Infectious lung diseases — including pneumonia, tuberculosis (TB), COVID-19, influenza, and emergent fungal infections — remain leading causes of morbidity and mortality worldwide. Conventional diagnostics and therapeutics have important limitations, notably diagnostic delays, rising antimicrobial resistance, and non-targeted treatments that reduce effectiveness and may increase harms. Theranostics, the combined use of diagnostics and therapeutics within an integrated precision medicine paradigm, is proposed as a transformative approach for pulmonary infections.
This review synthesizes how current advances in biotechnology and nanotechnology can be combined to develop theranostic strategies tailored to infectious lung disease, highlighting specific molecular tools, nanoplatforms for delivery and imaging, disease-focused applications, translational barriers, and priorities for future development.
Biotechnological approaches enable high-specificity detection of pathogens and direct molecular intervention. The review highlights three classes of tools:
CRISPR-Cas systems: leveraged for sequence-specific pathogen detection and potential gene-targeting interventions. These systems can form the basis of rapid molecular diagnostics with high specificity for bacterial, viral, or fungal targets.
Non-coding RNAs (ncRNAs): used both as diagnostic biomarkers and as therapeutic modulators of host or pathogen gene expression. ncRNAs can inform disease state and may be incorporated into targeted therapeutic strategies.
Monoclonal antibodies (mAbs): employed for pathogen neutralization, immune modulation, and as targeting ligands when conjugated to delivery systems. mAbs provide specificity for particular antigens and can be used diagnostically or therapeutically within theranostic constructs.
Each of these biotechnological modalities can be paired with delivery and sensing platforms to create integrated theranostic units focused on pulmonary pathogens.
Nanotechnology provides the vehicles and sensors necessary to translate molecular specificity into actionable clinical tools. The review discusses several nanoplatforms:
Nanosensors and surface-enhanced Raman spectroscopy (SERS) for sensitive, rapid detection and molecular fingerprinting of pathogens or host biomarkers.
Lipid nanoparticles and liposomes, offering biocompatible carriers for drug, gene, or vaccine cargo with potential for pulmonary delivery and controlled release.
Polymeric nanoparticles, which enable tunable degradation, payload release profiles, and surface modification for targeting.
Metallic nanoparticles and mesoporous silica nanoparticles, used for combined imaging, delivery, and sometimes intrinsic antimicrobial effects.
Biomimetic systems, which replicate cellular or vesicular properties to improve targeting, biocompatibility, and immune evasion.
Collectively, these nanocarriers can support targeted payload delivery (drugs, nucleic acids, vaccines), enable imaging and tracking, and be engineered for stimuli-responsive or controlled-release behavior to optimize therapeutic windows in the lung.
The review integrates case studies across major pulmonary conditions to illustrate applied theranostics. Examples include:
COVID-19 and influenza: rapid molecular detection paired with nanoparticle-mediated vaccine or antiviral delivery to improve timeliness of therapy and to couple diagnostics with real-time therapeutic decisions.
Tuberculosis (TB): targeted delivery systems and molecular diagnostics aim to overcome slow culture-based diagnosis and to improve drug delivery to difficult-to-reach lesions within the lung.
Pneumonia and COPD-related infections: nanosensors and targeted therapeutics could differentiate etiologies and deliver localized therapy, potentially reducing systemic toxicity.
Idiopathic pulmonary fibrosis (IPF) with infectious complications: theranostic strategies can help detect and manage infection-driven exacerbations while monitoring treatment response through integrated imaging.
These disease-focused applications demonstrate the potential of combined biotechnology and nanotechnology approaches to improve specificity, reduce diagnostic-to-treatment latency, and personalize therapy.
Despite promising preclinical advances, multiple barriers impede clinical translation. Safety concerns include toxicity and long-term effects of nanomaterials in the lung. Manufacturing and scale-up of complex nanobiologic combination products pose technical and quality-control challenges. Regulatory frameworks are often unclear for integrated theranostic devices and combination products, complicating approval pathways. Finally, economic feasibility and the need for health economic analyses to demonstrate cost-effectiveness are highlighted as essential to adoption.
The review emphasizes that these hurdles must be addressed through standardized approaches and evidence demonstrating safety, efficacy, and value.
Key priorities for future research and development described in the review include:
Designing smart, multi-stimuli-responsive nanoplatforms that react to local biochemical or physical cues for controlled drug release and adaptive imaging.
Integrating artificial intelligence (AI) for predictive modeling, pattern recognition in diagnostics, and optimization of individualized treatment regimens.
Developing closed-loop theranostic systems that couple real-time diagnostics with automated or adaptive therapeutic responses, enabling immediate adjustments based on monitored biomarkers or imaging signals.
These innovations aim to tighten the feedback loop between detection and therapy, improving personalization and outcomes in pulmonary infections.
The authors identify practical steps needed to move theranostic concepts toward clinical use: establishment of standardized preclinical models to generate robust translational data; crafting clear regulatory pathways for combination products that merge diagnostics and therapeutics; and conducting health economic studies to quantify cost-effectiveness and inform reimbursement decisions.
Realizing the promise of theranostics for infectious lung diseases will require sustained interdisciplinary collaboration among material scientists, molecular biologists, clinicians, and regulatory experts to ensure safe, effective, and economically viable solutions reach patients.