The global rise of such MDR bacteria, particularly the intracellular pathogens, has created formidable challenges for clinical treatment. These bacteria possess the ability to invade and persist within host cells, thereby evading the bactericidal activity of conventional antibiotics, which are often limited by their poor cellular penetration and inability to reach therapeutic intracellular concentrations. As a result, these infections frequently lead to treatment failures, chronic disease, and increased selective pressure for additional resistance mechanisms. Prolonged and improper use of standard antibiotics further compounds this problem by promoting the evolution of resistant bacterial strains and diminishing the efficacy of the existing antimicrobial arsenal.

Amid these challenges, innovative strategies have emerged and focused on advanced drug delivery and novel antimicrobial agents.
Nanoparticle-based drug delivery systems, which include carriers such as hydrogels, liposomes, polymeric micelles, and inorganic nanoparticles, offer tailored properties for improved cellular uptake and controlled drug release in the infection microenvironment.

Parallel to these advances, naturally-derived antimicrobials—including plant essential oils (e.g., basil, thyme, oregano, cinnamon, clove, rosemary, and trans-cinnamaldehyde), animal-derived enzymes (lysozyme, lactoferrin), bacteriocins (nisin, natamycin), and natural polymers (chitosan)—present multiple mechanisms for combating resistance and supporting host immunity. Together, these approaches provide promising avenues for overcoming the persistent threat of antimicrobial resistance (AMR).

The primary goal of this Research Topic is to elucidate the mechanisms and therapeutic advantages of utilizing nanodrug delivery systems and natural antimicrobials to enhance intracellular antibacterial efficacy. This includes a detailed examination of how specific nanocarrier characteristics—such as size, surface charge, and targeted modifications—influence intracellular delivery and pharmacokinetics. In addition, this Research Topic seeks to evaluate the ability of nano-formulated drugs to bypass mechanisms of bacterial resistance and biofilm barriers that hinder conventional therapeutics. Emphasis will also be given to studies exploring the synergistic effects between nanotechnology-based interventions, natural antimicrobials, and the host immune response, with the overall aim of identifying strategies that improve outcomes against MDR intracellular pathogens.

We invite contributions that address, but are not limited to, the following themes:
o Design and development of novel nanocarriers for intracellular delivery of antibacterial agents, including but not limited to hydrogels, liposomes, polymeric micelles, and inorganic nanoparticles.
o Stimuli-responsive nanosystems engineered for precise and controlled release of therapeutics in response to infection-specific cues.
o Combinatorial strategies utilizing nanocarriers to co-deliver antibiotics with immunomodulatory or natural agents for synergistic effects.
o Mechanistic studies on how nanodrugs can overcome intracellular bacterial resistance and disrupt biofilms.
o In vitro and in vivo evaluations of the efficacy, safety, and pharmacodynamics of nano-antibacterial systems in the context of MDR infections.

All manuscript types are welcome, including Brief Research Reports, Editorials, Methods, Mini Reviews, Original Research, Perspectives, Reviews, and Systematic Reviews.

Are you interested in contributing a manuscript to this Research Topic?

Nanoparticles as a Potential and Impactive Role in Delivering Natural Antimicrobial Elements in Curbing Bacterial Resistance