Nanocatalytic bacteria disintegration reverses immunosuppression of colorectal cancer

Han Jiang; Yuedong Guo; Zhiguo Yu; Ping Hu; Jianlin Shi

doi:10.1093/nsr/nwac169

Nanocatalytic bacteria disintegration reverses immunosuppression of colorectal cancer

Natl Sci Rev. 2022 Aug 29;9(11):nwac169. doi: 10.1093/nsr/nwac169. eCollection 2022 Nov.

Authors

Han Jiang^{1

2}, Yuedong Guo^{1

2}, Zhiguo Yu^{1

2}, Ping Hu^{1

3}, Jianlin Shi^{1

2

3}

Affiliations

¹ State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China.
² Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai 200092, China.

Abstract

Tumor-associated bacteria (TAB) play a critically important role in regulating the microenvironment of a tumor, which consequently greatly deteriorates the therapeutic effects by chemo- and radiotherapy deactivation and, more considerably, leads to substantial immunosuppression. On the contrary, herein we propose a nanocatalytic tumor-immunotherapeutic modality based on the bacteria disintegration by bacteria-specific oxidative damage under magnetic hyperthermia for highly effective immune response activation-promoted tumor regression. A monodispersed and superparamagnetic nanocatalytic medicine modified by arginyl-glycyl-aspartic acid (RGD) and (3-carboxypropyl)triphenylphosphonium bromide (TPP), named as MNP-RGD-TPP herein, has been synthesized, which features selective accumulation at the TAB by the electrostatic affinity, enabling effective TAB disintegration by the nanocatalytic Fenton reaction producing abundant cytotoxic hydroxyl radicals in situ under alternating magnetic field-induced hyperthermia. More importantly, the lipopolysaccharide has been metabolically secreted from the destructed TAB as pathogen-associated molecular patterns (PAMPs) to M1-polarize tumor-associated macrophages (TAMs) and promote the maturation of dendritic cells (DCs) for innate immuno-response activation of TAMs, followed by cytotoxic T lymphocytes awakening under the PAMPs presentation by the mature DCs against tumor cells. The integrated innate and adaptive immunity activations based on this TAB-promoted nanocatalytic immunomedicine, instead of magnetic heating-induced hyperthermia or the released Fe²⁺/Fe³⁺ Fenton agent, has been found to achieve excellent therapeutic efficacy in an orthotopic colorectal cancer model, demonstrating the great potential of such an integrated immunity strategy in clinical tumor immunotherapy.

Keywords: colorectal cancer immunotherapy; immunosuppressive reversal; nanocatalytic bacteria disintegration; tumor-associated bacteria.