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Liver Cancer Targeting of Doxorubicin with Reduced Distribution to the Heart Using Hematoporphyrin-Modified Albumin Nanoparticles in Rats
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- Authors
- Advisor
- 심창구
- Major
- 제약학과
- Issue Date
- 2012-02
- Publisher
- 서울대학교 대학원
- Abstract
- Purpose: To evaluate the usefulness of hematoporphyrin (HP)-modification of the surface of doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanoparticles(NPs) in the liver cancer-selective delivery of DOX.
Methods: HP-modified NPs (HP-NPs) were prepared by conjugation of amino groups on the surface of NPs with HP, a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells. In vitro cellular accumulation of DOX, in vivo biodistribution of DOX, safety, and anti-tumor efficacy were evaluated for HP-NPs.
Results: Cytotoxicity and accumulation of DOX were in the order of HP-NPs >NPs >solution form (SOL). Cellular uptake from HP-NPs was proportional to the expression level of LDL receptors on the cells, indicating possible involvement of LDL receptor-mediated endocytosis (RME) in uptake. The merit index, an AUC ratio of DOX in liver (target organ) to DOX in heart (major side effect organ) following iv administration of HP-NPs to hepatoma rats, was 132.5 and 4 times greater compared to SOL and NPs, respectively. The greatest suppression of body weight decrease and tumor size increase was observed for iv administered HP-NPs in tumor-bearing mice.
Conclusions: HP modification appears to be useful in selective delivery of NP-loaded DOX to tumors.
- Language
- eng
- URI
- https://hdl.handle.net/10371/156649
http://dcollection.snu.ac.kr:80/jsp/common/DcLoOrgPer.jsp?sItemId=000000002070
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