Microfluidic production and characterization of biofunctionalized giant unilamellar vesicles for targeted intracellular cargo delivery

Staufer, Oskar; Antona, Silvia; Zhang, Dennis; Csatári, Júlia; Schröter, Martin; Janiesch, Jan-Willi; Fabritz, Sebastian; Berger, Imre; Platzman, Ilia; Spatz, Joachim P.

doi:10.1016/j.biomaterials.2020.120203

Cited by 55 publications

(78 citation statements)

References 49 publications

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“…Spatz and coworkers recently presented another approach, starting with copolymer-stabilized droplets to generate liposomes, termed droplet-stabilized GUVs [41]. When combined with a droplet splitting technique, an impressive production rate of >10 6 GUVs/min was reported [42]. Overall, on-chip GUV production is a promising approach, especially in terms of sample monodispersity and encapsulation efficiency.…”

Section: Open Accessmentioning

confidence: 99%

(R)evolution-on-a-chip

Bouzetos

Ganar

Mastrobattista

et al. 2022

Trends in Biotechnology

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Section: Open Accessmentioning

confidence: 99%

(R)evolution-on-a-chip

Bouzetos

Ganar

Mastrobattista

et al. 2022

Trends in Biotechnology

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“…For instance, microfluidic approaches have been developed for the assembly of synthetic cells with adjustable and tunable composition. Specifically, water-in-oil droplets as cell-iszed compartments are generated and their lumen is filled with proteins, lipids or nucleic acids, providing means to engineer systems capable of genetic information processing and artificial genotype-to-phenotype coupling 23,[44][45][46][47] .…”

Section: Recent Research Directions and Bottlenecksmentioning

confidence: 99%

Building a community to engineer synthetic cells and organelles from the bottom-up

Staufer

Lora

Bailoni³

et al. 2021

Preprint

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Empowered by emerging concepts from physics, chemistry, and bioengineering, learning-by-building approaches have found increasing application in the life sciences. Particularly, they are directed to tackle the overarching goal of engineering cellular life from scratch. The SynCell2020/21 conference brought together a diverse group of researchers to share progress and chart the course of this field. Participants identified key steps to design, manipulate, and create cell-like entities, especially those with hierarchical organization and function. This article highlights achievements in the field, including areas where synthetic cells are having socioeconomic and technological impact. Guided by input from early-career researchers, we identify challenges and opportunities for basic science and technological applications of synthetic cells. A key conclusion is the need to build an integrated research community through enhanced communication, resource-sharing, and educational initiatives. Development of an international and interdisciplinary community will enable transformative outcomes and attract the brightest minds to contribute to the field.

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“…These observations show that micron-scale lipid carriers, such as giant unilamellar vesicles (GUVs), might have great potential for primary targeting. An additional advantage of micronscale lipid-based vehicles is that the cell-carrier interaction can be modulated by incorporating various ligands, or repellant motifs, while also incorporating stimulus-sensitive motives for improved fusogenicity and internalization [20]. Moreover, several recent studies have demonstrated that micron-scale lipid-based vesicles can interact with cells and their intracellular components [21] as well as directly release therapeutics inside the cytoplasm [22].…”

mentioning

confidence: 99%

“…Such a paradigm shift from nano-to micron-sized materials would also allow the utilization of microfluidic technologies (Figure 2, Key Figure) that offer the notable advantages of excellent reproducibility, controllability, complexity, and production capability. In particular, droplet-based microfluidics is ideally suited to engineer micron-scale complex lipid vesicles through sequential and precise manipulation of water-in-oil droplets [20,21,[24][25][26].…”

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confidence: 99%

Can Bottom-Up Synthetic Biology Generate Advanced Drug-Delivery Systems?

Lussier

Staufer

Platzman

et al. 2021

Trends in Biotechnology

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Creating a magic bullet that can selectively kill cancer cells while sparing nearby healthy cells remains one of the most ambitious objectives in pharmacology. Nanomedicine, which relies on the use of nanotechnologies to fight disease, was envisaged to fulfill this coveted goal. Despite substantial progress, the structural complexity of therapeutic vehicles impedes their broad clinical application. Novel modular manufacturing approaches for engineering programmable drug carriers may be able to overcome some fundamental limitations of nanomedicine. We discuss how bottom-up synthetic biology principles, empowered by microfluidics, can palliate current drug carrier assembly limitations, and we demonstrate how such a magic bullet could be engineered from the bottom up to ultimately improve clinical outcomes for patients. Drug-Delivery Challenges: Opportunities for Bottom-Up Synthetic BiologyPaul Ehrlich, considered to be the pioneer and founder of modern chemotherapy, envisaged a therapeutic capable of directly interreacting with its intended disease-causing cellular structure while remaining harmless to the surrounding healthy cell population. Depicted as a magic bullet, his idea has greatly influenced and fascinated various fields of science for more than a century [1]. Among them, the field of nanomedicine (see Glossary)which relies on nanotechnologies to improve passive and active accumulation of drugs nearby target pathogens or cell populationswas expected to achieve this highly coveted goal. Despite its major focus on oncology, nanomedicine has also triggered the engineering of an arsenal of novel nanotechnologies and functionalization strategies. Overall, these innovations have resulted in a variety of enhanced bio-and physico-chemical properties for inorganic-, polymer-, and lipid-based nanometric carriers.Despite recent progress, nanomedicine is often synonymous with modest clinical translation and remains the focus of significant debate (as reviewed extensively [2-4]). Isolated examples of success, namely Doxil® [5,6], Abraxane® [7], and most recently Onpattro® [8], are few, and greater success in the design of nanoformluated drugs in the near future remains unlikely because several barriers will need to be overcome to achieve effective and specific delivery of drug-loaded carriers.Targeted delivery of therapeutics may be organized into different levels, referred to as primary, secondary, and tertiary targeting. These levels are defined by the degree of target specificity and control over release dynamics, which increase along the chain [9]. This targeting hierarchy is summarized and illustrated in Boxes 1 and 2, and also in Figure 1. Briefly, primary targeting, or the targeting of specific organs, is highly size-dependent since smaller nanomaterials are expected to transit through the blood-brain barrier [10][11][12], or navigate through the fenestrated vessels in the liver endothelium or tumor environment more easily [13]. However, this size discrimination may be circumvented by meticulously engineering t...

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Microfluidic production and characterization of biofunctionalized giant unilamellar vesicles for targeted intracellular cargo delivery

Cited by 55 publications

References 49 publications

(R)evolution-on-a-chip

(R)evolution-on-a-chip

Building a community to engineer synthetic cells and organelles from the bottom-up

Can Bottom-Up Synthetic Biology Generate Advanced Drug-Delivery Systems?

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