研究利用新型微脂體 (LPPC) 包覆藥物及吸附導向分子以治療犬乳癌

Abstract

研究利用新型微脂體 (LPPC) 包覆藥物及吸附導向分子以治療犬乳癌 藥物之包覆，在生物治療及應用上具其極重要的地位，而今之研究多趨向配合導向分子，將可使藥物更有效率的到達該導向分子標定之目標組織或細胞。本實驗室將開發一種新型微脂體 (LPPC)，而初步實驗結果顯示其具有以下特點：(1) 具有奈米化之大小，(2) 此微脂體可用以包覆藥物，(3) 此微脂體可有效且穩定吸附蛋白質或胜肽類分子，且由初步實驗結果可知，先行結合在微脂體上之蛋白質，不為後加入之蛋白質所取代，亦說明其不會被競爭取代之特殊性質，此性質為第一次被發明及發現，(4) 此微脂體具可離心之特性。然而此新型微脂體 (LPPC) 性質未盡清楚亦尚未最佳化，故本計畫將研究，(1) 發展最佳化之新型微脂體 (LPPC) 並觀測其特性，(2) 測試微脂體 (LPPC) 與導向分子之結合能力及其導向之效果，(3) 微脂體 (LPPC) 包覆藥物之效率，(4) 利用此之系統治療犬類乳腺腫瘤 (MGT)。而RGD-4C序列能與腫瘤細胞上的integrin αvβ3專一性的結合，故本研究中將利用RGD-4C作為導向分子，利用具此導向分子之微脂體 (LPPC) 將藥物運送至犬類乳癌細胞，以達到治療之目的。

Study of a Novel Liposome (LPPC) for Encapsulating Drug and Adsorbing Target Peptides to Treat Canine Mammary Gland Tumor The research of drug- delivery system is an important topic on treatment of diseases. Using targeting molecules to improve drug delivery efficiency is a tendency in recent studies. In this research, we are going to develop a novel liposome called Lipo-PEI-PEG complex (LPPC), and the preliminary results have shown four properties of LPPC: (1) LPPC is a nano-particle, (2) LPPC has ability for drug encapsulation, (3) LPPC can adsorb proteins or peptides effectively and stably. Moreover, we also demonstrated that the protein adsorbed at first time by LPPC cannot be competed by other proteins added later. This special property is the first time to be developed . And, (4) LPPC can be precipitated by centrifugation. However, the complete properties of LPPC are still unclear and the development of LPPC system is not optimized, either. Therefore, the purposes of this project are to: (1) optimize the procedure of LPPC and investigate its’ properties, (2) to measure the binding affinity between the LPPC and targeting molecule, and the targeting efficiency of LPPC with targeting molecule, (3) to measure the quantity of drug encapsulated by LPPC, and (4) to utilize this system to treat canine mammary gland tumor (MGT). RGD-4C, a peptide bound with integrin αvβ3 on tumor surface, will later be applied to this study as a targeting molecule. This drug-delivery system composed of RGD-4D-adsorbed LPPC will be employed as a novel cancer therapy to treat canine mammary gland tumor (MGT).