AI Article Synopsis

  • Combining targeted therapy and immunotherapy shows potential for curing cancer through a novel biohybrid system using bacteria and layered double hydroxides (LDH).
  • The specially designed system reduces bacterial pathogenicity and enhances circulation, allowing bacteria to reach tumor sites where they convert nitrate to nitric oxide (NO) to induce tumor cell death.
  • Laboratory results indicate this approach effectively eliminates solid tumors, inhibits metastasis, and promotes immune responses, suggesting a promising direction for cancer treatment.

Article Abstract

Combining targeted therapy and immunotherapy brings hope for a complete cancer cure. Due to their selective colonization and immune activation capacity, some bacteria have the potential to realize targeted immunotherapy. Herein, a biohybrid system was designed and synthesized by cladding NO-intercalated cobalt aluminum layered double hydroxides (LDH) on anaerobic (PA) (PA@LDH). In this system, the covering of LDH reduces the pathogenicity of PA to normal tissues and alters its surface charge for prolonged in vivo circulation. Once the tumor site is reached, the acid-responsive degradation of LDH enables PA exposure. PA can colonize and convert nitrate ions to nitric oxide (NO) through denitrification. Then, NO reacts with intracellular O to produce toxic reactive nitrogen species ONOO and induce tumor cell apoptosis. In addition, cobalt ions released from LDH can inhibit the activity of superoxide dismutase (SOD), thus increasing the level of O and further enhancing the antitumor effect. Moreover, PA exposure activates M2-to-M1 macrophage polarization and a range of immune responses, thereby achieving a sustained antitumor activity. In vitro and in vivo results reveal that the biohybrid system eliminates solid tumors and inhibits tumor metastasis effectively. Overall, the biohybrid strategy provides a new avenue for realizing simultaneous immunotherapy and targeted therapy.

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Source
http://dx.doi.org/10.1021/acsami.3c08936DOI Listing

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