Targeting the Tumor Microbiota in Cancer Therapy Basing on Nanomaterials

Abstract

Intra-tumoral microbiota, which is a potential component of the tumor microenvironment (TME), has been emerging as a key participant and driving factor in cancer. Previously, due to technical issues and low biological content, little was known about the microbial community within tumors. With the development of high-throughput sequencing technology and molecular biology techniques, it has been demonstrated that tumors harbor highly heterogeneous symbiotic microbial communities, which affect tumor progression mechanisms through various pathways, such as inducing DNA damage, activating carcinogenic pathways, and inducing an immunesuppressive environment. Faced with the harmful microbial communities in the TME, efforts have been made to develop new technologies specifically targeting the microbiome and tumor microecology. Given the success of nanotechnology in cancer diagnosis and treatment, the development of nanotechnology to regulate microscale and molecular-scale interactions occurring in the microbiome and tumor microecology holds promise for providing new approaches for cancer therapy. This article reviews the latest progress in this field, including the microbial community within tumors and its pro-cancer mechanisms, as well as the anti-tumor strategies targeting intra-tumoral microorganisms using nanotechnology. Additionally, this article delivers prospects for the potential clinical significance and challenges of anti-tumor strategies against intra-tumoral microorganisms.

Keywords

antibacterial / intra-tumoral microbiota / nanomaterials / tumor therapy

References

[1] Y. Xiao and D. Yu, “Tumor Microenvironment as a Therapeutic Target in Cancer,” Pharmacology & Therapeutics 221 (2021): 107753.

[2] N. Gagliani, B. Hu, S. Huber, E. Elinav, and R. A. Flavell, “The Fire Within: Microbes Inflame Tumors,” Cell 157 (2014): 776.

[3] D. Chrysostomou, L. A. Roberts, J. R. Marchesi, and J. M. Kinross, “Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy,” Gastroenterology 164 (2023): 198.

[4] R. Gao, C. Kong, L. Huang, et al., “Mucosa-Associated Microbiota Signature in Colorectal Cancer,” European Journal of Clinical Microbiology & Infectious Diseases 36 (2017): 2073.

[5] K. L. Greathouse, J. R. White, A. J. Vargas, et al., “Interaction Between the Microbiome and TP53 in Human Lung Cancer,” Genome Biology 19 (2018): 123.

[6] A. Papakonstantinou, P. Nuciforo, M. Borrell, et al., “The Conundrum of Breast Cancer and Microbiome—A Comprehensive Review of the Current Evidence,” Cancer Treatment Reviews 111 (2022): 102470.

[7] A. T. F. Choy, I. Carnevale, S. Coppola, et al., “The Microbiome of Pancreatic Cancer: From Molecular Diagnostics to New Therapeutic Approaches to Overcome Chemoresistance Caused by Metabolic Inactivation of Gemcitabine,” Expert Review of Molecular Diagnostics 18 (2018): 1005.

[8] L. T. Geller, M. Barzily-Rokni, T. Danino, et al., “Potential Role of Intratumor Bacteria in Mediating Tumor Resistance to the Chemotherapeutic Drug Gemcitabine,” Science 357 (2017): 1156.

[9] N. Cullin, C. Azevedo Antunes, R. Straussman, C. K. Stein-Thoeringer, and E. Elinav, “Microbiome and Cancer,” Cancer Cell 39 (2021): 1317.

[10] Y. A. Yu, S. Shabahang, T. M. Timiryasova, et al., “Visualization of Tumors and Metastases in Live Animals With Bacteria and Vaccinia Virus Encoding Light-Emitting Proteins,” Nature Biotechnology 22 (2004): 313.

[11] A. D. Kostic, E. Chun, L. Robertson, et al., “Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment,” Cell Host & Microbe 14 (2013): 207.

[12] E. M. Park, M. Chelvanambi, N. Bhutiani, G. Kroemer, L. Zitvogel, and J. A. Wargo, “Targeting the Gut and Tumor Microbiota in Cancer,” Nature Medicine 28 (2022): 690.

[13] G. Roviello, L. F. Iannone, M. Bersanelli, E. Mini, and M. Catalano, “The Gut Microbiome and Efficacy of Cancer Immunotherapy,” Pharmacology & Therapeutics 231 (2022): 107973.

[14] D. Hanahan, “Hallmarks of Cancer: New Dimensions,” Cancer Discovery 12 (2022): 31.

[15] Y. Jin, Y. Huang, H. Ren, et al., “Nano-Enhanced Immunotherapy: Targeting the Immunosuppressive Tumor Microenvironment,” Biomaterials 305 (2024): 122463.

[16] M. Osman, S. Budree, C. R. Kelly, P. Panchal, J. R. Allegretti, and Z. Kassam, “Effectiveness and Safety of Fecal Microbiota Transplantation for Clostridioides difficile Infection: Results from a 5344-Patient Cohort Study,” Gastroenterology 163 (2022): 319.

[17] R. L. Vincent, C. R. Gurbatri, F. Li, et al., “Probiotic-Guided CAR-T Cells for Solid Tumor Targeting,” Science 382 (2023): 211.

[18] N. Zhao, L. Yan, X. Zhao, et al., “Versatile Types of Organic/Inorganic Nanohybrids: From Strategic Design to Biomedical Applications,” Chemical Reviews 119 (2019): 1666.

[19] N. A. Scott, A. Andrusaite, P. Andersen, et al., “Antibiotics Induce Sustained Dysregulation of Intestinal T Cell Immunity by Perturbing Macrophage Homeostasis,” Science Translational Medicine 10, no. 464 (2018): eaao4755.

[20] Y. Dai, C. Xu, X. Sun, and X. Chen, “Nanoparticle Design Strategies for Enhanced Anticancer Therapy by Exploiting the Tumour Microenvironment,” Chemical Society Reviews 46 (2017): 3830.

[21] M. G. Dominguez-Bello, F. Godoy-Vitorino, R. Knight, and M. J. Blaser, “Role of the Microbiome in Human Development,” Gut 68 (2019): 1108.

[22] A. Wong-Rolle, H. K. Wei, C. Zhao, and C. Jin, “Unexpected Guests in the Tumor Microenvironment: Microbiome in Cancer,” Protein Cell 12 (2021): 426.

[23] S. Thomas, J. Izard, E. Walsh, et al., “The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists,” Cancer Research 77 (2017): 1783.

[24] P. S. Salvi and R. A. Cowles, “Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease,” Cells 10, no. 7 (2021): 1775.

[25] R. Sender, S. Fuchs, and R. Milo, “Revised Estimates for the Number of Human and Bacteria Cells in the Body,” PLoS Biology 14 (2016): e1002533.

[26] J. Chen, J. Douglass, V. Prasath, et al., “The Microbiome and Breast Cancer: A Review,” Breast Cancer Research and Treatment 178 (2019): 493.

[27] B. A. Helmink, M. A. W. Khan, A. Hermann, V. Gopalakrishnan, and J. A. Wargo, “The Microbiome, Cancer, and Cancer Therapy,” Nature Medicine 25 (2019): 377.

[28] B. Flemer, D. B. Lynch, J. M. Brown, et al., “Tumour-Associated and Non-Tumour-Associated Microbiota in Colorectal Cancer,” Gut 66 (2017): 633.

[29] C. C. Wong and J. Yu, “Gut Microbiota in Colorectal Cancer Development and Therapy,” Nature Reviews Clinical Oncology 20 (2023): 429.

[30] B. K. Perler, E. S. Friedman, and G. D. Wu, “The Role of the Gut Microbiota in the Relationship Between Diet and Human Health,” Annual Review of Physiology 85 (2023): 449.

[31] B. Flemer, R. D. Warren, M. P. Barrett, et al., “The Oral Microbiota in Colorectal Cancer Is Distinctive and Predictive,” Gut 67 (2018): 1454.

[32] W. Liu, X. Zhang, H. Xu, et al., “Microbial Community Heterogeneity Within Colorectal Neoplasia and Its Correlation with Colorectal Carcinogenesis,” Gastroenterology 160 (2021): 2395.

[33] S. Yachida, S. Mizutani, H. Shiroma, et al., “Metagenomic and Metabolomic Analyses Reveal Distinct Stage-Specific Phenotypes of the Gut Microbiota in Colorectal Cancer,” Nature Medicine 25 (2019): 968.

[34] A. D. Kostic, D. Gevers, C. S. Pedamallu, et al., “Genomic Analysis Identifies Association of Fusobacterium With Colorectal Carcinoma,” Genome Research 22 (2012): 292.

[35] C. A. Brennan, G. Nakatsu, C. A. Gallini Comeau, et al., “Aspirin Modulation of the Colorectal Cancer-Associated Microbe Fusobacterium nucleatum,” MBio 12, no. 2 (2021): e00521-e00547.

[36] J. Yu, Y. Chen, X. Fu, et al., “Invasive Fusobacterium nucleatum May Play a Role in the Carcinogenesis of Proximal Colon Cancer Through the Serrated Neoplasia Pathway,” International Journal of Cancer 139 (2016): 1318.

[37] S. Bullman, C. S. Pedamallu, E. Sicinska, et al., “Analysis of Fusobacterium Persistence and Antibiotic Response in Colorectal Cancer,” Science 358 (2017): 1443.

[38] S. F. Moss, S. C. Shah, M. C. Tan, and H. B. El-Serag, “Evolving Concepts in Helicobacter pylori Management,” Gastroenterology 166 (2024): 267.

[39] J. Wang, Y. Wang, Z. Li, X. Gao, and D. Huang, “Global Analysis of Microbiota Signatures in Four Major Types of Gastrointestinal Cancer,” Frontiers in Oncology 11 (2021): 685641.

[40] O. O. Coker, Z. Dai, Y. Nie, et al., “Mucosal Microbiome Dysbiosis in Gastric Carcinogenesis,” Gut 67 (2018): 1024.

[41] R. Peng, S. Liu, W. You, et al., “Gastric Microbiome Alterations Are Associated With Decreased CD8+ Tissue-Resident Memory T Cells in the Tumor Microenvironment of Gastric Cancer,” Cancer Immunology Research 10 (2022): 1224.

[42] C. B. Zhou, S. Y. Pan, P. Jin, et al., “Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer,” Gastroenterology 162 (2022): 1933.

[43] J. J. Tsay, B. G. Wu, M. H. Badri, et al., “Airway Microbiota Is Associated With Upregulation of the PI3K Pathway in Lung Cancer,” American Journal of Respiratory and Critical Care Medicine 198 (2018): 1188.

[44] E. A. Grice, H. H. Kong, S. Conlan, et al., “Topographical and Temporal Diversity of the Human Skin Microbiome,” Science 324 (2009): 1190.

[45] S. Kalaora, A. Nagler, D. Nejman, et al., “Identification of Bacteria-Derived HLA-Bound Peptides in Melanoma,” Nature 592 (2021): 138.

[46] C. Urbaniak, G. B. Gloor, M. Brackstone, L. Scott, M. Tangney, and G. Reid, “The Microbiota of Breast Tissue and Its Association With Breast Cancer,” Applied and Environmental Microbiology 82 (2016): 5039.

[47] A. Tzeng, N. Sangwan, M. Jia, et al., “Human Breast Microbiome Correlates With Prognostic Features and Immunological Signatures in Breast Cancer,” Genome Medicine 13 (2021): 60.

[48] L. E. Colbert, M. B. El Alam, R. Wang, et al., “Tumor-Resident Lactobacillus iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring,” Cancer Cell 41 (2023): 1945.

[49] E. Riquelme, Y. Zhang, L. Zhang, et al., “Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes,” Cell 178 (2019): 795.

[50] C. J. F. Heymann, J. M. Bard, M. F. Heymann, D. Heymann, and C. Bobin-Dubigeon, “The Intratumoral Microbiome: Characterization Methods and Functional Impact,” Cancer Letters 522 (2021): 63.

[51] C. Pleguezuelos-Manzano, J. Puschhof, A. Rosendahl Huber, A. van Hoeck, and H. M. Wood, “Mutational Signature in Colorectal Cancer Caused by Genotoxic Pks+ E. coli,” Nature 580 (2020): 269.

[52] O. D. Maddocks, K. M. Scanlon, and M. S. Donnenberg, “An Escherichia coli Effector Protein Promotes Host Mutation via Depletion of DNA Mismatch Repair Proteins,” MBio 4 (2013): e00152.

[53] J. C. Santos, M. T. Brianti, V. R. Almeida, et al., “Helicobacter pylori Infection Modulates the Expression of miRNAs Associated With DNA Mismatch Repair Pathway,” Molecular Carcinogenesis 56 (2017): 1372.

[54] J. J. Kim, H. Tao, E. Carloni, W. K. Leung, D. Y. Graham, and A. R. Sepulveda, “Helicobacter pylori Impairs DNA Mismatch Repair in Gastric Epithelial Cells,” Gastroenterology 123 (2002): 542.

[55] S. Parida, S. Wu, S. Siddharth, et al., “A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes,” Cancer discovery 11 (2021): 1138.

[56] C. E. DeStefano Shields, J. R. White, L. Chung, et al., “Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy,” Cancer discovery 11 (2021): 1792.

[57] L. Jiang, P. Wang, X. Song, et al., “Salmonella Typhimurium Reprograms Macrophage Metabolism via T3SS Effector SopE2 to Promote Intracellular Replication and Virulence,” Nature Communications 12 (2021): 879.

[58] S. Wu, Z. Ye, X. Liu, et al., “Salmonella Typhimurium Infection Increases p53 Acetylation in Intestinal Epithelial Cells,” American journal of physiology Gastrointestinal and Liver Physiology 298 (2010): G784.

[59] R. Lu, S. Wu, Y. G. Zhang, et al., “Salmonella Protein AvrA Activates the STAT3 Signaling Pathway in Colon Cancer,” Neoplasia 18 (2016): 307.

[60] W. S. Garrett, “Cancer and the Microbiota,” Science 348 (2015): 80.

[61] R. M. Thomas and C. Jobin, “Microbiota in Pancreatic Health and Disease: The Next Frontier in Microbiome Research,” Nature reviews Gastroenterology & hepatology 17 (2020): 53.

[62] T. Yu, F. Guo, Y. Yu, et al., “Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy,” Cell 170 (2017): 548.

[63] C. Kong, X. Yan, Y. Zhu, et al., “Fusobacterium nucleatum Promotes the Development of Colorectal Cancer by Activating a Cytochrome P450/Epoxyoctadecenoic Acid Axis via TLR4/Keap1/NRF2 Signaling,” Cancer Research 81 (2021): 4485.

[64] S. Chen, L. Zhang, M. Li, et al., “Fusobacterium nucleatum Reduces METTL3-Mediated m6A Modification and Contributes to Colorectal Cancer Metastasis,” Nature Communications 13 (2022): 1248.

[65] S. Guo, J. Chen, F. Chen, Q. Zeng, W. L. Liu, and G. Zhang, “Exosomes Derived From Fusobacterium nucleatum-infected Colorectal Cancer Cells Facilitate Tumour Metastasis by Selectively Carrying miR-1246/92b-3p/27a-3p and CXCL16,” Gut (2020): 321187.

[66] C. Gur, Y. Ibrahim, B. Isaacson, et al., “Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors From Immune Cell Attack,” Immunity 42 (2015): 344.

[67] S. Pushalkar, M. Hundeyin, D. Daley, et al., “The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression,” Cancer Discovery 8 (2018): 403.

[68] D. Nejman, I. Livyatan, G. Fuks, et al., “The Human Tumor Microbiome Is Composed of Tumor Type-Specific Intracellular Bacteria,” Science 368 (2020): 973.

[69] L. Seifert, G. Werba, S. Tiwari, et al., “The Necrosome Promotes Pancreatic Oncogenesis via CXCL1 and Mincle-Induced Immune Suppression,” Nature 532 (2016): 245.

[70] G. A. Vitiello, D. J. Cohen, and G. Miller, “Harnessing the Microbiome for Pancreatic Cancer Immunotherapy,” Trends in cancer 5 (2019): 670.

[71] S. Das, B. Shapiro, E. A. Vucic, S. Vogt, and D. Bar-Sagi, “Tumor Cell-Derived IL1β Promotes Desmoplasia and Immune Suppression in Pancreatic Cancer,” Cancer Research 80 (2020): 1088.

[72] C. Jin, G. K. Lagoudas, C. Zhao, et al., “Commensal Microbiota Promote Lung Cancer Development via Γδ T Cells,” Cell 176 (2019): 998.

[73] M. Uribe-Herranz, S. Rafail, S. Beghi, et al., “Gut Microbiota Modulate Dendritic Cell Antigen Presentation and Radiotherapy-Induced Antitumor Immune Response,” Journal of Clinical Investigation 130 (2020): 466.

[74] A. Fu, B. Yao, T. Dong, et al., “Tumor-Resident Intracellular Microbiota Promotes Metastatic Colonization in Breast Cancer,” Cell 185 (2022): 1356.

[75] A. Sharma, D. Kumar Arya, M. Dua, G. S. Chhatwal, and A. K. Johri, “Nano-technology for Targeted Drug Delivery to Combat Antibiotic Resistance,” Expert Opinion on Drug Delivery 9 (2012): 1325.

[76] D. G. J. Larsson and C. F. Flach, “Antibiotic Resistance in the Environment,” Nature Reviews Microbiology 20 (2022): 257.

[77] L. Dethlefsen and D. A. Relman, “Incomplete Recovery and Individualized Responses of the Human Distal Gut Microbiota to Repeated Antibiotic Perturbation,” PNAS 108, no. Suppl 1 (2011): 4554.

[78] W. Eisenreich, T. Rudel, J. Heesemann, and W. Goebel, “Link BETWEEN Antibiotic Persistence and Antibiotic Resistance in Bacterial Pathogens,” Frontiers in Cellular and Infection Microbiology 12 (2022): 900848.

[79] C. H. Chang, Y. H. Lin, C. L. Yeh, et al., “Nanoparticles Incorporated in pH-Sensitive Hydrogels as Amoxicillin Delivery for Eradication of Helicobacter pylori,” Biomacromolecules 11 (2010): 133.

[80] S. Ramteke, N. Ganesh, S. Bhattacharya, and N. K. Jain, “Amoxicillin, Clarithromycin, and Omeprazole Based Targeted Nanoparticles for the Treatment of H. pylori,” J Drug Target 17 (2009): 225.

[81] X. Lin, J. He, W. Li, et al., “Lung-Targeting Lysostaphin Microspheres for Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment and Prevention,” ACS Nano 15 (2021): 16625.

[82] C. A. Cheng, T. Deng, F. C. Lin, Y. Cai, and J. I. Zink, “Supramolecular Nanomachines as Stimuli-Responsive Gatekeepers on Mesoporous Silica Nanoparticles for Antibiotic and Cancer Drug Delivery,” Theranostics 9 (2019): 3341.

[83] L. K. Ruddaraju, S. V. N. Pammi, P. Pallela, V. S. Padavala, and V. R. M. Kolapalli, “Antibiotic Potentiation and Anti-Cancer Competence Through Bio-Mediated ZnO Nanoparticles,” Mater Sci Eng C Mater Biol Appl 103 (2019): 109756.

[84] C. Gao, X. Wang, B. Yang, et al., “Synergistic Target of Intratumoral Microbiome and Tumor by Metronidazole-Fluorouridine Nanoparticles,” ACS Nano 17 (2023): 7335.

[85] X. Kang, F. Bu, W. Feng, et al., “Dual-Cascade Responsive Nanoparticles Enhance Pancreatic Cancer Therapy by Eliminating Tumor-Resident Intracellular Bacteria,” Advanced Materials 34 (2022): e2206765.

[86] M. Godoy-Gallardo, U. Eckhard, L. M. Delgado, et al., “Antibacterial Approaches in Tissue Engineering Using Metal Ions and Nanoparticles: From Mechanisms to Applications, ” Bioact Mater 6 (2021): 4470.

[87] F. Kong, C. Fang, Y. Zhang, et al., “Abundance and Metabolism Disruptions of Intratumoral Microbiota by Chemical and Physical Actions Unfreeze Tumor Treatment Resistance,” Adv Sci (Weinh) 9 (2022): e2105523.

[88] X. Qu, F. Yin, M. Pei, et al., “Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer With Reduced Phototoxic Skin Injury,” ACS Nano 17 (2023): 11466.

[89] X. Jin, J. Zhou, G. Richey, M. Wang, S. M. C. Hong, and S. H. Hong, “Undecanoic Acid, Lauric Acid, and N-Tridecanoic Acid Inhibit Escherichia coli Persistence and Biofilm Formation,” Journal of Microbiology and Biotechnology 31 (2021): 130.

[90] D. W. Zheng, X. Dong, P. Pan, et al., “Phage-Guided Modulation of the Gut Microbiota of Mouse Models of Colorectal Cancer Augments Their Responses to Chemotherapy,” Nat Biomed Eng 3 (2019): 717.

[91] X. Dong, P. Pan, D. W. Zheng, P. Bao, X. Zeng, and X. Z. Zhang, “Bioinorganic Hybrid Bacteriophage for Modulation of Intestinal Microbiota to Remodel Tumor-Immune Microenvironment Against Colorectal Cancer,” Science Advances 6 (2020): eaba1590.

[92] Z. Chen, F. Han, Y. Du, H. Shi, and W. Zhou, “Hypoxic Microenvironment in Cancer: Molecular Mechanisms and Therapeutic Interventions,” Signal Transduct Target Ther 8 (2023): 70.

[93] T. Greenstein and B. B. Aldridge, “Tools to Develop Antibiotic Combinations That Target Drug Tolerance in Mycobacterium tuberculosis,” Frontiers in Cellular and Infection Microbiology 12 (2022): 1085946.

[94] F. Chen, Z. Zang, Z. Chen, et al., “Nanophotosensitizer-Engineered Salmonella Bacteria With Hypoxia Targeting and Photothermal-Assisted Mutual Bioaccumulation for Solid Tumor Therapy,” Biomaterials 214 (2019): 119226.

[95] P. Angsantikul, S. Thamphiwatana, Q. Zhang, et al. Adv Ther (Weinh) (2018): 1800016.

[96] N. Wang and J. Y. Fang, “Fusobacterium nucleatum, a Key Pathogenic Factor and Microbial Biomarker for Colorectal Cancer,” Trends in Microbiology 31 (2023): 159.

[97] G. J. Jeong, F. Khan, N. Tabassum, K. J. Cho, and Y. M. Kim, “Controlling Biofilm and Virulence Properties of Gram-Positive Bacteria by Targeting Wall Teichoic Acid and Lipoteichoic Acid,” International Journal of Antimicrobial Agents 62 (2023): 106941.

[98] W. F. Song, D. Zheng, S. M. Zeng, X. Zeng, and X. Z. Zhang, “Targeting to Tumor-Harbored Bacteria for Precision Tumor Therapy,” ACS Nano 16 (2022): 17402.

[99] J. Abed, J. E. Emgård, G. Zamir, et al., “Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc,” Cell Host & Microbe 20 (2016): 215.

[100] J. L. Galeano Niño, H. Wu, K. D. LaCourse, et al., “Effect of the Intratumoral Microbiota on Spatial and Cellular Heterogeneity in Cancer,” Nature 611 (2022): 810.

[101] L. Chen, R. Zhao, J. Shen, et al., “Antibacterial Fusobacterium nucleatum—Mimicking Nanomedicine to Selectively Eliminate Tumor-Colonized Bacteria and Enhance Immunotherapy Against Colorectal Cancer,” Advanced Materials 35 (2023): 2306281.

[102] E. M. Schuster, M. W. Epple, and K. M. Glaser, “TFEB Induces Mitochondrial Itaconate Synthesis to Suppress Bacterial Growth in Macrophages,” Nat Metab 4 (2022): 856.

[103] J. Wang, Y. Wang, W. Ren, D. Zhang, P. Ju, and K. Dou, ““Nano Killers” Activation by Permonosulfate Enables Efficient Anaerobic Microorganisms Disinfection,” Journal of Hazardous Materials 440 (2022): 129742.

[104] A. Gupta, S. Mumtaz, C. H. Li, I. Hussain, and V. M. Rotello, “Combatting Antibiotic-Resistant Bacteria Using Nanomaterials,” Chem. Soc. Rev. 48 (2019): 415.

[105] C. Li, R. Ye, J. Bouckaert, et al., “Flexible Nanoholey Patches for Antibiotic-Free Treatments of Skin Infections,” ACS Appl Mater Interfaces 9 (2017): 36665.

[106] R. Eisenhofer, J. J. Minich, C. Marotz, A. Cooper, R. Knight, and L. S. Weyrich, “Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations,” Trends in Microbiology 27 (2019): 105.

[107] G. Yu, M. H. Gail, D. Consonni, et al., “Characterizing Human Lung Tissue Microbiota and Its Relationship to Epidemiological and Clinical Features,” Genome biology 17 (2016): 163.

[108] A. Halimi, G. Gabarrini, M. J. Sobkowiak, et al., “Isolation of Pancreatic Microbiota From Cystic Precursors of Pancreatic Cancer With Intracellular Growth and DNA Damaging Properties,” Gut Microbes 13 (2021): 1983101.

[109] M. V. Esposito, B. Fosso, M. Nunziato, et al., “Microbiome Composition Indicate Dysbiosis and Lower Richness in Tumor Breast Tissues Compared to Healthy Adjacent Paired Tissue, Within the Same Women,” BMC cancer 22 (2022): 30.

[110] L. Parhi, T. Alon-Maimon, A. Sol, et al., “Breast Cancer Colonization by Fusobacterium nucleatum Accelerates Tumor Growth and Metastatic Progression,” Nature Communications 11 (2020): 3259.

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