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Literatures



https://pubs.rsc.org/en/content/articlelanding/2015/sc/c5sc02479j#!divAbstract

New chemosynthetic route to linear ε-poly-lysine


ε-Poly-lysine (ε-PL) is an uncommoncationic, naturally-occurring homopolymer produced by the fermentation process. Due to its significant antimicrobial activity and nontoxicity to humans, ε-PL is now industrially produced as an additive, e.g. for food and cosmetics. However, the biosynthetic route can only make polymers with a molecular weightof about 3 kDa. Here, we report a new chemical strategy based on ring-opening polymerization (ROP) to obtain ε-PL from lysine. The 2,5-dimethylpyrrole protected α-amino-ε-caprolactam monomer was prepared through cyclization of lysine followed by protection. ROP of this monomer, followed by the removal ofthe protecting group, 2,5-dimethylpyrrole, ultimately yielded ε-PL with varying molecular weights. The structure of this chemosynthetic ε-PL has been fully characterized by 1H NMR, 13C NMR, and MALDI-TOF MS analyses. This chemosynthetic ε-PL exhibited a similar pKa value and low cytotoxicity as the biosynthetic analogue. Using this new chemical strategy involving ROP without the need for phosgene may enable a more cost effective production of ε-PL on a larger-scale, facilitating the design of more advanced biomaterials.



https://doi.org/10.1016/j.bej.2012.04.001

Review on production and medical applicationsof ɛ-polylysine

ɛ-Polylysine (ɛ-PL) is a homopolyamide linked by the peptide bond between the carboxylic and epsilon amino group of adjacent lysine molecules. It is naturally occurring biodegradable and nontoxic towards human. This review article gives an insight about the various ɛ-PL producing strains, their screening procedures, mechanism of synthesis, characterization, and its application in the medical field. The polycationic nature of ɛ-PL at physiological pH makes it as one of the potential candidates in the field of drug delivery. Most of the biomedical applications till date use synthetic α-PLL as a raw material. However, it is believed that naturally occurring ɛ-PL would be an ideal substitute.



http://cshprotocols.cshlp.org/content/2012/4/pdb.prot068627.abstract

In Vitro Transfection with Plasmid DNA Using Polylysine Copolymers

SungWan Kim

Adapted from Gene Transfer: Delivery and Expression of DNA and RNA (ed. Friedmann and Rossi). CSHL Press, ColdSpring Harbor, NY, USA, 2007.

Abstract

The terplex system for delivering DNA to targeted cells comprises three components—stearyl polylysine (PLL), low-densitylipoprotein (LDL), and DNA. This article describes a method for optimizing the relative amounts of these components and determining the transfection parameters for a given cell line.



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500703/

Synthetic alternatives to Matrigel

Matrigel, a basement-membrane matrix extracted from Engelbreth–Holm–Swarm mouse sarcomas, has been used for more than four decades for a myriad of cell culture applications. However, Matrigelis limited in its applicability to cellular biology, therapeutic cell manufacturing and drug discovery owing to its complex, ill-defined and variable composition. Variations in the mechanical and biochemical properties within a single batch of Matrigel — and between batches — have led to uncertainty in cell culture experiments and a lack of reproducibility. Moreover, Matrigel is not conducive to physical or biochemical manipulation, making it difficult to fine-tune the matrix to promote intended cell behaviours and achieve specific biological outcomes. Recent advances in synthetic scaffolds have led to the development of xenogenic-free, chemically defined, highly tunable and reproducible alternatives.



Towards organoid culture without Matrigel

https://www.nature.com/articles/s42003-021-02910-8

Organoidscellular aggregates derived from stem or progenitor cells that recapitulate organ function in miniature—are of growing interest in developmental biology and medicine. Organoids have been developed for organs and tissues such as the liver, gut, brain, and pancreas; they are used as organ surrogates to study a wide range of questions in basic and developmental biology, genetic disorders, and therapies. However, many organoids reported to date have been cultured in Matrigel, which is prepared from the secretion of Engelbreth-Holm-Swarm mouse sarcoma cells; Matrigel is complex and poorly defined. This complexity makes it difficult to elucidate Matrigel-specific factors governing organoid development.



Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases

https://pubmed.ncbi.nlm.nih.gov/29563317/

Abstract

Cancer immunotherapy can confer durablebenefit, but the percentage of patients who respond to this approach remainsmodest. The ability to concentrate immunostimulatory compounds at the site ofdisease can overcome local immune tolerance and reduce systemic toxicity.Surgical resection of tumors may improve the efficacy of immunotherapy byremoving the concentrated immunosuppressive microenvironment; however, it alsoremoves tumor-specific leukocytes as well as tumor antigens that may beimportant to establishing antitumor immunity. Moreover, surgery produces atransient immunosuppressive state associated with wound healing that has beencorrelated with increased metastasis. Using multiple models of spontaneousmetastasis, we show that extended release of agonists of innateimmunity-including agonists of Toll-like receptor 7/8 (TLR7/8) or stimulator ofinterferon genes (STING)-from a biodegradable hydrogel placed in the tumorresection site cured a much higher percentage of animals than systemic or localadministration of the same therapy in solution. Depletion and neutralizationexperiments confirmed that the observed prevention of local tumor recurrenceand eradication of existing metastases require both the innate and adaptivearms of the immune system. The localized therapy increased the numbers ofactivated natural killer (NK) cells, dendritic cells, and T cells and inducedproduction of large amounts of type I interferons, thereby converting animmunosuppressive post-resection microenvironment into an immunostimulatoryone. The results suggest that the perioperative setting may prove to be auseful context for immunotherapy, particularly when the release of the therapyis extended locally.





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