Research output: Contribution to journal › Article › Academic › peer-review
Photochemical internalization enhances cytosolic release of antibiotic and increases its efficacy against staphylococcal infection. / Zhang, Xiaolin; de Boer, Leonie; Heiliegers, Laura et al.
In: Journal of controlled release, Vol. 283, 2018, p. 214-222.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Photochemical internalization enhances cytosolic release of antibiotic and increases its efficacy against staphylococcal infection
AU - Zhang, Xiaolin
AU - de Boer, Leonie
AU - Heiliegers, Laura
AU - Man-Bovenkerk, Sandra
AU - Selbo, P. l Kristian
AU - Drijfhout, Jan W.
AU - Høgset, Anders
AU - Zaat, Sebastian A. J.
PY - 2018
Y1 - 2018
N2 - Bacterial pathogens such as Staphylococcus aureus and Staphylococcus epidermidis can survive in different types of cells including professional phagocytes, causing intracellular infections. Antibiotic treatment of intracellular infections is often unsuccessful due to the low efficacy of most antibiotics inside cells. Therefore, novel techniques which can improve intracellular activity of antibiotics are urgently needed. We aimed to use photochemical internalization (PCI) to enhance cytosolic release of antibiotics from endocytic vesicles after internalization. Our results show that PCI indeed caused cytosolic release of gentamicin and significantly increased its efficacy against S. epidermidis in vitro in mouse macrophages. Upon illumination for 15 min, the killing of intracellular S. epidermidis in RAW 264.7 cells by 10 or 30 μg/ml gentamicin was increased to 1 or 3 CFU log, respectively, owing to the use of PCI, whereas no killing by gentamicin only without PCI was observed. Moreover, survival of S. aureus-infected zebrafish embryos was significantly improved by treatment with PCI-gentamicin. PCI improved the therapeutic efficacy of gentamicin at a dose of 0.1 ng per embryo to a level similar to that of a dose of 0.4 ng per embryo, indicating that PCI can lower the antibiotic dose required for treating (intracellular) staphylococcal infection. Thus, the present study shows that PCI is a promising novel approach to enhance the intracellular efficacy of antibiotics via cytosolic release, allowing them to reach intracellular bacteria. This will expand their therapeutic window and will increase the numbers of antibiotics which can be used for treatment of intracellular infections.
AB - Bacterial pathogens such as Staphylococcus aureus and Staphylococcus epidermidis can survive in different types of cells including professional phagocytes, causing intracellular infections. Antibiotic treatment of intracellular infections is often unsuccessful due to the low efficacy of most antibiotics inside cells. Therefore, novel techniques which can improve intracellular activity of antibiotics are urgently needed. We aimed to use photochemical internalization (PCI) to enhance cytosolic release of antibiotics from endocytic vesicles after internalization. Our results show that PCI indeed caused cytosolic release of gentamicin and significantly increased its efficacy against S. epidermidis in vitro in mouse macrophages. Upon illumination for 15 min, the killing of intracellular S. epidermidis in RAW 264.7 cells by 10 or 30 μg/ml gentamicin was increased to 1 or 3 CFU log, respectively, owing to the use of PCI, whereas no killing by gentamicin only without PCI was observed. Moreover, survival of S. aureus-infected zebrafish embryos was significantly improved by treatment with PCI-gentamicin. PCI improved the therapeutic efficacy of gentamicin at a dose of 0.1 ng per embryo to a level similar to that of a dose of 0.4 ng per embryo, indicating that PCI can lower the antibiotic dose required for treating (intracellular) staphylococcal infection. Thus, the present study shows that PCI is a promising novel approach to enhance the intracellular efficacy of antibiotics via cytosolic release, allowing them to reach intracellular bacteria. This will expand their therapeutic window and will increase the numbers of antibiotics which can be used for treatment of intracellular infections.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85048573012&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29883696
U2 - 10.1016/j.jconrel.2018.06.004
DO - 10.1016/j.jconrel.2018.06.004
M3 - Article
C2 - 29883696
VL - 283
SP - 214
EP - 222
JO - Journal of controlled release
JF - Journal of controlled release
SN - 0168-3659
ER -
ID: 5528007