PMID- 34729311
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 11
IP  - 10
DP  - 2021 Oct
TI  - Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery 
      against complex fungal infections.
PG  - 3220-3230
LID - 10.1016/j.apsb.2021.04.020 [doi]
AB  - As a typical human pathogenic fungus, Cryptococcus neoformans is a 
      life-threatening invasive fungal pathogen with a worldwide distribution causing 
       approximately 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.
CI  - (c) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Cheng, Liting
AU  - Cheng L
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Niu, Miao-Miao
AU  - Niu MM
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of 
      Education), China Pharmaceutical University, Nanjing 210009, China.
FAU - Yan, Tong
AU  - Yan T
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Ma, Zhongyi
AU  - Ma Z
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Huang, Kexin
AU  - Huang K
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Yang, Ling
AU  - Yang L
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Zhong, Xin
AU  - Zhong X
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
FAU - Li, Chong
AU  - Li C
AD  - Medical Research Institute, College of Pharmaceutical Sciences, Southwest 
      University, Chongqing 400715, China.
LA  - eng
PT  - Journal Article
DEP - 20210508
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC8546853
OTO - NOTNLM
OT  - Albumin
OT  - AmB, amphotericin B
OT  - BBB, blood‒brain barrier
OT  - BSA, bovine serum albumin
OT  - Complex fungal infection
OT  - DDS, drug delivery system
OT  - IME, infectious microenvironment
OT  - MMP-3
OT  - MMP-3, matrix metalloproteinase 3
OT  - MTN, micro-to-nano
OT  - Microenvironment responsive
OT  - NP, nanoparticle
OT  - PEG, polyethylene glycol
OT  - PMVECs, pulmonary microvascular endothelial cells
OT  - RFP, red fluorescent protein
OT  - SPARC
OT  - SPARC, secreted protein acidic and rich in cysteine
OT  - Size-tunable strategy
COIS- The authors have no conflicts of interest to declare.
EDAT- 2021/11/04 06:00
MHDA- 2021/11/04 06:01
PMCR- 2021/05/08
CRDT- 2021/11/03 06:58
PHST- 2021/01/18 00:00 [received]
PHST- 2021/03/09 00:00 [revised]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/11/03 06:58 [entrez]
PHST- 2021/11/04 06:00 [pubmed]
PHST- 2021/11/04 06:01 [medline]
PHST- 2021/05/08 00:00 [pmc-release]
AID - S2211-3835(21)00160-X [pii]
AID - 10.1016/j.apsb.2021.04.020 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2021 Oct;11(10):3220-3230. doi: 10.1016/j.apsb.2021.04.020. 
      Epub 2021 May 8.