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磁性奈米顆粒擔載刺蝟路徑抑制藥物對肝癌細胞的熱療與標靶研究

為了解決Caac report的問題，作者柯利雅 這樣論述：

磁性奈米粒子在生物技術中由於擁有很多具有潛力的應用而備受關注，並且已經發展出許多的合成方法來製作磁性奈米粒子。其中化學合成法一直是該領域的重點，因為此方法能夠控制奈米粒子的尺寸、形狀、組成以及表面的特性。為了能夠把磁性奈米粒子應用於生醫上，其中一個首要條件是製作出在正常的生理狀況下的水溶液介質中可分散且穩定的奈米粒子。然而，大多數化學合成的奈米材料因為其製作成本昂貴且對環境威脅高，因此所製作出來的奈米粒子也有可能對於病人會有潛在地毒性風險。相對地，事實證明使用天然性的材料能夠有更好的生物相容性以及較低的環境毒性。儘管已經開發出多種天然奈米粒子，但是想要製作出具有可再現性的品質

、高產率以及低成本的天然奈米粒子之製造技術仍然是一大挑戰。因此本次的研究將著重於使用化學及綠色合成法且能夠得到尺寸統一、分散以及穩定的磁性奈米粒子。並且使用傅里葉轉換紅外光譜(FT-IR)、X射線繞射儀(XRD)、掃描式電子顯微鏡(SEM)、穿透式電子顯微鏡(TEM)、動態光散射粒徑分析儀(DLS)、X射線光電子能譜儀(XPS)、振動樣品磁性量測儀(VSM)分析氧化鐵奈米粒子的表面形貌及化學結構。 對於化學合成法的磁性奈米粒子，研究出一種改良的溶劑熱合成法。探討改變不同參數對磁性奈米粒子的影響例如：鐵的來源、PSSMA的含量、去離子水的量和氫氧化鈉的量。結果指出，想要得到純鐵相需

要適量的水。PSSMA可以使合成後的磁性奈米粒子穩定從而抑制晶粒成長以及預防團聚。再者，還可以調控粒徑在120 - 220 nm之間。所有合成出的磁性奈米粒子在室溫中還會擁有超順磁的性質。在最佳條件則是附著在碳量子點上，而且結合後還顯現出良好的螢光特性。還進行了細胞增殖試驗，並發現具有生物相容性。此研究的第二部分，則是研究另一種方法，綠色合成法，使用了蘆薈來製造奈米粒子及其性質之研究。並且合成了其他的磁性奈米粒子，包含鈷和鎳。在XRD中分析出磁性奈米粒子的平均直徑在8 - 30 nm，而且有很好的結晶性。從SEM中看出明顯的球形結構，從TEM中看出 Fe3O4 顆粒較大、CoFe2O4 和 N

iFe2O4 顆粒較小。另外在SEM以及TEM中得到的尺寸和XRD計算的晶粒尺寸一致。每個奈米粒子的化學特性也證實合成都是成功的。並且磁性奈米粒子也顯示出生物可相容性及無毒性。為了更好地利用磁性納米粒子進行癌症治療，表面官能基化對於降低健康組織的細胞毒性、延長循環時間、專一性靶向癌細胞以及管控藥物傳遞的療法等因素至關重要。因此在第三部分，把合成的磁性奈米粒子成功地被PEG高分子包覆。選擇包覆PEG是為了防止蛋白質吸附，從而改善循環時間並最大限度地減少宿主對奈米顆粒的反應。最後，將被PEG包覆的磁性納米粒子與 Hedgehog Pathway Inhibitors drugs結合併在體內進行測試

。有趣的是，在藥物交聯後，觀察到癌細胞的活力急劇下降。共軛焦顯微鏡也用於觀察細胞與磁性奈米載體結合過程中的反應。從結果可以證實，隨著奈米載體濃度的增加，會誘導細胞凋亡。 有了Hh 信號通路與磁性納米粒子的卓越特性相結合後，將為研究成果轉化為新穎、更好、更安全的抗癌療法。

Liposome-Encapsulated Anthraquinone improves efficacy and safety in Triple Negative Breast Cancer

為了解決Caac report的問題，作者GEORGE, THOMASHIRE ANITA 這樣論述：

Background:Breast cancer is the most diagnosed cancer and a leading cause of cancer mortality in women worldwide. Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is highly heterogeneous, with high rates of relapse and distant metastasis, especially to the brain a

nd lung. Treatment of TNBC is a challenge because it lacks druggable targets and gene profiling shows six different subtypes which have distinct responses to different therapies.This shows that the ideal treatment strategy is the use of multi-targeting agents or a combination of agents.Drugs contain

ing anthraquinone scaffolds have shown to have enormous potential in cancer treatment and previous studies have shown that combining thiadiazole-fused anthraquinone scaffolds with other side chains expands the range of activities of the synthesized molecules, increasing its potency against several c

ancer cell lines.Small molecules are often limited by poor targeting and retention at tumor sites, as well as having poor pharmacokinetics. This leads to increased toxicity and rapid clearance from the bloodstream. Drug delivery carriers, such as liposomal formulations, can overcome these limitation

s, resulting in enhanced targeting, better efficacy, and reduced toxicity.Aim:The aim of this study is to develop a novel agent for TNBC therapy by screening a series of nitrogen-substituted anthra[1,2-c][1,2,5] thiadiazole-6,11-dione anthraquinone derivative small molecules. Upon selection of a sui

tably potent molecule, a drug delivery system will be formulated and characterized, aiming to improve drug therapeutic index and efficacy and, reduce toxicity.Materials and Methods:Eight in-house synthesized molecules were screened against two TNBC cell lines. Todetermine selectivity for breast canc

er cells one non-tumourigenic cell line was also used. Viability and cytotoxicity assays were performed, and “RV-59” was identified as the most suitable molecule. However, this molecule was poorly soluble in aqueous buffers and was relatively toxic to non-cancer cells. To overcome this, a liposome w

as developed which could encapsulate RV-59 with high efficiency and improve its activity. The liposome was formed using thin film hydration of lipids and cholesterol then sized by extrusion. The final liposomal formulation, LipoRV, was characterized by cryo-electron microscopy, dynamic light scatter

ing and dialysis to measure drug release. In-vitro assays were performed to compare LipoRV with the free molecule RV-59 and in-vivo studies were used to determine the therapeutic potential of LipoRV, as well as gather toxicity and safety data. RNA sequencing was used to examine the RV-59 mechanism o

f action and key differentially expressed proteins were confirmed by antibody array.Results:RV-59 was found to be one of the most potent molecules against both TNBC cell lines based on the in vitro screening. It was found to inhibit the cell cycle and induced necrosis and apoptosis. After liposome f

ormation, dynamic light scattering confirmed a single population of 91.02 ± 42.46 nm, PDI 0.081. Cryo-EM confirmed spherical uni-lamellar liposomes. LipoRV showed improved cell uptake and a four-fold increase in selectivity for cancer cells. It induced apoptosis and inhibited cell cycle readily and

demonstrated efficient inhibition of cell growth.In a TNBC xenograft mouse model, tumour volume was significantly reduced by LipoRVcompared to the free drug, clearing tumours in 85 % of animals. LipoRV also demonstrated an increased half-life and good safety profile compared to RV-59, without detrim

ental offtarget effects on organs or serum biochemical markers. Biodistribution analysis showed a higher drug serum concentration and reduced urinary output for LipoRV compared to RV-59.RNA sequencing of treated cells showed strong upregulation of cytokine and TNF-alphasignaling pathway and down reg

ulations genes related to extra cellular matrix components. A membrane-based antibody array confirmed the differential expression of multiple cytokines following LipoRV treatment.Conclusion:This study showed that encapsulating a thiadiazole-fused anthraquinone scaffold-basedmolecule into liposome gr

eatly improves its efficacy, reducing toxicity. This molecule shows immense potential for future use in TNBC therapy.