Adoptive T _reg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome

Abstract

Regulatory T (T reg ) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T reg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local T reg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the T reg suppressive functions via the fatty acid oxidation (FAO)–mediated metabolic intervention. T reg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid–mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.

Ultrarapid‐Acting Microneedles for Immediate Delivery of Biotherapeutics

“…The release behavior of the FITC‐labeled LRT from the MN patch was observed by a fluorescence microscope and a confocal microscope. [ 18 ] Meanwhile, the gas production in URA‐MN at the initial release could be observed by a fluorescence microscope.…”

Microneedle‐Mediated Cell Therapy

“…Gu, Zhang, and coworkers developed perforated MNs to locally deliver Treg cells with augmented immune suppression to treat autoimmune disease in a representative psoriasis model (Figure 2d‐f). [ 26 ] The perforated MN was first formed by a “sandwich” molding method via squeezing the polymeric shell made of poly(vinyl propionate‐ co ‐methyl methacrylate) [poly(VP‐ co ‐MMA)] between the top and bottom polydimethylsiloxane (PDMS) molds. The ratio of VP and MMA was optimized to ensure the stiffness of the needle (0.376 N/needle).…”

“…[ 21–24 ] These challenges hinder the clinical translation of relevant cell therapy, especially for localized diseases such as solid tumors, skin disorders, and organ‐specific diseases. [ 25–28 ]…”

“…The assistance of MN in cell delivery could augment therapeutic effects through facilitating cell penetration and retention, enhancing tissue targeting, and reducing systematic toxicity. [ 25–26 ] The properties of representative MN systems are summarized in terms of fabrication methods, mechanical properties, cell loading capacity, as well as viability and bioactivity of the loaded cells. Finally, the key challenges and perspectives on future development of MN‐mediated cell therapy are also discussed.…”

Self‐Heating Multistage Microneedle Patch for Topical Therapy of Skin Cancer

“…[7] Its treatment methods mainly include surgical resection, radiotherapy, chemotherapy, immunotherapy, as well as topical medication. [8][9][10][11] Among them, topical therapy which directly delivers drugs to the targeted lesions has been a mainstay treatment for skin cancer and holds many advantages, including convenience, low side effects, affordability, and patient-directed DOI: 10.1002/adma.202308217 application. [12][13][14][15][16][17] Generally, topical medications for skin cancer are available in a large range of formulations such as lotions, ointments, creams, gels, liquids, pastes, foams, and patches.…”