Transient embolization with microspheres of polyhydroxyalkanoate renders efficient adenoviral transduction of pancreatic capillary in vivo.
BACKGROUND
Our previous study showed an efficient targeting of islets of Langerhans by adenoviral injection via the celiac trunk. Unexpectedly, none of the endothelial cells was infected given the direct contact between adenoviruses and the capillary wall. The present study intended to provide an efficient approach for adenoviral targeting of the microcapillary endothelial cells in the pancreas.


METHODS
We prepared microspheres of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with a size comparable to the diameter of capillary (5-10 µm). Scanning electron microscopy was applied to verify that adenoviruses carrying a green fluorescence protein gene were complexed with PHBHHx-microspheres after 30 min of co-incubation. The complexes were then injected into the pancreas of mice via the celiac trunk.


RESULTS
Approximately 40% of endothelial cells in the pancreas were labeled 5 days after surgery. Islet cells were labeled occasionally, whereas labeling of the acinar and ductal tissues was barely detectable. Endothelium targeting was inefficient in other internal organs. Consistent with the reported superior tissue compatibility of PHBHHx, no discernable microspheres were found in all of the organs examined. Furthermore, splenocyte activation was dampened when adenoviruses were complexed with the microspheres.


CONCLUSIONS
The present study has established an approach for efficient pancreatic capillary targeting by using microsphere-adenoviral complexes. This procedure could be invaluable for the treatment of capillary-related diseases.
Multidisciplinary Research Center, Shantou University, Shantou, Guangdong, China.
Shui-Li
SL
Zhang
De-Jin
DJ
Zheng
Wen-Zhu
WZ
Fan
Dai-Xu
DX
Wei
Si-Wu
SW
Peng
Mi-Mi
MM
Tang
Guo-Qiang
GQ
Chen
Chi-Ju
CJ
Wei
D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D000818:Animals; D002318:Cardiovascular Diseases / Q000628:therapy; D004621:Embolization, Therapeutic; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism / Q000821:virology; D008099:Liver / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D055806:Microvessels / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D010316:Particle Size; D054813:Polyhydroxyalkanoates / Q000138:chemical synthesis / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000821:virology; D014161:Transduction, Genetic
D054813:Polyhydroxyalkanoates; D012235:Rhodamines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins