Controlled Membrane Transport in Polymeric Biomimetic Nanoreactors.

Polymersome-based biomimetic nanoreactors (PBNs) have generated great interest in nanomedicine and cell mimicry due to their robustness, tuneable chemistry, and broad applicability in biologically relevant fields. In this concept review, we mainly discuss the state of the art in functional polymersomes as biomimetic nanoreactors with membrane-controlled transport. PBNs that use environmental changes or external stimuli to adjust membrane permeability while maintaining structural integrity are highlighted. By encapsulating catalytic species, PBNs are able to convert inactive substrates into functional products in a controlled manner. In addition, special attention is paid to the use of PBNs as tailored artificial organelles with biomedical applications in vitro and in vivo, facilitating the fabrication of next-generation artificial organelles as therapeutic nanocompartments.

Confining the Sol-Gel Reaction at the Water/Oil Interface: Creating Compartmentalized Enzymatic Nano-Organelles for Artificial Cells.

Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous-core silica nanocapsules. In order to confine the sol-gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi-permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme-carrying nanocapsules, as synthetic nano-organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.

Synthetic Cells: From Simple Bio-Inspired Modules to Sophisticated Integrated Systems.

Bottom-up synthetic biology is the science of building systems that mimic the structure and function of living cells from scratch. To do this, researchers combine tools from chemistry, materials science, and biochemistry to develop functional and structural building blocks to construct synthetic cell-like systems. The many strategies and materials that have been developed in recent decades have enabled scientists to engineer synthetic cells and organelles that mimic the essential functions and behaviors of natural cells. Examples include synthetic cells that can synthesize their own ATP using light, maintain metabolic reactions through enzymatic networks, perform gene replication, and even grow and divide. In this Review, we discuss recent developments in the design and construction of synthetic cells and organelles using the bottom-up approach. Our goal is to present representative synthetic cells of increasing complexity as well as strategies for solving distinct challenges in bottom-up synthetic biology.

Synthetic Silica Nano-Organelles for Regulation of Cascade Reactions in Multi-Compartmentalized Systems.

In eukaryotic cells, enzymes are compartmentalized into specific organelles so that different reactions and processes can be performed efficiently and with a high degree of control. In this work, we show that these features can be artificially emulated in robust synthetic organelles constructed using an enzyme co-compartmentalization strategy. We describe an in situ encapsulation approach that allows enzymes to be loaded into silica nanoreactors in well-defined compositions. The nanoreactors can be combined into integrated systems to produce a desired reaction outcome. We used the selective enzyme co-compartmentalization and nanoreactor integration to regulate competitive cascade reactions and to modulate the kinetics of sequential reactions involving multiple nanoreactors. Furthermore, we show that the nanoreactors can be efficiently loaded into giant polymer vesicles, resulting in multi-compartmentalized microreactors.

Membrane Manipulation of Giant Unilamellar Polymer Vesicles with a Temperature-Responsive Polymer.

Understanding the complex behavior and dynamics of cellular membranes is integral to gain insight into cellular division and fusion processes. Bottom-up synthetic cells are as a platform for replicating and probing cellular behavior. Giant polymer vesicles are more robust than liposomal counterparts, as well as having a broad range of chemical functionalities. However, the stability of the membrane can prohibit dynamic processes such as membrane phase separation and division. Here, we present a method for manipulating the membrane of giant polymersomes using a temperature responsive polymer. Upon elevation of temperature deformation and phase separation of the membrane was observed. Upon cooling, the membrane relaxed and became homogeneous again, with infrequent division of the synthetic cells.

Is high-intensity focused ultrasound (HIFU) an option for neoadjuvant therapy for borderline resectable pancreatic cancer patients? - a systematic review.

INTRODUCTION: Pancreatic cancer is with the poorest prognosis of all common cancers worldwide. Despite the advances in treatment the results are poor throughout the different methods. Pancreatic resection still yields the best outcome. However only a quarter of the patients present at operable stage. HIFU is a noninvasive technique that can be used to treat pancreatic cancer. AIM: The aim of this review is to perform a systematic review on the data about the resection rate after HIFU ablation in patients with borderline resectable pancreatic cancer (BRPC) and the impact of this technique over the oncological results. MATERIALS AND METHODS: The PubMed and Wanfang databases were searched using keywords: pancreatic cancer, HIFU ablation and high-intensity focused ultrasound. All found articles were reviewed. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard guidelines. This study was financially supported by 2019 'Kuan-Ren Elite' Program of 2nd Affiliated Hospital of Chongqing Medical University, China (Grant no. KY2019G019). RESULTS: The English database search showed 109 papers, of which 3 met the inclusion criteria. The Wanfang database resulted in 110 papers; however, none met the inclusion criteria of the review. From the included studies 97 patients underwent neoadjuvant HIFU ablation ± chemotherapy. Thirty-four patients reached resection (35.1%). In two patients, residual tumor (R) classification was not reported. R0 resection rate in all reported patients is 30.5% (29/95). R1 resection rate is 3.2% (3/95). CONCLUSION: HIFU is found to be safe and feasible in locally advanced and metastatic pancreatic cancer with proven downstaging and downsizing effects. Further research on role of HIFU ablation as a neoadjuvant treatment for borderline resectable pancreatic cancer is needed.

Dipeptide coacervates as artificial membraneless organelles for bioorthogonal catalysis.

Artificial organelles can manipulate cellular functions and introduce non-biological processes into cells. Coacervate droplets have emerged as a close analog of membraneless cellular organelles. Their biomimetic properties, such as molecular crowding and selective partitioning, make them promising components for designing cell-like materials. However, their use as artificial organelles has been limited by their complex molecular structure, limited control over internal microenvironment properties, and inherent colloidal instability. Here we report the design of dipeptide coacervates that exhibit enhanced stability, biocompatibility, and a hydrophobic microenvironment. The hydrophobic character facilitates the encapsulation of hydrophobic species, including transition metal-based catalysts, enhancing their efficiency in aqueous environments. Dipeptide coacervates carrying a metal-based catalyst are incorporated as active artificial organelles in cells and trigger an internal non-biological chemical reaction. The development of coacervates with a hydrophobic microenvironment opens an alternative avenue in the field of biomimetic materials with applications in catalysis and synthetic biology.

Polymeric Microreactors with pH-Controlled Spatial Localization of Cascade Reactions.

Lipid and polymer vesicles provide versatile means of creating systems that mimic the architecture of cells. However, these constructs cannot mimic the adaptive compartmentalization observed in cells, where the assembly and disassembly of subcompartments are dynamically modulated by environmental cues. Here, we describe a fully polymeric microreactor with a coacervate-in-vesicle architecture that exhibits an adaptive response to pH. The system was fabricated by microfluidic generation of semipermeable biomimetic polymer vesicles within 1 min using oleyl alcohol as the oil phase. The polymersomes allowed for the diffusion of protons and substrates acting as external signals. Using this method, we were able to construct adaptive microreactors containing internal polyelectrolyte-based catalytic organelles capable of sequestering and localizing enzymes and reaction products in a dynamic process driven by an external stimulus. This approach provides a platform for the rapid and efficient construction of robust adaptive microreactors that can be used in catalysis, biosensing, and cell mimicry.