Abstract: Based on the proposed development of antibiotic nanozymes—a novel strategy integrating antibiotics with nanozyme structures to combat drug-resistant bacteria through a synergistic multi-mechanistic approach. Its core function relies on its peroxidase-like activity, catalyzing the conversion of endogenous H₂O₂ into highly toxic ·OH radicals, which disrupts bacterial redox homeostasis and thereby reverses resistance. Simultaneously, they degrade the biofilm matrix and eradicate persister cells. Furthermore, this system can induce fungal ferroptosis, inhibit efflux pumps, and suppress the H₂S-based antioxidant defense system, comprehensively enhancing bactericidal efficacy—this research thoroughly examines its ethical, legal, social, sustainability, and safety implications. We are committed to responsible innovation, emphasizing comprehensive biosafety and ecotoxicological evaluation, regulatory compliance, equitable access, public engagement, and stringent laboratory and environmental safety protocols to ensure the technology is developed and applied in a scientifically sound, ethically acceptable, and socially beneficial manner.

1. Intrinsic Biosafety via Molecular Design

Our core technology employs hemin as its catalytic core. As an endogenous substance in the human body—for instance, the core component of hemoglobin—its metabolic pathways are well-characterized and tightly regulated. Compared to non-biodegradable inorganic nanomaterials (e.g., metal oxides), hemin-based nanozymes exhibit inherent biocompatibility and predictable metabolic profiles at the molecular level, greatly mitigating the potential long-term toxicity risks linked to their persistent accumulation in vivo.

2. Proactive Pharmacokinetic and Safety Assessment

We recognize that the translational potential of a novel therapeutic agent hinges on its absorption, distribution, metabolism, and excretion (ADME) properties. Therefore, as the project advances, we are committed to conducting comprehensive pharmacokinetic studies to delineate the in vivo fate of our antibiotic nanozymes. This critical step will validate their safety profile, optimize dosing strategies, and provide essential data for future regulatory approval and clinical translation.

3. Active Risk Control in Laboratory Operations

All experiments involving bacterial cultures are performed in Biosafety Level 1 (BSL-1) laboratories, in strict compliance with standard operating procedures (SOPs). All experimental waste is subjected to regulated treatment—e.g., autoclaving—to ensure the absolute safety of personnel and the environment.

1. Explicit Declaration of Research Phase

We formally state that this project is currently in the early phase of foundational research, with a focus on molecular design, in vitro synthesis, and efficacy validation. No animal experiments have been carried out to date; all conclusions are drawn from results derived from cell-based assays.

2. Stringent Ethical Framework for Future Research

We acknowledge that advancing this technology to preclinical studies (note: no hyphen in "preclinical" per scientific convention) must comply with the highest ethical standards. Accordingly, we have established an ethical framework for future animal experiments, committing to full compliance with the internationally recognized "4Rs Principles" (Replacement, Reduction, Refinement and Responsibility) and ensuring all protocols obtain approval from the relevant Institutional Animal Care and Use Committee (IACUC).

3. Advancing Open Science and Knowledge Sharing

We recognize that collaboration is critical to addressing antimicrobial resistance (AMR). Thus, where feasible and without compromising core intellectual property, we plan to share the project's computational methodologies and virtual screening workflows through open-source platforms. This will support the global research community in accelerating the development of high-performance nanozymes and collectively tackling this global health challenge.

1. Addressing Global Health Disparities

Antimicrobial resistance (AMR) disproportionately impacts low- and middle-income regions (LMICs). From the technology’s design phase onward, we have integrated considerations for future equitable access. We are actively exploring opportunities to collaborate with international entities—such as the Medicines Patent Pool (MPP)—and evaluating strategies like tiered pricing models. Our goal is to ensure that this technology can potentially benefit all patients in the future, irrespective of their economic status or geographic location.

2. Targeted Public Engagement and Science Communication

To enhance societal understanding and acceptance of nanotechnology, we proactively conduct responsible knowledge dissemination:

Developed engaging educational animations that illustrate how "nanozymes" act as a "Trojan horse" to penetrate bacterial defenses.

Conducted online surveys to assess public awareness of and concerns about nanotechnology and antibiotic use. This feedback has been integrated into our communication strategy to ensure both effectiveness and transparency.

1. Strict Adherence to Biosafety Regulations

All our research activities are conducted in accordance with the legal provisions of the Biosecurity Law of the People's Republic of China. We have implemented strict management protocols for the use, storage, and disposal of biological materials.

2. Developing a Multi-Dimensional Intellectual Property Strategy

We are seeking patent protection for the core technology platform of "antibiotic-hemin co-assembly." Additionally, we plan to file method patents for the high-performance nanozyme combinations identified via our computational virtual screening—an innovative step that will help build a robust "patent moat." For the educational and outreach materials developed under this project, we have applied Creative Commons (CC) licenses to facilitate their widespread dissemination and utilization.

We recognize that the value of innovative technology lies not only in scientific breakthrough but also in its overall contribution to society. This research will establish a comprehensive ELSI governance framework, embedding ethical, legal, social, sustainability, and safety considerations into the entire R&D process. This ensures the responsible development of antibiotic nanozyme technology, ultimately contributing positively to global public health efforts. We will engage in ongoing dialogue with various stakeholders to continuously refine ELSI management strategies, fostering harmonious progress between technological innovation and social development.