製備搭載5-氟尿嘧啶之微小病毒B19病毒樣顆粒在腸癌治療之研究

人類微小病毒 B19 (B19V)屬於微小病毒科(Parvoviridae)，單股的 DNA 病毒，無外套模且型態為正二十面體，大小約為 20-24 nm。主要由 VP1、VP2 兩種結構蛋白組成病毒殼體，其中 VP1 佔約 5%，VP2 佔約 95%。過往研究發現 B19V-VP2 殼體蛋白可經由原核表達系統產生可自行組裝之類病毒顆粒空殼體（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，因此許多研究進行作為攜帶病原菌抗原片段（epitope）或將其修飾後作為載體之應用。化療藥物具有療效，可以有效抑制和殺死癌細胞，但同時也可能伴隨副作用的產生。因此本論文將進行B19V VLP作為藥物載體之可行性。我們使用5-氟尿嘧啶(5-Fu)化療藥物進行相關實驗。研究結果顯示B19V VLP能有效搭載5-Fu藥物(VLP-5-Fu)，並有效抑制小鼠腸癌CT26腫瘤細胞生長及腫瘤異種移植小鼠的腫瘤生長。其中VLP-5-Fu還能減緩5-Fu藥物所造成的腹瀉情形。綜合以上結果，搭載5-FU藥物的VLP不僅可避免藥物引起的腹瀉副作用，還能有效抑制小鼠腫瘤的生長。

Human parvovirus B19 (B19V) is a small, non-enveloped virus with a single-stranded DNA genome and an icosahedral capsid structure approximately 20–24 nm in diameter. The capsid primarily comprises two structural proteins, VP2 (95%) and VP1 (5%). When expressed in prokaryotic systems, the VP2 protein can self-assemble into virus-like particles (VLPs) that exhibit similar antigenicity and immunogenicity to native B19V, while remaining non-infectious. Owing to these properties, B19V VLPs have been widely studied as platforms for presenting antigenic epitopes or delivering therapeutic agents. In this study, we evaluated the potential of B19V VLPs as drug delivery vehicles for the chemotherapeutic agent 5-fluorouracil (5-Fu). VLPs were successfully loaded with 5-Fu (VLP-5-Fu), and in vitro experiments demonstrated significant inhibition of murine colon cancer CT26 cell proliferation. In an animal xenograft model, VLP-5-Fu suppressed tumor growth and alleviated 5-Fu-induced diarrhea. These results suggest that B19V VLPs can serve as effective nanocarriers for chemotherapeutic drugs, offering targeted delivery to tumor sites while reducing systemic side effects, and may represent a promising strategy for improving the efficacy and safety of cancer treatment.