Chemical Physics. 1/14/2024, Vol. 160 Issue 2, p1-8. 8p.

مصطلحات موضوعية: *SELF-consistent field theory, *POLYMERSOMES, *SINGLE parents, *MICROMECHANICS, *PHYSICAL & theoretical chemistry, *ENERGY function

مستخلص: Despite the wide existence of vesicles in living cells as well as their important applications like drug delivery, the underlying mechanism of vesicle fusion/fission remains under debate. Classical models cannot fully explain recent observations in experiments and simulations. Here, we develop a constrained self-consistent field theory that allows tracking the shape evolution and free energy as a function of center-of-mass separation distance. Fusion and fission are described in a unified framework. Both the kinetic pathway and the mechanical response can be simultaneously captured. By taking vesicles formed by polyelectrolytes as a model system, we predict discontinuous transitions between the three morphologies: parent vesicle with a single cavity, hemifission/hemifusion, and two separated child vesicles, as a result of breaking topological isomorphism. With the increase in inter-vesicle repulsion, we observe a great reduction in the cleavage energy, indicating that vesicle fission can be achieved without hemifission, in good agreement with simulation results. The force–extension relationship elucidates typical plasticity for separating two vesicles. The super extensibility in the mechanical response of vesicle is in stark contrast to soft particles with other morphologies, such as cylinder and sphere. Our work elucidates the fundamental physical chemistry based on intrinsic topological features of vesicle fusion/fission, which provides insights into various phenomena observed in experiments and simulations. [ABSTRACT FROM AUTHOR]

المؤلفون: Pan, Hui¹ (AUTHOR), Zhang, Changxu¹ (AUTHOR), Jiang, Wenfeng¹ (AUTHOR) jiangwenfeng@sjtu.edu.cn, Zhou, Yongfeng¹ (AUTHOR) yfzhou@sjtu.edu.cn

المصدر: Angewandte Chemie International Edition. Jul2024, Vol. 63 Issue 27, p1-6. 6p.

مصطلحات موضوعية: *UNIFORM polymers, *POLYMERSOMES, *POLYMERS, *PHYSICS

مستخلص: Artificial vesicles are recognized as powerful platforms for a large body of research across the disciplines of chemistry, physics and biology. Despite the great progress, control of the size distribution to make uniform vesicles remains fundamentally difficult due to the highly uncontrollable growth kinetics, especially for micron‐sized vesicles. Here we report a template‐free living self‐assembly method to prepare monodisperse vesicles around 1 μm from an alternating copolymer. The polymer forms nanodisks (ca. 9 nm) in N,N‐dimethylformamide (DMF), acting as seeds for subsequent growth. By adding water, the nanodisks gradually grow into larger circular bilayer nanosheets, which bend to crowns and continue to grow into uniform micron‐sized vesicles. The first‐order growth kinetics as well as the small size polydispersity index (<0.1) suggests the living self‐assembly characteristics. This work paves a new way in both living self‐assembly and monodisperse polymer vesicles. [ABSTRACT FROM AUTHOR]

المؤلفون: Rutjes, Floris P. J. T.¹ (AUTHOR) floris.rutjes@ru.nl, Bonger, Kimberly M.¹ (AUTHOR) k.bonger@science.ru.nl, Neumann, Kevin¹ (AUTHOR) kevin.neumann@ru.nl

المصدر: Synlett. Jul2024, Vol. 35 Issue 11, p1230-1238. 9p.

مصطلحات موضوعية: *POLYMERSOMES, *DIELS-Alder reaction, *ORGANIC synthesis, *AMINO acid derivatives, *MATERIALS science

مستخلص: This article provides an overview of the field of bioorthogonal chemistry and its advancements at Radboud University. Bioorthogonal chemistry involves conducting chemical reactions within a biological environment with high selectivity and compatibility. Radboud University has made significant contributions to this field, including the development of strained alkynes and the synthesis of bioorthogonal tools such as BCN and TCO. These tools have been applied in various areas such as chemical biology and materials science. The article also highlights the interdisciplinary nature of research at Radboud University and the importance of synthetic availability in bioorthogonal reagents. The text specifically discusses the use of VBAs in bioorthogonal chemistry, particularly in the IEDDA reaction with tetrazines. The authors found that introducing boronic acid substituents on linear alkenes improved their reactivity in the IEDDA reaction. They also observed that the reactivity of VBAs varied depending on the coordinating substituent on the tetrazine. The authors explored the potential of VBAs in click-to-release chemistry, protein modification, and drug delivery applications. The article emphasizes the collaborative efforts and interdisciplinary approach necessary for advancing bioorthogonal chemistry. [Extracted from the article]

المؤلفون: Kung, Yi¹ (AUTHOR), Chien, Wei-Chun² (AUTHOR), Huang, Hsin-Yu² (AUTHOR), Shen, Hsin-Hsin³ (AUTHOR), Chen, Sen-Lu³ (AUTHOR), Yu, Wei-Lin³ (AUTHOR), Wang, Yu-Chi³ (AUTHOR), Chen, Wen-Shiang^2,4 (AUTHOR), Wu, Chueh-Hung^2,5 (AUTHOR) nojred@gmail.com

المصدر: International Journal of Polymeric Materials & Polymeric Biomaterials. 2024, Vol. 73 Issue 10, p866-874. 9p.

مصطلحات موضوعية: *GROWTH factors, *POLYMERSOMES, *PLATELET-rich plasma, *HYALURONIC acid, *THERMORESPONSIVE polymers, *ETHYLENE glycol

مستخلص: Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection is commonly used for the treatment of osteoarthritis. However, the immediate bolus release of growth factors from PRP and inability of HA to stay in situ limit their beneficial therapeutic effects. An injectable, biocompatible, and thermoresponsive hydrogel (mPEG-PLGA-BOX block copolymer) is applicable for a long-term ultrasound-triggered lyophilized platelet (LP) release. In this study, an US-controlled release thermoresponsive hydrogel system loaded with LPs was evaluated for its long-term pharmacokinetics in a dry culture chamber at 37 °C. At 0.5 wt% constituent ratio of the LP-loaded hydrogels (0.2 ± 0.6 mV positively charged, which would be suitable for the treatments of negatively charged cartilages), the release amount of growth factors (PDGF-B and TGFβ-1) from the hydrogel could be increased to ∼300-folds in the presence of US (1 MHz, 0.4 W/cm2, 5% duty cycle, 5 min) compared to the amount in the absence of US during the 2 weeks of evaluation period. In comparison to 0.5 wt% of the LP-loaded HA (−2.4 ± 1.1 mV negatively charged), which had only a 5-day release ability, the US-controlled release thermoresponsive hydrogel system may be a more suitable platform for diseases that needed long-term treatments. [ABSTRACT FROM AUTHOR]

المؤلفون: Tian, Xiao¹, Zhang, Yunpeng¹, Zhang, Meng¹, Liu, Gang¹, Hao, Yuedong¹, Liu, Weidong¹ lwdhayy@126.com

المصدر: Nanotoxicology. Jun2024, p1-9. 9p. 6 Illustrations.

مصطلحات موضوعية: *POLYMERSOMES, *DOXORUBICIN, *DRUG resistance, *OSTEOSARCOMA, *TREATMENT effectiveness, *ANDERSON localization, *POLYCAPROLACTONE, *GLUTATHIONE peroxidase

مستخلص: AbstractTo determine the effects of polymeric nanoparticle for doxorubicin (Dox) delivery and treatment of drug-resistant Osteosarcoma (OS) cells. Methoxy-polyethylene glycol amino (mPEG-NH2) and platinum bio-mimetic polycaprolactone-cysteine (PtBMLC) were crosslinked to obtain glutathione (GSH)-responsive mPEG-NH2-PtBMLC polymer to encapsulate Dox (named as Nano-Dox). The particle size and zeta potential of the nanoparticles were measured, and internalization of Dox by OS cells was observed. After treatment with Nano-Dox, cell proliferation was determined by cell counting kit 8 (CCK-8) and colony formation assay. Cell migration and invasion were determined by Transwell assay. Cell cycle arrest was assessed by flow cytometry. The induction of ferroptosis was analyzed by abnormal accumulation of total iron, Fe2+. Nano-Dox exhibited a stronger localization in OS cells (p < 0.01). Nano-Dox induced more significant suppression of drug-resistant OS cell growth (p < 0.01), migration (p < 0.01), and invasion (p < 0.01), compared with the single Dox treatment group, along with decreased expression of N-cadherin, Snail, and Vimentin, suggesting impaired cancer migration and invasion. The treatment with Nano-Dox induced notable cell cycle arrest at G0/G1 phase (p < 0.01) and accumulation of iron, Fe2+, and MDA (p < 0.01), as well as suppressed the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11. Administration of ferroptosis inhibitor (Fer-1) reversed the anti-proliferation effects of Nano-Dox (p < 0.01). The Dox delivered by the polymeric nanoparticle system notably enhanced its effects on suppressing the growth, migration, and invasion of drug-resistant OS cells via inducing ferroptosis. The application of environment response polymer enhanced the delivery of Dox and the therapeutic effects on OS. [ABSTRACT FROM AUTHOR]

المؤلفون: Jain, Monika¹ (AUTHOR), Ukani, Hiral¹ (AUTHOR), Kumar, Sugam² (AUTHOR), Aswal, Vinod K.² (AUTHOR), Kailasa, Suresh Kumar¹ (AUTHOR), El Seoud, Omar A.³ (AUTHOR), Malek, Naved I.^1,3 (AUTHOR) navedmalek@chem.svnit.ac.in

المصدر: ChemistrySelect. Jun2024, Vol. 9 Issue 22, p1-10. 10p.

مصطلحات موضوعية: *CURCUMIN, *POLYMERSOMES, *SURFACE potential, *IONIC liquids, *TREATMENT effectiveness, *DRUG efficacy, *DRUG carriers

مستخلص: Nano vehicles for drug delivery with stimuli‐responsive characteristics are gaining prominence due to their ability to enhance traditional drug delivery methods by minimizing side effects and improving drug efficacy. Among the various stimuli‐responsive systems, pH‐responsive drug delivery nano vehicles have garnered significant attention. Utilizing this pH variance, tailored drug delivery nano vehicles can release encapsulated drugs on demand. Here, we developed pH‐responsive catanionic vesicles to create customized drug delivery nano vehicles responsive to stimuli, particularly pH. we have designed catanionic vesicles through interacting two oppositely charged surface active ionic liquids (SAILs), i. e. cationic ‐methyl‐4‐(2‐(dodecyloxycarbonylmethyl)morpholin‐4‐ium bromide [C12EMorph][Br] with anionic Choline Oleate ([Ch][Ol]). The spherically shaped micellar aggregates of [C12EMorph][Br] are transformed into pH responsive vesicular nanoaggregates through judicious addition of [Ch][Ol]. The morphological transition was studied through various analytical techniques including DLS, FRET and SANS. We used these pH responsive vesicular nanoaggregates to load representative hydrophobic drug curcumin in order to enhance its solubility, efficacy and bioavailability. This innovative approach in designing pH‐responsive vesicular nanoaggregates using two biocompatible SAILs signifies a breakthrough in biomedical research, holding promise for advancements in drug delivery and therapeutic applications. [ABSTRACT FROM AUTHOR]

المؤلفون: Lu, Zhouxia^1,2 (AUTHOR) lzx5882@sina.com, Chen, Xu¹ (AUTHOR) pandaxxu@outlook.com, Wang, Conghui¹ (AUTHOR) wch1515689971@sina.com, Luo, Xuelian¹ (AUTHOR) 15121604241lxl@sina.com, Wu, Xiaohan¹ (AUTHOR) qq2824836751@sina.com, Zhao, Xing³ (AUTHOR) xingzhao@gmc.edu.cn, Xiao, Song^1,3 (AUTHOR) xiaosong@gmc.edu.cn

المصدر: Pharmaceutics. Jun2024, Vol. 16 Issue 6, p822. 17p.

مصطلحات موضوعية: *PHOTODYNAMIC therapy, *POLYMERSOMES, *NEUROBLASTOMA, *REACTIVE oxygen species, *NANOCOMPOSITE materials, *TUMOR growth

مستخلص: DOX/TPOR4@CB[7]4 was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of photodynamic therapy on SH-SY5Y cells was assessed using the MTT assay, while flow cytometry analysis was employed to detect cell apoptosis. Confocal laser scanning microscopy was utilized to observe the intracellular distribution of DOX/TPOR4@CB[7]4 in SH-SY5Y cells. Additionally, fluorescence imaging of DOX/TPOR4@CB[7]4 in nude mice bearing SH-SY5Y tumors and examination of the combined effects of photodynamic and chemical therapies were conducted. The incorporation of CB[7] significantly enhanced the optical properties of DOX/TPOR4@CB[7]4, resulting in increased ROS production and pronounced toxicity towards SH-SY5Y cells. Moreover, both the apoptotic and mortality rates exhibited significant elevation. In vivo experiments demonstrated that tumor growth inhibition was most prominent in the DOX/TPOR4@CB[7]4 group. π–π interactions facilitated the binding between DOX and photosensitizer TPOR, with TPOR's naphthalene hydrophilic groups encapsulated within CB[7]'s cavity through host–guest interactions with CB[7]. Therefore, CB[7] can serve as a nanocarrier to enhance the combined application of chemical therapy and photodynamic therapy, thereby significantly improving treatment efficacy against neuroblastoma tumors. [ABSTRACT FROM AUTHOR]

المؤلفون: Saraiva, Nuno M.^1,2 (AUTHOR) nunommsaraiva@gmail.com, Alves, Ana^3,4 (AUTHOR) anadaniela92@hotmail.com, Costa, Paulo C.^3,4 (AUTHOR) pccosta@ff.up.pt, Correia-da-Silva, Marta^1,2 (AUTHOR) m_correiadasilva@ff.up.pt

المصدر: Pharmaceuticals (14248247). Jun2024, Vol. 17 Issue 6, p747. 16p.

مصطلحات موضوعية: *POLYMERSOMES, *CLICK chemistry, *CHEMICAL reactions, *COORDINATION polymers, *BLOCK copolymers, *FUNCTIONAL groups, *LIGANDS (Chemistry)

مستخلص: Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide–alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies. [ABSTRACT FROM AUTHOR]

المؤلفون: Wardhani, Kartika^1,2 (AUTHOR) kwardhani@lanl.gov, Levina, Aviva¹ (AUTHOR) haipei.zou@outlook.com, Sun, Biyun³ (AUTHOR) biyun.sun@mq.edu.au, Zou, Haipei¹ (AUTHOR), Grau, Georges E. R.^4,5,6,7 (AUTHOR) georges.grau@sydney.edu.au, Keene, F. Richard^8,9 (AUTHOR), Collins, J. Grant¹⁰ (AUTHOR) grant.collins@unsw.edu.au, Lay, Peter A.^1,4,5,6,11 (AUTHOR) peter.lay@sydney.edu.au

المصدر: Biomolecules (2218-273X). Jun2024, Vol. 14 Issue 6, p664. 14p.

مصطلحات موضوعية: *EXTRACELLULAR vesicles, *POLYMERSOMES, *LUNGS, *STAINS & staining (Microscopy), *BACTERIAL diseases

مستخلص: Selective staining of extracellular vesicles (EVs) is a major challenge for diagnostic and therapeutic applications. Herein, the EV labeling properties of a new class of tetranuclear polypyridylruthenium(II) complexes, Rubb7-TNL and Rubb7-TL, as phosphorescent stains are described. These new stains have many advantages over standard stains to detect and characterize EVs, including: high specificity for EV staining versus cell staining; high phosphorescence yields; photostability; and a lack of leaching from EVs until incorporation with target cells. As an example of their utility, large EVs released from control (basal) or lipopolysaccharide (LPS)-stimulated THP-1 monocytic leukemia cells were studied as a model of immune system EVs released during bacterial infection. Key findings from EV staining combined with flow cytometry were as follows: (i) LPS-stimulated THP-1 cells generated significantly larger and more numerous large EVs, as compared with those from unstimulated cells; (ii) EVs retained native EV physical properties after staining; and (iii) the new stains selectively differentiated intact large EVs from artificial liposomes, which are models of cell membrane fragments or other lipid-containing debris, as well as distinguished two distinct subpopulations of monocytic EVs within the same experiment, as a result of biochemical differences between unstimulated and LPS-stimulated monocytes. Comparatively, the staining patterns of A549 epithelial lung carcinoma-derived EVs closely resembled those of THP-1 cell line-derived EVs, which highlighted similarities in their selective staining despite their distinct cellular origins. This is consistent with the hypothesis that these new phosphorescent stains target RNA within the EVs. [ABSTRACT FROM AUTHOR]

المؤلفون: Guerricchio, Laura¹ (AUTHOR) laura.guerricchio@edu.unige.it, Barile, Lucio^2,3 (AUTHOR) lucio.barile@eoc.ch, Bollini, Sveva^1,4 (AUTHOR) sveva.bollini@unige.it

المصدر: International Journal of Molecular Sciences. Jun2024, Vol. 25 Issue 11, p6187. 21p.

مصطلحات موضوعية: *EXTRACELLULAR vesicles, *POLYMERSOMES, *REGENERATIVE medicine, *MYOCARDIAL infarction, *HEART diseases, *HEART failure, *HEART transplantation

مستخلص: Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure. The functional profiling of the biological activity of extracellular vesicles (EVs) has recently attracted increasing interest in the field of translational research for cardiac regenerative medicine. The cardioprotective and cardioactive potential of human progenitor stem/cell-derived EVs has been reported in several preclinical studies, and EVs have been suggested as promising paracrine therapy candidates for future clinical translation. Nevertheless, some compelling aspects must be properly addressed, including optimizing delivery strategies to meet patient needs and enhancing targeting specificity to the cardiac tissue. Therefore, in this review, we will discuss the most relevant aspects of the therapeutic potential of EVs released by human progenitors for cardiovascular disease, with a specific focus on the strategies that have been recently implemented to improve myocardial targeting and administration routes. [ABSTRACT FROM AUTHOR]