دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections.
المؤلفون: Cheng L; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Niu MM; Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China., Yan T; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Ma Z; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Huang K; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Yang L; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Zhong X; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China., Li C; Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
المصدر: Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2021 Oct; Vol. 11 (10), pp. 3220-3230. Date of Electronic Publication: 2021 May 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101600560 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2211-3835 (Print) Linking ISSN: 22113835 NLM ISO Abbreviation: Acta Pharm Sin B Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier, 2011-
مستخلص: 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.
Competing Interests: The authors have no conflicts of interest to declare.
(© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)
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فهرسة مساهمة: Keywords: Albumin; AmB, amphotericin B; BBB, blood‒brain barrier; BSA, bovine serum albumin; Complex fungal infection; DDS, drug delivery system; IME, infectious microenvironment; MMP-3; MMP-3, matrix metalloproteinase 3; MTN, micro-to-nano; Microenvironment responsive; NP, nanoparticle; PEG, polyethylene glycol; PMVECs, pulmonary microvascular endothelial cells; RFP, red fluorescent protein; SPARC; SPARC, secreted protein acidic and rich in cysteine; Size-tunable strategy
تواريخ الأحداث: Date Created: 20211103 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC8546853
DOI: 10.1016/j.apsb.2021.04.020
PMID: 34729311
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-3835
DOI:10.1016/j.apsb.2021.04.020