TumorSelect® is an anticancer technology that combines cytotoxics, nanotechnology, and knowledge of human physiology to develop innovative therapeutic interventions with minimal undesirable side effects commonly observed in conventional chemotherapy. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Several designer prodrugs are incorporated within pseudo-LDL nanoparticles, which carry them to tumor tissues, are taken up, internalized, transformed into active drugs, and inhibit cancer cell proliferation. Highly lipophilic prodrug conjugates of paclitaxel suitable for incorporation into the pseudo-LDL nanoparticles of the TumorSelect® delivery vehicle formulation were designed, synthesized, and evaluated in the panel of 24-h NCI-60 human tumor cell line screening to demonstrate the power of such an innovative approach. Taxane prodrugs, viz., ART-207 was synthesized by tethering paclitaxel to lipid moiety with the aid of a racemic solketal as a linker in cost-effective, simple, and straightforward synthetic transformations. In addition to the typical 24-h NCI screening protocol, these compounds were assessed for growth inhibition or killing of ovarian cell lines for 48 and 72h-time intervals and identified the long-lasting effectiveness of these lipophilic prodrugs. All possible, enantiomerically pure isomers of ART-207 were also synthesized, and cytotoxicities were biosimilar to racemic ART-207, suggesting that enantiopurity of linker has a negligible effect on cell proliferation. To substantiate further, ART-207 was evaluated for its in vivo tumor reduction efficacy by studying the xenograft model of ovarian cancer grown in SCID mice. Reduced weight loss (a measure of toxicity) in the ART-207 group was observed, even though it was dosed at 2.5x the paclitaxel equivalent of Abraxane®. As a result, our delineated approach is anticipated to improve patient quality of life, patient retention in treatment regimes, post-treatment rapid recovery, and overall patient compliance without compromising the efficacy of the cytotoxic promiscuous natural products.

TumorSelect® 是一种抗癌技术，它结合了细胞毒剂、纳米技术和人体生理学知识，以开发创新的治疗干预措施，并将常规化疗中常见的不良副作用降至最低。肿瘤对胆固醇有贪婪的胃口，这促进了肿瘤的生长并促进了它们的增殖。我们已经将这种需求转变为一种隐形递送系统，在人体和肿瘤细胞的帮助下伪装和递送抗癌药物。几种设计的前药被掺入假低密度脂蛋白纳米颗粒中，这些纳米颗粒将它们携带到肿瘤组织中，被吸收、内化、转化为活性药物，并抑制癌细胞增殖。在 24 小时 NCI-60 人肿瘤细胞系筛选小组中设计、合成和评估了适合掺入 TumorSelect® 递送载体制剂的假低密度脂蛋白纳米颗粒的紫杉醇高亲脂性前药偶联物，以证明此类药物的功效一种创新的方法。紫杉烷前药，即，ART-207是通过将紫杉醇连接到脂质部分并借助外消旋溶胶作为接头在成本效益、简单和直接的合成转化中合成的。除了典型的 24 小时 NCI 筛选方案外，还以 48 和 72 小时的时间间隔评估了这些化合物对卵巢细胞系的生长抑制或杀伤作用，并确定了这些亲脂性前药的持久有效性。还合成了ART-207的所有可能的对映纯异构体，并且细胞毒性与外消旋ART-207具有生物相似性，这表明接头的对映纯度对细胞增殖的影响可以忽略不计。为了进一步证实，ART-207被评估为通过研究在 SCID 小鼠中生长的卵巢癌异种移植模型的体内肿瘤减少功效。在ART-207组中观察到体重减轻（一种毒性指标）减少，即使它的剂量是 Abraxane® 紫杉醇当量的 2.5 倍。因此，我们描述的方法有望改善患者的生活质量、患者在治疗方案中的保留、治疗后的快速恢复和患者的整体依从性，而不会影响细胞毒性混杂天然产品的功效。