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Among non-viral gene delivery vectors, poly(β-amino ester)s (PAEs) are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. Over two decades, PAEs have evolved from linear to highly branched structures, significantly enhancing gene delivery efficacy. Building on the proven efficient sets of monomers in highly branched PAEs (HPAEs), this work introduced a new class of cyclic PAEs (CPAEs) constructed via an A 2  + B 4  + C 2 cyclization synthesis strategy and identified their markedly improved gene transfection capabilities in gene delivery applications. Two sets of cyclic PAEs (CPAEs) with rings of different sizes and topologies were obtained. Their chemical structures were confirmed via two-dimensional nuclear magnetic resonance and the photoluminescence phenomena, and their DNA delivery behaviours were investigated and compared with the HPAE counterparts. In vitro assessments demonstrated that the CPAEs with a macrocyclic architecture (MCPAEs), significantly enhanced DNA intracellular uptake and facilitated efficient gene expression while maintaining perfect biocompatibility. The top-performance MCPAEs have been further employed to deliver a plasmid coding dual single guide RNA-guided CRISPR-Cas9 machinery to delete COL7A1 exon 80 containing the c.6527dupC mutation. In recessive dystrophic epidermolysis bullosa (RDEB) patient-derived epidermal keratinocytes, MCPAEs facilitated the CRISPR plasmid delivery and achieved efficient targeted gene editing in multiple colonies., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gene therapy has emerged as a significant advancement in medicine in recent years. However, the development of effective gene delivery vectors, particularly polymer vectors, remains a significant challenge. Limited understanding of the internal structure of polymer vectors has hindered efforts to enhance their efficiency. This work focuses on investigating the impact of polymer structure on gene delivery, using the well-known polymeric vector poly(β-amino ester) (PAE) as a case study. For the first time, we revealed the distinct characteristics of individual polymer components and their synergistic effects-the appropriate combination of different components within a polymer (high MW and low MW components) on gene delivery. Additionally, artificial intelligence (AI) analysis was employed to decipher the relationship between the polymer component distribution (PCD) and gene transfection performance. Guided by this analysis, a series of highly efficient polymer vectors that outperform current commercial reagents such as jetPEI and Lipo3000 were developed, among which the transfection efficiency of the PAE-B1-based polyplex was approximately 1.5 times that of Lipo3000 and 2 times that of jetPEI in U251 cells.

As a key nonviral gene therapy vector, poly(β-amino ester) (PAE) has demonstrated great potential for clinical application after two decades of development. However, even after extensive efforts in structural optimizations, including screening chemical composition, molecular weight (MW), terminal groups, and topology, their DNA delivery efficiency still lags behind that of viral vectors. To break through this bottleneck, in this work, a thorough investigation of highly branched PAEs (HPAEs) was conducted to correlate their fundamental internal structure with their gene transfection performance. We show that an essential structural factor, branch unit distribution (BUD), plays an important role for HPAE transfection capability and that HPAEs with a more uniform distribution of branch units display better transfection efficacy. By optimizing BUD, a high-efficiency HPAE that surpasses well-known commercial reagents (e.g., Lipofectamine 3000 (Lipo3000), jetPEI, and Xfect) can be generated. This work opens an avenue for the structural control and molecular design of high-performance PAE gene delivery vectors.

Recently, an extensive research effort has been directed toward the improvement of nonviral transfection vectors, such as polymeric materials. The macromolecular structure of polymers has a substantial effect on their transfection efficacy. In this context, the modern advances in polymer production techniques, such as the deactivation-enhanced radical atom transfer polymerization (DE-ATRP), have been fundamental for the synthesis of controlled architecture nanomaterials. In this study, hyperbranched poly(β-pinene)-PDMAEMA-PEGDMA nanometric copolymers were synthesised at high conversion via DE-ATRP using different concentrations of β-pinene for gene delivery applications. The structural characterization and the biological performance of the materials were investigated. The copolymers' molar mass (10,434-16,438 mol l -1 ), dispersity, and conversion (90-95%) varied significantly with β-pinene proportion on the polymerizations. The polymer-gene complexes generated (280-110 nm) presented excellent solution stability due to the β-pinene segment on the copolymers. Gene delivery and transfection were highly dependent on the copolymer composition. The copolymers containing the highest β-pinene proportions exhibited the best results with high transfection effectivity. In conclusion, the incorporation of β-pinene in DMAEMA-PEGMA copolymer formulations is a renewable option to improve the materials' branching ratio, polyplex stability, and gene delivery performance without causing cytotoxic effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Further to conventional linear, branched, crosslinked, and dendritic polymers, single chain cyclized/knotted polymers (SCKPs) have emerged as a new class of polymer structure with unique properties. Herein, the development of bacteria-resistant SCKPs is reported and the effect of this structure on the resistance of polymer materials to bacteria is investigated. Four SCKPs were synthesized by reversible addition fragmentation chain transfer (RAFT) homopolymerization of multivinyl monomers (MVMs) and then crosslinked by UV light to form SCKP films. Regardless of MVM type used, the resulting SCKP films showed much higher resistance to bacteria, and up to 75 % less bacterial attachment and biofilm formation, in comparison with the corresponding non-SCKP films. This is due to the altered surface morphology and hydrophobicity of the SCKP films. These results highlight the critical role of the SCKP structure in enhancing the resistance of polymeric materials to bacteria., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Further to conventional linear, branched, crosslinked, and dendritic polymers, single chain cyclized/knotted polymers (SCKPs) have emerged as a new class of polymer structure with unique properties. Herein, the development of bacteria‐resistant SCKPs is reported and the effect of this structure on the resistance of polymer materials to bacteria is investigated. Four SCKPs were synthesized by reversible addition fragmentation chain transfer (RAFT) homopolymerization of multivinyl monomers (MVMs) and then crosslinked by UV light to form SCKP films. Regardless of MVM type used, the resulting SCKP films showed much higher resistance to bacteria, and up to 75 % less bacterial attachment and biofilm formation, in comparison with the corresponding non‐SCKP films. This is due to the altered surface morphology and hydrophobicity of the SCKP films. These results highlight the critical role of the SCKP structure in enhancing the resistance of polymeric materials to bacteria. [ABSTRACT FROM AUTHOR]

• Active Kinetic Chain Length (AKCL) is a general guideline for well-controlled ATRP. • The smaller AKCL can decrease polydispersity and diminish the radical termination. • The fraction of terminated chains (FTC) depends on the ratio kact[Cu(I)]/kde[Cu(II)] • Comparing the parameter effect in ATRP by equation, MC simulation and experiment. • This AKCL criterion could be extended to other controlled/living polymerizations. Since atom transfer radical polymerization (ATRP) was developed, various strategies have been adopted to design well-controlled ATRP procedures. However, there is no single criterion that could be used for various ATRP reaction conditions (e.g., different monomers, different targeted degrees of polymerization, conversions, etc.). In this work, we introduce a new factor - Active Kinetic Chain Length (AKCL) as a parameter that can guide the design of well-controlled ATRPs. Under a certain reaction system with a specific monomer type (k p), monomer concentration ([M] 0), and targeted degrees of polymerization, the smaller value of AKCL, i.e., a smaller initial number of monomer units added to a growing chain during a chain active period, can decrease polymer dispersity and also diminish the radical termination. The effects of AKCL were compared with other parameters affecting dispersity and livingness in ATRPs, which clearly demonstrates the design principle of AKCL. The model examples of deactivation-enhanced ATRP (DE-ATRP) have further shown the effectiveness of this criterion. [ABSTRACT FROM AUTHOR]

[Display omitted] • A facile and cost-effective route to prepare antibacterial materials was developed. • Preparation process is simply and easily scalable via initiator strategy. • Oxygen-sulfur terminal bonds possessing antibacterial properties were first reported. • Excellent antibacterial activity was exhibited in a wide range of application situations. Bacterial infection has become a long-term concern that seriously threatens human health. However, the application of conventional antibacterial materials in antibacterial treatment and infection prevention has been severely hindered due to their limitations such as complex synthesis, high cost, and high cytotoxicity. Therefore, developing a facile and cost-effective route to prepare high-performance antibacterial materials is of urgent need and significant importance. In this work, we for the first time reported that oxygen-sulfur terminal bonds possess excellent antibacterial properties, and the oxygen-sulfur terminal polymer (OSTP) can effectively kill bacteria when contacting and interacting with the bacteria. A universal and simple initiator strategy has been developed to fabricate OSTPs through a facile solution polymerization process. Via this approach, the PEGDA-APS OSTPs exhibited superfast and superior antibacterial properties against both Gram-positive and Gram-negative bacteria while maintaining good hemocompatibility and cytocompatibility, outperforming many common antibacterial agents that usually require several hours of bacterial extinction. Moreover, it was demonstrated that OSTPs exhibited excellent antibacterial activity in a wide range of application situations, including textile, medicine, washing, food, and coating, as well as antibacterial hydrogels. [ABSTRACT FROM AUTHOR]