Poly(ethylene glycol) (PEG) is widely utilized as a hydrophilic coating to extend the circulation time and improve the tumor accumulation of polymeric micelles. Nonetheless, PEGylated micelles often activate complement proteins, leading to accelerated blood clearance and negatively impacting drug efficacy and safety. Here, we have crafted amphiphilic block copolymers that merge hydrophilic sulfoxide-containing polymers (psulfoxides) with the hydrophobic drug 7-ethyl-10-hydroxylcamptothecin (SN38) into drug-conjugate micelles. Our findings show that the specific variant, PMSEA-PSN38 micelles, remarkably reduce protein fouling, prolong blood circulation, and improve intratumoral accumulation, culminating in significantly increased anti-cancer efficacy compared with PEG-PSN38 counterpart. Additionally, PMSEA-PSN38 micelles effectively inhibit complement activation, mitigate leukocyte uptake, and attenuate hyperactivation of inflammatory cells, diminishing their ability to stimulate tumor metastasis and cause inflammation. As a result, PMSEA-PSN38 micelles show exceptional promise in the realm of anti-metastasis and significantly abate SN38-induced intestinal toxicity. This study underscores the promising role of psulfoxides as viable PEG substitutes in the design of polymeric micelles for efficacious anti-cancer drug delivery.

中文翻译：

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含亚砜聚合物缀合前药胶束，具有增强的抗癌活性和降低的肠道毒性


聚乙二醇（PEG）被广泛用作亲水涂层，以延长聚合物胶束的循环时间并改善肿瘤积聚。尽管如此，聚乙二醇化胶束通常会激活补体蛋白，导致血液清除加速并对药物功效和安全性产生负面影响。在这里，我们制作了两亲性嵌段共聚物，将亲水性含亚砜聚合物（p亚砜）与疏水性药物 7-乙基-10-羟基喜树碱（SN38）合并成药物缀合物胶束。我们的研究结果表明，与 PEG-PSN38 对应物相比，特定变体 PMSEA-PSN38 胶束可显着减少蛋白质污染、延长血液循环并改善瘤内蓄积，最终显着提高抗癌功效。此外，PMSEA-PSN38 胶束可有效抑制补体激活，减轻白细胞摄取，并减弱炎症细胞的过度激活，从而降低其刺激肿瘤转移和引起炎症的能力。因此，PMSEA-PSN38 胶束在抗转移领域显示出非凡的前景，并显着减轻 SN38 诱导的肠道毒性。这项研究强调了多亚砜作为可行的 PEG 替代品在聚合物胶束设计中的潜在作用，以实现有效的抗癌药物递送。