| 摘要: | 大腸癌為世界上最常見的癌症之一，目前治療方式以手術切除腫瘤組織為主，並輔以放療和化療，然而目前的癌症治療手段並不會使癌細胞完全去除，這導致在癌症治療後還是有一定機率復發。
本研究開發了一種細菌質膜(Bacterial Plasma Membrane, BM)塗層奈米粒子，其奈米粒子中載入光敏劑靛氰綠(Indocyanine green, ICG)與喜樹鹼(Camptothecin, CPT)的全氟碳雙層奈米粒子(BM-ICPNPs)，BM-ICPNPs可以透過照射近紅外光使ICG進行光熱療法以及光動療法，同時釋放CPT進行化學治療，細菌質膜因具有豐富的病原體相關分子(PAMPs)，在進行光和化學治療後能夠有效的刺激免疫細胞成熟和招集，來達到促進免疫細胞對於死亡癌細胞的特異性抗原呈遞，從而增強免疫細胞對癌細胞的特異性免疫識別和清除。
在奈米粒子的粒徑及表面電位測量分析結果，ICPDNPs的尺寸為222.27 ± 18.84 nm，表面呈現負電荷(-17.11 ± 7.05 mV)，在經過細菌膜塗層後，尺寸變為235.37 ± 14.07 nm，表面呈現電荷變為-23.5 ± 7.00 mV，結果顯示塗層細菌膜後尺寸有增加。在近紅外光雷射的照射下，BM-ICPNPs表現出與ICG水溶液接近的熱療效果，且在光動治療的測試中顯著的產生出單態氧。
在細胞毒性試驗的結果顯示BM-ICPNPs含有高於40 µM ICG以及10 µM CPT時，會對CT26有毒殺效果。在體內試驗中證實了BM-ICPNPs有很好的抑癌效果，並且在腫瘤的組織切片免疫組織化學(immunohistochemistry, IHC)染色下，顯示其強大的免疫刺激能力，免疫標誌物CD4、CD8和CD11b都有很高的表現量。
從上述的實驗結果可以證實BM-ICPNPs作為一個複合了光治療、化學治療及免疫治療的材料，在癌症的治療上具有一定的潛力，可望其在癌症的治療上成為一種新興的治療材料。;Colorectal cancer is one of the most common types of cancer in the world. Current standard treatments primarily involve surgical resection of the tumor, often complemented by radiotherapy and chemotherapy. However, the treatment does not result in the complete eradication of the tumor cells, and the risk of recurrence after cancer treatment is high.
This study developed a bacterial plasma membrane (BM) coated nanoparticles in which Indocyanine green (ICG) Camptothecin (CPT) encapsulated perfluorocarbon double nanoparticles (BM-ICPNPs). BM-ICPNPs perform photothermal therapy (PTT) and photodynamic therapy (PDT) by irradiating ICG with a near-infrared (NIR) laser and releasing CPT for chemotherapy. The bacterial membrane is abundant in pathogen‐associated molecular patterns, which can effectively stimulate immune cell maturation and recruitment after photochemotherapy, to enhance the specificity of immune recognition and elimination of cancer cells.
Nanoparticle size and zeta potential analysis showed that ICPNPs have size of 222.27 ± 18.84 nm and negative surface charge (-17.11 ± 7.05 mV). After BM coating, the particle size increased to 235.37 ± 14.07 nm, and the zeta potential shifted to −23.5 ± 7.00 mV, confirming successful membrane coating. Under near-infrared (NIR) laser irradiation, BM-ICPNPs demonstrated photothermal performance comparable to that of Free ICG, and generated a significant amount of singlet oxygen in photodynamic tests.
In cytotoxicity assays, BM-ICPNPs exhibited potent cytotoxic effects against CT26 colon cancer cells at concentrations exceeding 40 μM ICG and 10 μM CPT. In vivo studies further confirmed the antitumor efficacy of BM-ICPNPs, with pronounced tumor growth inhibition. Immunohistochemical (IHC) staining analysis of tumor sections revealed robust immune activation, as evidenced by elevated expression of immune markers CD4, CD8, and CD11b.
These results suggest that BM-ICPNPs hold great promise as a multifunctional treatment strategy, combining phototherapy, chemotherapy, and immunotherapy to effectively combat colorectal cancer. |
