Cryomicroneedle delivery of nanogold-engineered <i>Rhodospirillum rubrum</i> for photochemical transformation and tumor optical biotherapy.

Abstract

Tumor metabolite regulation is intricately linked to cancer progression. Because lactate is a characteristic metabolite of the tumor microenvironment (TME), it supports tumor progression and drives immunosuppression. In this study, we presented a strategy for antitumor therapy by developing a nanogold-engineered <i>Rhodospirillum rubrum</i> (R.r-Au) that consumed lactate and produced hydrogen for optical biotherapy. We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles (CryoMNs) patch integrated with R.r-Au to efficiently deliver living bacterial drugs. Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%. We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin. In addition, it rapidly dissolved after administering bacterial drugs and did not produce by-products. Under laser irradiation, R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of <i>R. rubrum</i> and enlarged lactate consumption and hydrogen production, thus leading to an improved tumor immune activation. Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive <i>in situ</i> delivery approach for living bacterial drugs. This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.