Cell and fluid sampling microneedle patches for monitoring skin-resident immunity.

Important cell populations reside within tissues and are not accessed by traditional blood draws used to monitor the immune system. To address this issue at an essential barrier tissue, the skin, we created a microneedle-based technology for longitudinal sampling of cells and interstitial fluid, enabling minimally invasive parallel monitoring of immune responses. Solid microneedle projections were coated by a cross-linked biocompatible polymer, which swells upon skin insertion, forming a porous matrix for local leukocyte infiltration. By embedding molecular adjuvants and specific antigens encapsulated in nanocapsules within the hydrogel coating, antigen-specific lymphocytes can be enriched in the recovered cell population, allowing for subsequent detailed phenotypic and functional analysis. We demonstrate this approach in mice immunized with a model protein antigen or infected in the skin with vaccinia virus. After vaccination or infection, sampling microneedles allowed tissue-resident memory T cells (TRMs) to be longitudinally monitored in the skin for many months, during which time the antigen-specific T cell population in systemic circulation contracted to low or undetectable counts. Sampling microneedles did not change the immune status of naïve or antigen-exposed animals. We also validated the ability of cell sampling using human skin samples. This approach may be useful in vaccines and immunotherapies to temporally query TRM populations or as a diagnostic platform to sample for biomarkers in chronic inflammatory and autoimmune disorders, allowing information previously accessible only via invasive biopsies to be obtained in a minimally invasive manner from the skin or other mucosal tissues.

Synthetic Lift-off Polymer beneath Layer-by-Layer Films for Surface-Mediated Drug Delivery.

A broad range of biomaterials coatings and thin film drug delivery systems require a strategy for the immobilization, retention, and release of coatings from surfaces such as patches, inserts, and microneedles under physiological conditions. Here we report a polymer designed to provide a dynamic surface, one that first functions as a platform for electrostatic thin film assembly and releases the film once in an in vivo environment. Atom transfer radical polymerization (ATRP) was used to synthesize this polymer poly(o-nitrobenzyl-methacrylate-co-hydroxyethyl-methacrylate-co-poly(ethylene-glycol)-methacrylate) (PNHP), embedded beneath multilayered polyelectrolyte films. Such a base layer is designed to photochemically pattern negative charge onto a solid substrate, assist deposition of smooth layer-by-layer (LbL) polyelectrolyte in mildly acidic buffers and rapidly dissolve at physiological pH, thus lifting off the LbL films. To explore potential uses in the biomedical field, a lysozyme (Lys)/poly(acrylic acid) (PAA) multilayer film was developed on PNHP-coated silicon wafers to construct prototype antimicrobial shunts. Film thickness was shown to grow exponentially with increasing deposition cycles, and effective drug loading and in vitro release was confirmed by the dose-dependent inhibition of Escherichia coli (E. coli) growth. The efficacy of this approach is further demonstrated in LbL-coated microscale needle arrays ultimately of interest for vaccine applications. Using PNHP as a photoresist, LbL films were confined to the tips of the microneedles, which circumvented drug waste at the patch base. Subsequent confocal images confirmed rapid LbL film implantation of PNHP at microneedle penetration sites on mouse skin. Furthermore, in human skin biopsies, we achieved efficient immune activation demonstrated by a rapid uptake of vaccine adjuvant from microneedle-delivered PNHP LbL film in up to 37% of antigen-presenting cells (APC), providing an unprecedented LbL microneedle platform for human vaccination.

Koch Institute Symposium on Cancer Immunology and Immunotherapy.

The 12th annual summer symposium of The Koch Institute for Integrative Cancer Research at MIT was held in Cambridge, MA, on June 14th, 1023. The symposium entitled "Cancer Immunology and Immunotherapy" focused on recent advances in preclinical research in basic immunology and biomedical engineering, and their clinical application in cancer therapies. The day-long gathering also provided a forum for discussion and potential collaborations between engineers and clinical investigators. The major topics presented include: (i) enhancement of adoptive cell therapy by engineering to improve the ability and functionality of T-cells against tumor cells; (ii) current therapies using protein and antibody therapeutics to modulate endogenous anti-tumor immunity; and (iii) new technologies to identify molecular targets and assess therapeutic efficacy, and devices to control and target drug delivery more effectively and efficiently.