人類微小病毒 B19 病毒樣顆粒的組裝及其潛在應用

人類微小病毒B19（B19V）為無套膜、單股線性DNA病毒，病毒大小介於18-26 nm，主要經飛沫傳染感染骨髓巨核細胞/紅血球前驅細胞（Megakaryocyte/erythroid progenitor cells, MEPs）。B19V病毒顆粒為正二十面體，由VP1及VP2兩種結構蛋白組成病毒殼體，其中VP2佔約為95%。過往研究發現B19V殼體蛋白可經由原核表達系統產生自行組裝之病毒樣顆粒空殼體（Virus-like Particle, VLP），其抗原性和免疫性都與B19V天然病毒顆粒相似。由於B19V VLP不具感染性，因此許多研究將其作為攜帶病原菌抗原片段（epitope）之載體應用。而本論文則是希望利用B19V VLP開發作為藥物攜帶者之可行性，透過於VLP組裝過程之中加入化療藥物Doxorubicin (DOX)進行乘載，並進行細胞存活性試驗及活體動物腫瘤抑制實驗和VLP載體趨向性試驗。研究結果顯示B19V VLP具有明顯抑制CT26小鼠結腸癌細胞生長之能力。在透過尾靜脈注射進入小鼠體內後，VLP與承載藥物之VLP-DOX兩者對腫瘤生長都具有顯著抑制效果。期望這項新發現在未來可以應用於癌症治療。

Human parvovirus B19 (B19V) is a small, non-enveloped, single-strand linear DNA virus primarily transmitted through droplets. It targets Megakaryocyte and erythroid progenitor cells. Its icosahedral virions measure between 18-26 nm and consist of two different structural proteins, VP1 (5%) and VP2 (95%). Previous studies have demonstrated that these proteins can be expressed using a prokaryotic expression system to generate recombinant proteins that spontaneously assemble into virus-like particles (VLPs) under favorable conditions. These VLPs exhibit similar antigenicity to the natural B19V virus and do not contain genetic material, making them infection-safe. Various research studies have explored their potential as an antigen carrier by linking epitopes of different pathogens with varying degrees of success. However, extensive exploration of their potential as a nanoparticle drug carrier has been lacking. Therefore, this study aims to develop a B19V VLP drug delivery system and evaluate the impact of these particles on CT26 tumor cells. It was determined that B19V VLPs can carry Doxorubicin (DOX) by incorporating it during the VLP assembly process. MTT assays revealed that both B19V VLPs and VLP-DOX exhibited an anti-tumor effect in vitro and significantly inhibited tumor growth in vivo. This novel finding holds promise for potential applications in cancer treatment.