Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections
| Autor: | Zhongyi Ma, Miao-Miao Niu, Tong Yan, Liting Cheng, Kexin Huang, Xin Zhong, Ling Yang, Chong Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microenvironment responsive
SPARC secreted protein acidic and rich in cysteine Peptide RM1-950 Microbiology RFP red fluorescent protein 03 medical and health sciences IME infectious microenvironment 0302 clinical medicine BBB blood‒brain barrier NP nanoparticle Extracellular medicine Distribution (pharmacology) MTN micro-to-nano General Pharmacology Toxicology and Pharmaceutics Bovine serum albumin AmB amphotericin B PEG polyethylene glycol 030304 developmental biology chemistry.chemical_classification Cryptococcus neoformans 0303 health sciences MMP-3 PMVECs pulmonary microvascular endothelial cells biology Complex fungal infection Albumin MMP-3 matrix metalloproteinase 3 DDS drug delivery system SPARC biology.organism_classification medicine.disease Size-tunable strategy chemistry Targeted drug delivery 030220 oncology & carcinogenesis Cryptococcosis biology.protein Original Article BSA bovine serum albumin Therapeutics. Pharmacology Intracellular |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 11, Iss 10, Pp 3220-3230 (2021) Acta Pharmaceutica Sinica. B |
| ISSN: | 2211-3835 |
| Popis: | As a typical human pathogenic fungus, Cryptococcus neoformans is 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. neoformans infections. 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. Here, we report a bioresponsive micro-to-nano (MTN) system that effectively clears the C. neoformans in vivo. This strategy is based on our 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 target cells. In this MTN system, bovine serum albumin (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 intravenous injection, and then hydrolyzed into BSA NPs by MMP-3 in the IMEs. The NPs further targeted the lung tissue, brain and infected macrophages based on the overexpression of SPARC, reaching multiple targets and achieving efficient treatment. We 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. Graphical abstract 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.Image 1 |
| Databáze: | OpenAIRE |
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