Photoresponsive Nanocarriers for Potentiating Tuberculosis Therapy

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Infectious Diseases

Background:

• Drug-resistant tuberculosis (TB) poses a significant global health challenge.
• Current TB treatments face limitations due to prolonged duration and toxicity.
• Innovative therapeutic strategies are needed to combat complex bacterial survival mechanisms in TB.

Purpose of the Study:

• To develop photoresponsive nanocarriers coencapsulating isoniazid (INH) and rifampicin (RIF) for laser-assisted TB therapy.
• To evaluate the efficacy of these nanocarriers in reducing Mycobacterium tuberculosis burden.
• To assess the potential of this platform as an adjuvant strategy for precision TB treatment.

Main Methods:

• Synthesis and functionalization of gold nanorods (AuNRs) with PLGA-SH for photothermal activation.
• Development of polymeric nanocarriers encapsulating INH and RIF, with or without AuNRs.
• In vitro evaluation in murine and human macrophage models and in vivo assessment in preclinical TB models.

Main Results:

• Nanocarriers demonstrated high drug encapsulation efficiency (approx. 90%) and appropriate physicochemical properties.
• Photoactivated nanocarriers significantly reduced Mycobacterium tuberculosis burden in vitro without cytotoxicity.
• Laser-triggered nanocarriers markedly reduced pulmonary bacterial load in infected mice, even at low doses.

Conclusions:

• The developed photoresponsive nanocarriers show significant therapeutic efficacy dependent on photothermal activation.
• This platform supports a precision, light-assisted approach to TB treatment.
• The strategy has the potential to reduce systemic drug exposure and minimize toxicity in TB therapy.