Abstract Functionality, one of the key attributes of atom transfer radical polymerization (ATRP), was utilized for the synthesis of well‐controlled polymers functionalized with biotin, pyrene, and peptides. Hydroxy‐functionalized poly(oligo(ethylene oxide) monomethyl ether methacrylate) (HO‐POEOMA) was prepared by AGET ATRP of OEOMA initiated by 2‐hydroxyethyl 2‐bromoisobutyrate in water or in inverse miniemulsion of water/cyclohexane at ambient temperature. HO‐POEOMA was then further functionalized with biotin, pyrene, and GRGDS peptide. In addition, ATRP and click chemistry offered an efficient route for the synthesis of telechelic di‐biotin polymers. These general methods can be applied to the formation of different functional materials conjugated with proteins, dyes, nucleic acids, and drugs. magnified image
Stimuli-responsive degradation (SRD) based on disulfide chemistry is highly desirable in the development of self-assembled block copolymer nanocarriers for multifunctional polymer-based drug delivery systems. In contrast to most conventional approaches involving the incorporation of disulfide linkages at single locations, an effective dual location SRD approach centers on the development of new intracellular nanocarriers having dynamic disulfide linkages in dual or multiple locations. The placement of dynamic disulfide linkages in multiple locations within a nanocarrier exhibit not only synergistically accelerated release due to dual location reduction responses, but also allows additional desirable synergistic therapeutic effects. This chapter describes three strategies to synthesize novel reduction-responsive degradable block copolymers and their self-assembled micelles that have been recently developed utilizing the dual or multi-location stimuli responsive degradation strategy. Their aqueous micellization, reduction-responsive degradation, and intracellular trafficking offer versatility in intracellular anticancer drug delivery applications.
Smart nanoassemblies degradable through the cleavage of acid-labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid-degradable shell-sheddable nanoassemblies. Herein, the authors report the synthesis and acid-responsive degradation through acid-catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid-labile linkage. The authors explore the synthesis and aqueous micellization of well-defined poly(ethylene glycol)-based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally-stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid-catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid-degradable shell-sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid-degradable shell-sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor-targeting drug delivery.
Biosensing technology, which aims to measure and control the signals of biological substances, has recently been developed rapidly due to increasing concerns about health and the environment. Top–down technologies have been used mainly with a focus on reducing the size of biomaterials to the nano-level. However, bottom–up technologies such as self-assembly can provide more opportunities to molecular-level arrangements such as directionality and the shape of biomaterials. In particular, block copolymers (BCPs) and their self-assembly have been significantly explored as an effective means of bottom–up technologies to achieve recent advances in molecular-level fine control and imaging technology. BCPs have been widely used in various biosensing research fields because they can artificially control highly complex nano-scale structures in a directionally controlled manner, and future application research based on interactions with biomolecules according to the development and synthesis of new BCP structures is greatly anticipated. Here, we comprehensively discuss the basic principles of BCPs technology, the current status of their applications in biosensing technology, and their limitations and future prospects. Rather than discussing a specific field in depth, this study comprehensively covers the overall content of BCPs as a biosensing platform, and through this, we hope to increase researchers’ understanding of adjacent research fields and provide research inspiration, thereby bringing about great advances in the relevant research fields.
Der reversible Bruch und die erneute Bildung von Blockcopolymer-Micellen wurden rasterkraftmikroskopisch verfolgt (siehe Bild). Ein eingekapselter hydrophober Farbstoff konnte durch UV-Bestrahlung aus den urspünglichen Micellen freigesetzt werden und lagerte sich überraschend bei der Regenerierung der Micellen durch Bestrahlung mit sichtbarem Licht teilweise wieder ein.
We demonstrate microfluidic manufacturing of glutathione (GSH)-responsive polymer nanoparticles (PNPs) with controlled in vitro pharmacological properties for selective drug delivery. This work leverages previous fundamental work on microfluidic control of the physicochemical properties of GSH-responsive PNPs containing cleavable disulfide groups in two different locations (core and interface, DualM PNPs). In this paper, we employ a two-phase gas-liquid microfluidic reactor for the flow-directed manufacturing of paclitaxel-loaded or DiI-loaded DualM PNPs (PAX-PNPs or DiI-PNPs, where DiI is a fluorescent drug surrogate dye). We find that both PAX-PNPs and DiI-PNPs exhibit similar flow-tunable sizes, morphologies, and internal structures to those previously described for empty DualM PNPs. Fluorescent imaging of DiI-PNP formulations shows that microfluidic manufacturing greatly improves the homogeneity of drug dispersion within the PNP population compared to standard bulk microprecipitation. Encapsulation of PAX in DualM PNPs significantly increases its selectivity to cancerous cells, with various PAX-PNP formulations showing higher cytotoxicity against cancerous MCF-7 cells than against non-cancerous HaCaT cells, in contrast to free PAX, which showed similar cytotoxicity in the two cell lines. In addition, the characterization of DualM PNP formulations formed at various microfluidic flow rates reveals that critical figures of merit for drug delivery function-including encapsulation efficiencies, GSH-triggered release rates, rates of cell uptake, cytotoxicities, and selectivity to cancerous cells-exhibit microfluidic flow tunability that mirrors trends in PNP size. These results highlight the potential of two-phase microfluidic manufacturing for controlling both structure and drug delivery function of biological stimuli-responsive nanomedicines toward improved therapeutic outcomes.
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