Bottlebrush polyethylene glycol nanocarriers translocate across human airway epithelium via molecular architecture enhanced endocytosis DOI Open Access

Zhi-Jian He,

Baiqiang Huang, Li‐Heng Cai

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 16, 2024

Pulmonary drug delivery is critical to the treatment of respiratory diseases. However, human airway surface presents multiscale barriers efficient delivery. Here we report a bottlebrush polyethylene glycol (PEG-BB) nanocarrier that can translocate across all within surface. Guided by molecular theory, design PEG-BB molecule consisting linear backbone densely grafted many (∼1,000) low weight (∼1000 g/mol) PEG chains; this results in highly anisotropic, wormlike featuring contour length ∼250 nm, cross-section ∼20 and hydrodynamic diameter ∼40 nm. Using classic air-liquid-interface culture system recapitulate essential biological features surface, show rapidly penetrates through endogenous mucus periciliary brush layer (mesh size 20-40 nm) be internalized cells whole epithelium. By quantifying cellular uptake polymeric carriers various architectures manipulating cell proliferation endocytosis pathways, translocation epithelium driven architecture enhanced endocytosis. Our demonstrate large, polymers, if properly designed, used as novel carrier for pulmonary mucosal

Язык: Английский

Polymers as Efficient Non-Viral Gene Delivery Vectors: The Role of the Chemical and Physical Architecture of Macromolecules DOI Open Access
Majad Khan

Polymers, Год журнала: 2024, Номер 16(18), С. 2629 - 2629

Опубликована: Сен. 18, 2024

Gene therapy is the technique of inserting foreign genetic elements into host cells to achieve a therapeutic effect. Although gene was initially formulated as potential remedy for specific problems, it currently offers solutions many diseases with varying inheritance patterns and acquired diseases. There are two major groups vectors therapy: viral vector non-viral therapy. This review examines role macromolecule's chemical physical architecture in delivery, including their design synthesis. Polymers can boost circulation, improve control cargo release through various methods. The prominent examples discussed include poly-L-lysine, polyethyleneimine, comb polymers, brush star well hydrogels natural polymers modifications. While significant progress has been made, challenges still exist stabilization, targeting specificity, cellular uptake. Overcoming cytotoxicity, improving delivery efficiency, utilizing hybrid systems vital factors prospects. comprehensive provides an illuminating overview field, guiding way toward innovative non-viral-based solutions.

Язык: Английский

Процитировано

11

Recent progress of non-linear topological structure polymers: synthesis, and gene delivery DOI Creative Commons
Chenfei Wang, Wei He,

Feifei Wang

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 27, 2024

Abstract Currently, many types of non-linear topological structure polymers, such as brush-shaped, star, branched and dendritic structures, have captured much attention in the field gene delivery nanomedicine. Compared with linear structural polymers offer advantages, including multiple terminal groups, broad complicated spatial architecture multi-functionality sites to enhance efficiency targeting capabilities. Nevertheless, complexity their synthesis process severely hampers development applications nonlinear polymers. This review aims highlight various synthetic approaches reversible-deactivation radical polymerization (RDRP) atom-transfer (ATRP), nitroxide-mediated (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, click chemistry reactions Michael addition, thoroughly discuss advantages disadvantages, well analyze further application potential. Finally, we comprehensively summarize different for genetic materials delivering performance both vitro vivo, which indicated that effects topologies play a crucial role enhancing transfection polymeric vectors. offered promising guideline design novel facilitated new generation polymer-based

Язык: Английский

Процитировано

8

Hydrophilic Poly(meth)acrylates by Controlled Radical Branching Polymerization: Hyperbranching and Fragmentation DOI Creative Commons
Kriti Kapil, Arman Moini Jazani, Julian Sobieski

и другие.

Macromolecules, Год журнала: 2024, Номер 57(11), С. 5368 - 5379

Опубликована: Май 29, 2024

Topology significantly impacts polymer properties and applications. Hyperbranched polymers (HBPs) synthesized via atom transfer radical polymerization (ATRP) using inimers typically exhibit broad molecular weight distributions limited control over branching. Alternatively, copolymerization of inibramers (IB), such as α-chloro/bromo acrylates with vinyl monomers, yields HBPs precise uniform Herein, we described the synthesis hydrophilic HB polyacrylates in water by copolymerizing a water-soluble IB, oligo(ethylene oxide) methyl ether 2-bromoacrylate (OEOBA), various acrylate comonomers. Visible-light-mediated controlled branching (CRBP) dual catalysis eosin Y (EY) copper complexes resulted weights (Mn = 38 000 to 170 000) degrees (2%–24%). Furthermore, optimized conditions enabled successful application OEOBA synthesize linear-hyperbranched block copolymers hyperbranched protein hybrids (HB-PPH), demonstrating its potential advance complex macromolecular architecture under environmentally benign conditions. Copolymerization methacrylate monomer, (OEOMA500), inibramer was accompanied fragmentation β-carbon C–C bond scission subsequent growth chains from fragments. computational studies investigating depending on IB comonomer structure supported experimental observations. This work expands toolkit for CRBP highlights critical influence reaction outcomes.

Язык: Английский

Процитировано

7

Nitroxide radical contrast agents for safe magnetic resonance imaging: progress, challenges, and perspectives DOI
Xiaobing Yuan, Haojie Yu, Li Wang

и другие.

Materials Horizons, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Magnetic resonance imaging (MRI) is considered one of the most valuable diagnostic technologies in 21st century. To enhance image contrast anatomical features, MRI agents have been widely used clinical diagnosis, especially those based on gadolinium, manganese, and iron oxide. However, these metal-based show potential toxicity to patients, which urges researchers develop novel that can replace agents. Metal-free nitroxide radical (NRCAs) effectively overcome shortcomings also many advantages, including good biocompatibility, prolonged systemic circulation time, easily functionalized structures. Importantly, since NRCAs acquire signals with standard tissue water

Язык: Английский

Процитировано

1

3D Printable Modular Soft Elastomers from Physically Cross-linked Homogeneous Associative Polymers DOI Creative Commons
Myoeum Kim, Shifeng Nian, Daniel A. Rau

и другие.

ACS Polymers Au, Год журнала: 2024, Номер 4(2), С. 98 - 108

Опубликована: Янв. 4, 2024

Three-dimensional (3D) printing of elastomers enables the fabrication many technologically important structures and devices. However, there remains a critical need for development reprocessable, solvent-free, soft that can be printed without post-treatment. Herein, we report modular suitable direct ink writing (DIW) by physically cross-linking associative polymers with high fraction reversible bonds. We designed synthesized linear-associative-linear (LAL) triblock copolymers; middle block is an polymer carrying amide groups form double hydrogen bonding, end blocks aggregate to hard glassy domains effectively act as physical cross-links. The do not nanoscale clusters only slow down dynamics changing shape linear viscoelastic spectra; this molecular control over energy dissipation varying groups. Increasing volume increases network stiffness more than 100 times significantly compromising extensibility. created Young's moduli ranging from 8 kPa MPa while maintaining tensile breaking strain around 150%. Using high-temperature DIW platform, transformed our complex, highly deformable 3D involving any solvent or post-print processing. Our represent softest melt reprocessable materials printing. developed LAL synergize emerging homogeneous bonds classical copolymer self-assembly dual-cross-linked network, providing versatile platform design elastomeric practical applications.

Язык: Английский

Процитировано

5

Dynamics of Associative Polymers with High Density of Reversible Bonds DOI
Shifeng Nian, Shalin Patil, Siteng Zhang

и другие.

Physical Review Letters, Год журнала: 2023, Номер 130(22)

Опубликована: Май 31, 2023

An associative polymer carries many stickers that can form reversible associations. For more than 30 years, the understanding has been associations change shape of linear viscoelastic spectra by adding a rubbery plateau in intermediate frequency range, at which have not yet relaxed and thus effectively act as crosslinks. Here, we design synthesize new classes unentangled polymers carrying unprecedentedly high fractions stickers, up to eight per Kuhn segment, strong pairwise hydrogen bonding ∼20kBT without microphase separation. We experimentally show bonds significantly slow down dynamics but nearly do spectra. This behavior be explained renormalized Rouse model highlights an unexpected influence on structural relaxation polymers.Received 3 May 2022Revised 2 February 2023Accepted 19 April 2023DOI:https://doi.org/10.1103/PhysRevLett.130.228101© 2023 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasHydrogen bondsRheologyPhysical SystemsPolymer meltsPolymer networksTechniquesPolymer theoryRouse modelPolymers & Soft Matter

Язык: Английский

Процитировано

11

A universal strategy for decoupling stiffness and extensibility of polymer networks DOI Creative Commons
Baiqiang Huang, Shifeng Nian, Li‐Heng Cai

и другие.

Science Advances, Год журнала: 2024, Номер 10(48)

Опубликована: Ноя. 27, 2024

Since the invention of polymer networks such as cross-linked natural rubber in 19th century, it has been a dogma that stiffer are less stretchable. We report universal strategy for decoupling stiffness and extensibility single-network elastomers. Instead using linear polymers network strands, we use foldable bottlebrush polymers, which feature collapsed backbone grafted with many side chains. Upon elongation, unfolds to release stored length, enabling remarkable extensibility. By contrast, elastic modulus is inversely proportional strand mass determined by validate this concept creating elastomers nearly constant Young’s (30 kilopascals) while increasing tensile breaking strain 40-fold, from 20 800%. show applies different species topologies. Our discovery opens an avenue developing polymeric materials extraordinary mechanical properties.

Язык: Английский

Процитировано

4

UV Irradiation-Induced Cyclic-to-Linear Topological Changes of a Light/pH Dual-Sensitive Cyclic Copolymer for Enhanced Drug Delivery DOI
Hongbing Liu,

Zheng Guo,

Wei Ma

и другие.

ACS Macro Letters, Год журнала: 2023, Номер 12(8), С. 1025 - 1030

Опубликована: Июль 11, 2023

Cyclic polymers with cleavable backbones triggered by either external or internal stimuli can realize simultaneous extracellular stability and intracellular destabilization of cyclic polymer-based nanocarriers but remain seldom reported. To this end, we prepared herein cyclic-ONB-P(OEGMA-st-DMAEMA) (c-ONB-P(OEGMA-st-DMAEMA)) a light-cleavable junction in the polymer backbone based on oligo (ethylene glycol) monomethyl ether methacrylate (OEGMA) N,N-dimethylaminoethyl (DMAEMA) using atom transfer radical polymerization (ATRP) initiator containing an o-nitrobenzyl (ONB) ester group. Together pH-sensitivity DMAEMA, c-ONB-P(OEGMA-st-DMAEMA) shows mainchain pH-sensitive side chains. Notably, doxorubicin (DOX)-loaded c-ONB-P(OEGMA4-st-DMAEMA38) (C2) micelles mediated IC50 value 2.28 μg/mL Bel-7402 cells, which is 1.7-fold lower than that acquired without UV irradiation. This study thus reported synthesis copolymer UV-cleavable uncovered effects topological modulation vitro controlled release properties polymers.

Язык: Английский

Процитировано

9

Bottlebrush Polyethylene Glycol Nanocarriers Translocate across Human Airway Epithelium via Molecular Architecture-Enhanced Endocytosis DOI Creative Commons

Zhi-Jian He,

Baiqiang Huang, Li‐Heng Cai

и другие.

ACS Nano, Год журнала: 2024, Номер 18(27), С. 17586 - 17599

Опубликована: Июнь 27, 2024

Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, human airway surface presents multiple barriers to efficient delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all within surface. Guided by molecular theory, design PEG-BB molecule consisting linear backbone densely grafted many (∼1000) low weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in highly anisotropic, wormlike featuring contour length ∼250 nm, cross-section ∼20 and hydrodynamic diameter ∼40 nm. Using classic air-liquid-interface culture system recapitulate essential biological features surface, show rapidly penetrates through endogenous mucus periciliary brush layer (mesh size 20-40 nm) be internalized cells whole epithelium. By quantifying cellular uptake polymeric carriers various architectures manipulating cell proliferation endocytosis pathways, translocation epithelium driven architecture-enhanced endocytosis. Our demonstrate large, PEG polymers, if properly designed, used as carrier pulmonary mucosal

Язык: Английский

Процитировано

3

Crystallization of Bottlebrush Statistical Copolymers of Polystyrene and Poly(ethylene oxide) DOI
X. Gan, Hong‐Gyu Seong, Mingqiu Hu

и другие.

Macromolecules, Год журнала: 2024, Номер 57(15), С. 7306 - 7314

Опубликована: Июль 16, 2024

Язык: Английский

Процитировано

3