Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections
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 o...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221138352100160X |
| _version_ | 1818930111537217536 |
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| author | Liting Cheng Miao-Miao Niu Tong Yan Zhongyi Ma Kexin Huang Ling Yang Xin Zhong Chong Li |
| author_facet | Liting Cheng Miao-Miao Niu Tong Yan Zhongyi Ma Kexin Huang Ling Yang Xin Zhong Chong Li |
| author_sort | Liting Cheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T03:55:30Z |
| format | Article |
| id | doaj.art-dc5ad4171fa64c95b44055ca28eeb756 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-20T03:55:30Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-dc5ad4171fa64c95b44055ca28eeb7562022-12-21T19:54:19ZengElsevierActa Pharmaceutica Sinica B2211-38352021-10-01111032203230Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infectionsLiting Cheng0Miao-Miao Niu1Tong Yan2Zhongyi Ma3Kexin Huang4Ling Yang5Xin Zhong6Chong Li7Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaMedical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S221138352100160XAlbuminSPARCMMP-3Size-tunable strategyMicroenvironment responsiveComplex fungal infection |
| spellingShingle | Liting Cheng Miao-Miao Niu Tong Yan Zhongyi Ma Kexin Huang Ling Yang Xin Zhong Chong Li Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections Acta Pharmaceutica Sinica B Albumin SPARC MMP-3 Size-tunable strategy Microenvironment responsive Complex fungal infection |
| title | Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections |
| title_full | Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections |
| title_fullStr | Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections |
| title_full_unstemmed | Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections |
| title_short | Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections |
| title_sort | bioresponsive micro to nano albumin based systems for targeted drug delivery against complex fungal infections |
| topic | Albumin SPARC MMP-3 Size-tunable strategy Microenvironment responsive Complex fungal infection |
| url | http://www.sciencedirect.com/science/article/pii/S221138352100160X |
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