Despite significant recent progress in nanomedicine, drug delivery to solid tumors remains a formidable challenge often associated with low delivery efficiency and limited penetration of the drug in poorly vascularized regions of solid tumors. Attenuated strains of facultative anaerobes have been demonstrated to have exceptionally high selectivity to primary tumors and metastatic cancer, a good safety profile, and superior intratumoral penetration performance. However, bacteria have rarely been able to completely inhibit tumor growth in immunocompetent hosts solely by their presence in the tumor. We have developed a Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) in which the functional capabilities of tumor-targeting bacteria are interfaced with chemotherapeutic-loaded nanoparticles, an approach that would amplify the therapeutic potential of both modalities. Here, we describe two biomanufacturing techniques to construct NanoBEADS by linking different bacterial species with polymeric theranostic vehicles. NanoBEADS are envisioned to significantly impact current practices in cancer theranostics through improved targeting and intratumoral transport properties.
Keywords: Bacteria; Bacteria-based therapy; Biomanufacturing; Cancer; Intratumoral transport; Nanoparticle; Self-assembly; Surface functionalization.