Work

Inspiration of Nanoengineered Antimicrobial Therapeutics Against Nontuberculous Mycobacterial Infection

Year: 2026

Type: review

Abstract: Non-tuberculous mycobacteria (NTM), a diverse collection of environmentally ubiquitous pathogens, are emerging as a significant global public health concern with rising incidence and prevalence. NTM infections occur predominantly in immunocompromised populations and present as pulmonary, disseminated, and skin/soft tissue infections. Clinically prevalent NTM species are exhibiting inherent and acquired multidrug resistance, which is mediated by biofilm formation, efflux pump expression and target-site mutations, rendering conventional therapies increasingly ineffective. Current clinical management relies on prolonged, multi-drug antibiotic regimens, but are limited by poor efficacy, severe adverse effects and high rates of recurrence. This therapeutic impasse underscores an urgent need for novel intervention strategies. Engineered nanocarriers, including liposomes, polymeric, lipid-based and inorganic nanoparticles, encapsulate conventional antimicrobials to enhance bioavailability, prolong systemic circulation, improve penetration into infected tissues and biofilms, and facilitate uptake by infected macrophages for intracellular delivery. In addition, nanoplatforms can be engineered for targeted delivery, co-delivery of synergistic antimicrobials or host-directed agents, immune modulation, and stimulus-responsive release triggered by infection-related cues including acidic pH, reactive oxygen species (ROS), and enzymes. These multifunctional systems can help overcome physiological and cellular barriers while minimizing off-target toxicity. This review summarizes key clinical NTM species, their pathogenic traits, and molecular mechanisms of drug resistance. It assesses limitations of current regimens and highlights advances in nanotechnology-based antimicrobial delivery strategies, with emphasis on targeted delivery, intracellular trafficking, biofilm disruption, immunomodulation and key translational challenges. These strategies primarily target pulmonary NTM infection (the most common clinical manifestation), while this review briefly covers their applications in disseminated, cutaneous and lymph node NTM infections. The integration of nanomedicine holds the potential to revolutionize the therapeutic landscape, facilitating the development of more effective and targeted interventions against these challenging infections.

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s644904