Cryomicroneedle delivery of nanogold-engineered Rhodospirillum rubrum for photochemical transformation and tumor optical biotherapy

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 Rhodospirillum rubrum (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 R. rubrum 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 in situ 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. CryoMNs-R.r-Au employing cryomicroneedles for transdermal delivery of nanogold-engineered Rhodospirillum rubrum through optical biotherapy for remodeling the tumor microenvironment. Under laser irradiation, R.r-Au can effectively enhance lactate consumption and hydrogen production by photochemical transform through electron transfer into the photosynthetic system of R. rubrum, leading to an improved antitumor immune activation. [Display omitted] •The strategy of “charging” bacteria with a nano-materials is to boost the intracellular metabolism of matter and energy using the photosynthetic electron transport chain of R. rubrum to achieve photochemical transformation.•R.r-Au enlarged lactate consumption and hydrogen production through electron transfer into the photosynthetic system of R. rubrum under laser irradiation to improved tumor immune activation for tumor optical biotherapy.•The transdermal therapeutic cryomicroneedles patch as a minimally invasive delivery approach is employed to achieve safe and high-efficiency in situ microactive drug