Suh, SeungBeum Jo, Ami Traore, Mahama A. Zhan, Ying Coutermarsh-Ott, Sheryl L. Ringel-Scaia, Veronica M. Allen, Irving C. Davis, Richey M. Behkam, Bahareh 2024-01-19T20:34:41Z 2024-01-19T20:34:41Z 2021-09-02 2019-02-06 2198-3844 https://pubs.kist.re.kr/handle/201004/120361 Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria-enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor-targeting S. Typhimurium VNP20009 are interfaced with poly(lactic-co-glycolic-acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self-replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100-fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects. English WILEY SALMONELLA-TYPHIMURIUM TUMOR SPHEROIDS CANCER-THERAPY ENTERICA NANOPARTICLES BIODISTRIBUTION SECRETION BARRIERS EFFICACY INVASION Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine Article 10.1002/advs.201801309 1 ADVANCED SCIENCE, v.6, no.3 ADVANCED SCIENCE 6 3 scie scopus 000458118100010 2-s2.0-85057766306 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article SALMONELLA-TYPHIMURIUM TUMOR SPHEROIDS CANCER-THERAPY ENTERICA NANOPARTICLES BIODISTRIBUTION SECRETION BARRIERS EFFICACY INVASION bacteria-based therapies biohybrid systems extravascular transport intratumoral penetration Salmonella enterica serovar Typhimurium tumor-targeting bacteria