Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections

Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections
The bioresponsive micro-to-nano albumin-based system was accumulated in the lungs and responds to the upregulated MMP-3, then targeted the lung tissue, brain, and infected macrophages, reaching multiple targets and efficient treatment. Credit: Acta Pharmaceutica Sinica B

As a typical human pathogenic fungus, Cryptococcus neoformansis a life-threatening invasive fungal pathogen with a worldwide distribution causing ∼700,000 deaths annually. Cryptococcosis is not just an infection with multi-organ involvement, intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C. neoformansinfections. Because adequate accumulation of drugs at target organs and cells is still difficult to achieve, an effective delivery strategy is desperately required to treat these infections.

In this article the authors report a bioresponsive micro-to-nano (MTN) system that effectively clears the C. neoformans in vivo. This strategy is based on the authors in-depth study of the overexpression of matrix metalloproteinase 3 (MMP-3) in infectious microenvironments (IMEs) and secreted protein acidic and rich in cysteine (SPARC) in several associated . In this MTN system, (BSA, a natural ligand of SPARC) was used for the preparation of nanoparticles (NPs), and then microspheres were constructed by conjugation with a special linker, which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide. This MTN system was mechanically captured by the smallest capillaries of the lungs after , and then hydrolyzed into BSA NPs by MMP-3 in the IMEs. The NPs further targeted the , brain and infected macrophages based on the overexpression of SPARC, reaching multiple targets and achieving efficient treatment.

The authors have developed a size-tunable strategy where microspheres "shrink" to NPs in IMEs, which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.


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More information: Liting Cheng et al, Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections, Acta Pharmaceutica Sinica B (2021). DOI: 10.1016/j.apsb.2021.04.020
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Citation: Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections (2021, August 18) retrieved 23 October 2021 from https://phys.org/news/2021-08-bioresponsive-micro-to-nano-albumin-based-drug-delivery.html
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