HPMA-LMA Copolymer Drug Carriers in Oncology: An in Vivo PET Study to Assess the Tumor Line-Specific Polymer Uptake and Body Distribution
详细信息 查看全文
- 作者：Mareli Allmeroth ; Dorothea Moderegger ; Daniel G眉ndel ; Kaloian Koynov ; Hans-Georg Buchholz ; Kristin Mohr ; Frank R枚sch ; Rudolf Zentel ; Oliver Thews
- 刊名：Biomacromolecules
- 出版年：2013
- 出版时间：September 9, 2013
- 年：2013
- 卷：14
- 期：9
- 页码：3091-3101
- 全文大小：542K
- 年卷期：v.14,no.9(September 9, 2013)
- ISSN：1526-4602
文摘
Polymeric drug carriers aim to selectively target tumors in combination with protecting normal tissue. In this regard polymer structure and molecular weight are key factors considering organ distribution and tumor accumulation of the polymeric drug delivery system. Four different HPMA based copolymer structures (random as well as block copolymers with lauryl methacrylate as hydrophobic block) varying in molecular weight, size and resulting architecture were analyzed in two different tumor models (AT1 prostate carcinoma and Walker-256 mammary carcinoma) in vivo. Polymers were labeled with 18F and organ/tumor uptake was followed by 渭PET imaging and ex vivo biodistribution. Vascular permeability was measured by dextran extravasation and vascular density by immunohistochemistry. Cellular polymer uptake was determined in vitro using fluorescence-labeled polymers. Most strikingly, the high molecular weight HPMA-LMA random copolymer demonstrated highest tumor uptake and blood pool concentration. The molecular structure (e.g., amphiphilicity) is holding a higher impact on desired in vivo properties than polymer size. The results also revealed pronounced differences between the tumor models although vascular permeability was almost comparable. Accumulation in Walker-256 carcinomas was much higher, presumably due to a better cellular uptake in this cell line and a denser vascular network in the tumors. These investigations clearly indicate that the properties of the individual tumor determine the suitability of polymeric drug carriers. The findings also illustrate the general necessity of a preclinical screening to analyze polymer uptake for each individual patient (e.g., by noninvasive PET imaging) in order to individualize polymer-based chemotherapy.