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 low treatment efficacy, 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 4-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 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.

Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy

“…6h , the most apparent tumor cell destruction, tissue necrosis and nuclear pyknosis are found in Trojan bacteria-treated group. As previously reported, the PPT-induced thermolysis of tumor cells would not affect the survival of neighboring non-tumor cells since the NIR light could precisely locate the tumor site, thereby minimizing the damage to surrounding normal tissue 19 , 30 , 32 , 33 , 38 , 39 , 48 . In addition, there was little difference between the trojan EC and VNP in terms of heating curve, fluorescence signal or survival time.…”

Current Status and Future Directions of Bacteria-Based Immunotherapy

“…Similarly, aptamers which promoted the colonization of bacteria inside tumor areas were also conjugated to S. typhimurium VNP20009 by Tan et al, which manifested excellent anti-tumor efficacy in 4T1 tumor-bearing mouse models. Moreover, the percentage of CD3 + CD4 + T cells and the production of IFN-g and TNF-a ware significantly elevated, suggesting strong immune response triggered by this bacterial agent (63). In another mouse model of triple negative breast cancer, impaired tumor growth and notable reduction in lung metastasis were reported in mice treated with E. coli encoding nanobody antagonist of CD47 (69).…”

“…In addition, an aptamer is an oligomeric nucleic acid that can specifically bind to a certain molecule and has similar ligand-receptor binding characteristics with the target molecule. By binding the aptamer AS1411 to the surface of S. typhimurium VNP20009, Geng et al observed nearly 2-fold and 4-fold enrichment after 12 and 60 hours in 4T1 and H22 tumorbearing mouse models compared to unmodified bacteria, showing the enhanced targeting performance of this bacterium(63).…”

Decorating Bacteria with Triple Immune Nanoactivators Generates Tumor‐Resident Living Immunotherapeutics

“…[5,22,23] We have recently exploited covalent conjugation, supramolecular interactions, and physical encapsulation to modify the bacterial surface and endow it with diverse extra functions. [24][25][26][27][28][29][30] Inspired by these achievements, we designed triple immune nanoactivators based on PDA nanoparticles conjugated with OVA antigen and α-PD-1 antibody and attached them to the bacterial surface by in situ interfacial polymerization using dopamine as a monomer.…”