雙重免疫遮蔽性奈米載體應用於藥物傳遞及癌症造影

Dual stealth nanocarriers for drug delivery and cancer imaging

徐維新(Wei-Hsin Hsu)

指導教授 ： 羅建苗 ； 薛敬和

國立清華大學/原子科學院/生醫工程與環境科學系/碩士(2010年)

https://doi.org/10.6843/NTHU.2010.00248

摘要

In the drug delivery system utilizing nanoparticle as carrier, sizes of the particles have been shown to influent the effectiveness of the delivery. However, the effects of the particle shapes have received little attention. In this work, we investigated particles with same volume but with different shapes, namely spherical nanoparticles (SNPs) and hexagonal nanoprisms (HNPs), and observed their behaviors in vitro and in vivo. The nanoparticles were constructed with the multifunctional block copolymer component, mPEG-b-P(HEMA-co-histidine-PLA). This multifunctional copolymer was synthesized via free-radical copolymerization and through solvent exchange process that induced self-assembling to the desired structures. We have shown that the different shapes of nanoparticles could be formed by adjusting the copolymer property and the formulation parameters. From this work, it was demonstrated that the morphology of the nanoparticles played an important role in mitigating macrophage responses, and the phagocytosis by macrophage measured by flow cytometry was 91.6±0.8% of SNPs and 68.1±2.4% of HNPs at the 48h co-incubation. The functional group of copolymer, histidine, is a biodegradable and pH-sensitivity molecule, being readily protonated at intracellular pH change after cancer cell uptake. In addition, histidine is characterized as a good chelator to [99mTc(H2O)3(CO)3]+ for forming radiotracer for imaging studies. To understand the in vivo pharmacokinetics and biodistributions of these nanoparticles, these particles were labeled with 99mTc or the fluorescent moiety Cy5.5 and studied in animals. With longer circulation in the blood, the 99mTc-labeled HNPs accumulated better in the tumor site than did the SNPs with the same radiolabel. The tumor to liver uptake ratio of HNPs was two-fold higher than that of SNPs (1.176 of HNPs, 0.604 of SNPs). In the optical image, the Cy5.5-labeled HNPs were excreted mainly from the renal clearance and Cy5.5-labeled SNPs were eliminated through the hepatic metabolism. In this thesis, in vitro and in vivo studies have investigated the dual stealth characters including the pegylation and the structure of hexagonal prism for the mPEG-b-P(HEMA-co-histidine-PLA) formed nanoparticles. The dual stealth characters of the nanocarriers could be adopted in clinical application for in safe and efficient delivery for cancer therapy.

關鍵字

長效循環 ； 免疫遮蔽性 ； 六角奈米柱

並列摘要

無資料

並列關鍵字

long circulation ； stealth ； hexagonal nanoprisms

參考文獻

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