Treating Fibrosis with Nanomedicine: A Clinical Review of Anti-fibrotic Strategies for Liver and Lung Disease View PDF

Treating fibrosis with nanomedicine has emerged as a promising frontier in the management of both liver and lung diseases, with recent research emphasizing targeted delivery systems, molecular pathway modulation, and innovative therapeutic agents [1-9]. This literature review presents current findings on anti-fibrotic strategies, focusing on nanomedicine applications, as derived from the literature. One of the central themes in anti-fibrotic therapy is the development of targeted delivery systems to enhance drug efficacy and reduce systemic side effects. Sun et al. [10] introduced a hybrid system combining clodronate-loaded liposomes with fibroblast-derived exosomal systems, designed specifically for pulmonary fibrosis. This approach exemplifies how nanocarriers can improve drug delivery to fibrotic lung tissue, potentially increasing therapeutic concentrations at the site of pathology. Similarly, the use of nanomedicine in liver fibrosis is implied through the exploration of molecular targets and delivery mechanisms [11-17].

Molecular signaling pathways are pivotal in the pathogenesis of fibrosis, and targeting these pathways with nanomedicine offers a strategic advantage [18-24]. Raguraman et al. [25] highlighted the significance of pathways common to diabetes, lung diseases, and cancer, such as Wnt/β-catenin and other signaling cascades. These pathways are attractive targets for nanomedicine-based interventions, which can deliver inhibitors or modulators directly to affected cells, thereby enhancing specificity and reducing off-target effects. For instance, Li et al. [26] discussed the Wnt/β-catenin pathway’s role in renal fibrosis, suggesting that nanocarrier systems could be employed to deliver pathway-specific inhibitors, although direct nanomedicine applications are not explicitly described.

In the context of lung fibrosis, mesenchymal stromal cells have garnered attention due to their regenerative and anti-fibrotic properties [27-34]. Pelizzo et al. [35] reviewed the potential of mesenchymal stromal cells in pediatric interstitial lung disease, emphasizing their tissue-regenerative capabilities. While the review does not specify nanomedicine techniques, the combination of mesenchymal stromal cells with nanocarriers could potentiate their therapeutic effects, a concept supported by the broader trend of integrating cell therapy with nanotechnology to improve delivery and efficacy. Natural compounds and herbal formulations also feature as potential antifibrotic agents. Lao et al. [36] discussed Maimendong Decoction, which has shown anti-fibrotic effects. Although the review does not specify nanomedicine delivery systems, encapsulating such herbal extracts within nanoparticles could enhance bioavailability and targeted delivery, aligning with the overall trend of nanomedicine in fibrosis treatment.

Preclinical studies have provided compelling evidence for the efficacy of nanomedicine-based approaches. Thannickal et al. [37] examined the role of NOX1/4 inhibitors, such as setanaxib, in liver, kidney, and lung fibrosis. While the review focuses on the preclinical evidence of setanaxib, it underscores the potential of nanocarrier systems to improve the delivery and potency of such inhibitors across multiple fibrotic diseases. Similarly, Zhang et al. [38] highlighted various molecular targets, including small molecules and natural compounds, which could be delivered via nanocarriers to enhance therapeutic outcomes. In lung fibrosis, innovative nanomedicine strategies are also evident in the development of exosomal systems. Sun et al. [10] demonstrated how fibroblast-derived exosomal hybrids could serve as delivery vehicles, potentially applicable to other fibrotic conditions. Exosomes, as natural nanocarriers, offer advantages such as biocompatibility and intrinsic targeting capabilities, making them attractive for clinical translation.

Furthermore, the potential of nanomedicine extends to gene therapy approaches. Harrison [39] reviewed RNA- and DNA-based therapies for cystic fibrosis lung disease, emphasizing the importance of delivery systems. Although not explicitly focused on fibrosis, these methodologies could be adapted for delivering anti-fibrotic nucleic acids, such as small interfering RNAs (siRNAs) or antisense oligonucleotides, to fibrotic tissues, thereby modulating pathogenic gene expression. Emerging molecular targets like CCL24 and bone morphogenetic proteins are also being explored for their anti-fibrotic potential. Levy et al. [40] discussed CCL24-blocking antibodies, which could be delivered via nanocarriers to modulate immune and fibrotic pathways. Similarly, Ye et al. [41] reviewed bone morphogenetic proteins and their receptors in pulmonary fibrosis, suggesting that nanomedicine could facilitate targeted delivery of bone morphogenetic proteins mimetics or modulators to promote fibrosis resolution.

In summary, the integration of nanomedicine into anti-fibrotic strategies offers a multifaceted approach to tackling fibrosis in liver and lung diseases. The ability to enhance targeted delivery, improve bioavailability, and modulate specific molecular pathways positions nanomedicine as a transformative tool in this field. While many of these strategies are still in preclinical or early clinical stages, the evidence underscores their potential to revolutionize fibrosis treatment by enabling precise, effective, and safe therapeutic interventions.