Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

Abstract

Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by severe side effects and low treatment efficacies, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers. Optimal bacteria conjugated with an average of 2.8 × 105 aptamers per cell present the highest specificity to tumor cells in vitro, separately generating near 2- and 5-times higher accumulation in tumor tissue at 12 and 60 hours compared to unmodified bacteria. In both 4T1 and H22 tumor-bearing mouse models, aptamer-conjugated attenuated Salmonella show strikingly enhanced antitumor efficacy, along with highly activated immune responses inside the tumor. This work demonstrates how bacterial behaviors can be tuned by surface conjugation and supports the potential of aptamer-conjugated bacteria for both targeted intratumoral localization and enhanced tumor biotherapy.

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

“…Different strategies have been established recently to enhance the therapeutic efficacy of bacteria by increasing their bioactivity, survival in the biological milieu, safety, and targeting properties. Strategies documented to date include mainly surface functionalization [2,3], protection and activation by diverse materials [4][5][6], and modification for controlling intra-tumoral drug distribution [7]. As drug carriers, bacteria proved to effectively deliver therapeutic agents for treating cancer and other conditions [7][8][9].…”

Enhancing Gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments antitumor immune response

“…Moreover, both in the 4T1 tumor model and B16F10 tumor model, the body weight of the mice showed no significant decrease after the treatment of the hydrogel-based delivery systems (Supplementary Figs. 21,22). In addition, H&E assay of the major organs in the C57BL6 mice further demonstrated a good biosafety profile of the hydrogel-based delivery system (Supplementary Fig.…”

“…Moreover, the abundant flagella of VNP could activate the caspase 1 to transform the delivered GSDMD proteins into the active form for triggering tumor cell pyroptosis. After removing extra linkers by ultrafiltration, the GSDMD protein cages were conjugated on the surface of VNP by a facile amide reaction 21 . The obvious particle protrusions were visualized on the surface of the modified bacteria under transmission electron microscope (TEM) imaging (Fig.…”

Cholesterol removal significantly improves performance of a model anti-tumor biomimetic nano delivery system integrating immunotherapy and STING activation

“…Clearly, this strategy may also be used for other medical conditions other than cancer (Figure S10), such as improving the targeting of neutrophil membrane-coated nanoparticles to arthritis 47 , or achieving long-term controlled release in blood 48 . Different delivery vehicles, such as bacteria, could be coated to suppress immune surveillance and enhance the enrichment of bacteria in target sites 49,50 .…”