Polymerization‐Mediated Multifunctionalization of Living Cells for Enhanced Cell‐Based Therapy

Abstract

Recent discoveries in cell biology and microbiology have spotlighted the increasing importance of cell-based therapy, which offers the potential of altering and treating the course of diseases that cannot be addressed sufficiently by existing pharmaceuticals. [1,2] The use of living cells, including transfusion of hematopoietic stem cells, chimeric antigen receptor T-cell therapy, and fecal microbiota transplantation, has been successful in treating a multitude of intractable diseases, such as, congenital defects, cancers, and inflammatory bowel disease. [3,4] Unfortunately, cells are often fragile to unfriendly environmental stressors, such as, temperature fluctuation and centrifugation encountered during preparation, as well as, host immune system and metabolic microenvironment suffered after transplantation, leading to unwanted cell death and a decline in therapeutic efficacy. [5,6] In addition, monomodal therapy always results in inadequately therapeutic response due largely to the complexity of cellular interactions and the multiplicity of cell targets. [7] Therefore, methods capable of simultaneously incorporating with a protection role and endowing with multiple therapeutic modalities are highly desirable to engineer satisfied cells for enhanced cell-based therapy. Surface decoration of living cells, which attaches functional motifs to cell surface, provides a unique tool for generating engineered cells, in a programmed manner, with exogenous characteristics that are neither inherent nor naturally achievable. [8] Particularly, a variety of elegant approaches have been developed to wrap cells chemically with synthetic cytoprotective coatings, forming a cell-in-shell structure. [9-14] For example, a number of mammalian cells have been encapsulated individually with polymers, silica, and calcium phosphate to enhance viability by protecting cells from external aggressors during manipulation, handling, and storage. [12-15] As a representative of fungi, yeast cells have been embedded within a complex of pyrogallol and Fe(III)-tannic acid to improve the tolerance against environmental attacks. [16] Recently, we have encased probiotics with biological membranes to protect bacteria from lethal factors in real-life settings. [17-20] For instance, a beneficial bacterium camouflaged with an erythrocyte membrane exhibits an immunogenic shielding effect, which reduces their clearance by macrophages. [17] However, conventional surface decoration involves tedious complicated fabrication and has limited Surface decoration of living cells by exogenous substances offers a unique tool for understanding and tuning cell behaviors, which plays a critical role in cell-based therapy. Here, a facile yet versatile approach for decorating individual living cells with multimodal coatings is reported. By simply co-depositing with dopamine under a cytocompatible condition, various functional small molecules and polymers can be encoded to form a multifunctional coating on a cell's surface. The accessibility and versatility of this method...

Decorating Bacteria with a Therapeutic Nanocoating for Synergistically Enhanced Biotherapy

“…It was worth noting that both preparation procedure and nanocoating on bacterial surface presented negligible influence on the viability of coated EcN, which was critical for developing microecologics. [32] As demonstrated in Figure 4A and Table S1 (Supporting Information), SEcN 4 appeared a similar growth profile to that of uncoated bacteria, indicating that silk fibroin coating had limited influence on the viability and proliferation of coated bacteria. Orally administered probiotics firstly undergo threats associated with digestive fluids in gastric cavity and early intestinal intraluminal environment before colonization in the intestine.…”

“…[28,29] Recently, we have wrapped with various coatings to increase bacterial survival and colonization in vivo following administration. [30][31][32][33] For instance, coating probiotic bacteria with lipid membranes can strengthen bacterial viability under unfriendly environments, particularly the insults of acids and enzymes in gastric fluid, which largely improves their bioavailability after oral ingestion. [20] However, previous surface decorations attempting to wrap bacteria with an entire coating only involve protective roles and are unable to confer additional therapeutic advantages on the coated bacteria.…”

Super‐Strong and Super‐Stiff Chitosan Filaments with Highly Ordered Hierarchical Structure

“…In addition, the 13 C NMR spectrum (Figure 2c) of the chitin powder showed eight characteristic resonances at 173.5 ppm for CO, 104.2 ppm for C1, 83.2 ppm for C4, 75.8 ppm for C5, 73.5 ppm for C3, 60.8 ppm for C6, 55.3 ppm for C2, and 22.9 ppm for the CH 3 group of α-chitin crystals. [41,44,45] In the case of the chitosan powder, the carbon resonance of C2, which are primarily involved in hydrogen bonding interactions with glucosamine units, shifted downfield by 3.1 ppm.…”

“…These organisms produce ≈100 billion t/a of chitin through biosynthesis. [10] As the most important deacetylated derivative of chitin, chitosan has great potential for applications in biomaterials, [11][12][13] tissue engineering, [14][15][16][17] water treatment, [18,19] and agri-tech revolution [20] owing to its high chemical reactivity, excellent antibacterial activity, biocompatibility, and biodegradability. With the rapidly increasing demand for fiber materials, the development of highperformance biomass-based fibers has become an important research topic to reduce our reliance on petroleum-based synthetic fibers.…”

Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

“…[16][17][18][19] We have recently wrapped with extra coatings to retain bacterial viability under unfriendly external conditions. [20][21][22][23][24] For instance, bacteria decorated with a stealth coating can decrease their elimination by macrophages, which subsequently prolongs blood circulation following systemic injection. [25] However, previous modifications by both chemical and genetical approaches lack the ability to endow bacteria with increment in tumor-specific localization after administration.…”