Abstract：
Breast cancer (BC) is the most common malignancy among females worldwide, and its high metastasis rates are the leading cause of death just after lung cancer. Currently, tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA that has shown potential anticancer activity against BC, but the non-targeted delivery has serious side effects that limit its ubiquitous utility. Therefore, releasing anti-cancer drugs precisely to the tumor site can improve efficacy and reduce the side effects on the body. Nanotechnology has emerged as one of the most important strategies to solve the issue of overdose TAM toxicity, owing to the ability of nano-enabled formulations to deliver desirable quantity of TAM to cancer cells over a longer period of time. In view of this, use of fluorescent carbon nanoparticles in targeted drug delivery holds novel promise for improving the efficacy, safety, and specificity of TAM therapy. Here, we synthesized biocompatible carbon nanoparticles (CNPs) using chitosan molecules without any toxic surface passivating agent. Synthesized CNPs exhibit good water dispersibility and emit intense blue fluorescence upon excitation (360 nm source). The surface of the CNPs has been functionalized with folate using click chemistry to improve the targeted drug uptake by the malignant cell. The pH difference between cancer and normal cells was successfully exploited to trigger TAM release at the target site. After six hours of incubation, CNPs released ∼ 74 % of the TAM drug in acidic pH. In vitro, studies have also demonstrated that after treatment with the synthesized CNPs, significant inhibition of the tumor growth could be achieved.
摘要：
乳腺癌（BC）是全球女性中最常见的恶性肿瘤，高转移率是肺癌后死亡的主要原因。目前,他莫昔芬（TAM）是一种疏水性抗癌剂和选择性雌激素调节剂（SERM），由FDA批准，已显示出针对BC的潜在抗癌活性，但是非定向递送具有严重的副作用，限制了其无处不在的效用。因此,将抗癌药物精确释放到肿瘤部位，可以提高疗效，减少对身体的副作用。纳米技术已成为解决过量TAM毒性问题的最重要策略之一，由于纳米使能的制剂能够在更长的时间内向癌细胞递送所需量的TAM。鉴于此,在靶向药物递送中使用荧光碳纳米颗粒为提高疗效提供了新的希望，安全,和TAM治疗的特异性。这里,我们合成的生物相容性碳纳米颗粒（CNPs）使用壳聚糖分子没有任何有毒的表面钝化剂。合成的CNP表现出良好的水分散性,并且在激发(360nm源)时发出强烈的蓝色荧光。已经使用点击化学用叶酸将CNP的表面官能化,以改善恶性细胞的靶向药物摄取。成功利用癌细胞和正常细胞之间的pH差异来触发靶位点的TAM释放。经过6个小时的孵化,CNP在酸性pH下释放约74%的TAM药物。体外，研究还表明，用合成的CNPs治疗后，可以实现对肿瘤生长的显著抑制。
