Background: Targeted nanocarriers can be used for reducing the unwanted side effects of drugs in non-target organs. Punicic acid, the polyunsaturated fatty acid of pomegranate seed oil, has been shown to possess anti-cancer effects on prostate cancer and the study also covers recent patents related to prostate cancer. The objective of the current study was to synthesize a co-polymeric micelle for delivery of Flutamide (FL) in prostate cancer using Polyacrylamide (PAM) and Punicic Acid (PA).

Methods: The co-polymer of PAM and PA was synthesized and conjugated to folic acid. The successful conjugation was studied computationally by the density functional theory method and was confirmed by the FT- IR and 1HNMR. The folate-PAMPA micelles produced by the film casting method were characterized physically. FL was loaded in the nanomicelles and its release test was done at different pH. The Critical Micelle Concentration (CMC) was measured by pyrene as a fluorescent probe. Their cellular uptake and cytotoxicity were evaluated on PC3 prostate cancer cells. The molecular geometry and vibrational frequencies of two different possibilities for conjugation were calculated using the B3LYP/6-31G basis set.

Results: The CMC of the micelles and their particle size were 79.05 μg/ml and 88 nm, respectively. The resulting nanocarriers of FL showed significantly more cytotoxic effects than the free drug at a concentration of 25 μM. The calculated results showed that the optimized geometries could well reproduce the structural parameters, and the theoretical vibrational frequencies were in good agreement with the experimental values.

Conclusion: Folate-PAMPA nanomicelles may be promising for the enhancement of FL cytotoxicity and seem to potentiate the effect of chemotherapeutic agents used in prostate cancer treatment.

背景：靶向纳米载体可用于减少药物对非靶器官的不良副作用。石榴籽油中的多不饱和脂肪酸石榴酸已被证明对前列腺癌具有抗癌作用，该研究还涵盖了与前列腺癌相关的最新专利。本研究的目的是合成一种共聚物胶束，用于使用聚丙烯酰胺 (PAM) 和石榴酸 (PA) 在前列腺癌中递送氟他胺 (FL)。

方法：合成PAM和PA的共聚物并与叶酸缀合。成功的共轭通过密度泛函理论方法进行了计算研究，并由 FT-IR 和 1HNMR 证实。对薄膜流延法生产的叶酸-PAMPA 胶束进行物理表征。FL 被加载到纳米胶束中，并在不同的 pH 值下进行释放测试。通过芘作为荧光探针测量临界胶束浓度 (CMC)。在 PC3 前列腺癌细胞上评估了它们的细胞摄取和细胞毒性。使用 B3LYP/6-31G 基组计算了两种不同共轭可能性的分子几何形状和振动频率。

结果：胶束的CMC及其粒径分别为79.05 μg/ml和88 nm。所得到的 FL 纳米载体在 25 μM 的浓度下显示出比游离药物显着更多的细胞毒性作用。计算结果表明，优化后的几何形状能够很好地再现结构参数，理论振动频率与实验值吻合较好。

结论：叶酸-PAMPA 纳米胶束可能有望增强 FL 细胞毒性，并且似乎可以增强用于前列腺癌治疗的化疗药物的效果。