Drug resistance and relapse is common in cancer treatments with chemotherapeutics, and while drug combinations with naturally occurring, differentiation-inducing retinoic acid (RA) provide remission-free cures for one type of liquid tumor, solid tumors present major problems for delivery. Here, inspired by filoviruses that can be microns in length, flexible filomicelles that self-assemble from an amphiphilic block copolymer (PEG–PCL) are shown to effectively deliver RA and paclitaxel (TAX) to several solid tumor models, particularly in the liver. These hydrophobic compounds synergistically load into the cores of the elongated micelles, and the coloaded micelles prove most effective at causing cell death, ploidy, and durable regression of tumors compared to free drugs or to separately loaded drugs. RA-TAX filomicelles also reduce mortality of human lung or liver derived cancers engrafted at liver, intraperitoneal, and subcutaneous sites in immunodeficient mice. In vitro studies show that the dual drug micelles effectively suppress proliferation while upregulating a generic differentiation marker. The results highlight the potency of dual-loaded filomicelles in killing cancer cells or else driving their differentiation away from growth.

中文翻译：

---

Filomicelles提供紫杉醇和视黄酸的化学分化组合，可持久抑制肝癌以延长生存期。

在化学疗法的癌症治疗中，耐药性和复发很常见，并且与天然存在的，诱导分化的视黄酸（RA）结合使用的药物可为一种类型的液体肿瘤提供无缓解的治愈方法，而实体瘤则是递送的主要问题。在这里，受到长度可能为微米的线状病毒的启发，由两亲性嵌段共聚物（PEG-PCL）自组装的柔性丝状细胞被证明可以有效地将RA和紫杉醇（TAX）递送至多种实体瘤模型，尤其是在肝脏中。这些疏水化合物协同加载到细长胶束的核心中，并且与游离药物或单独加载的药物相比，共加载的胶束在引起肿瘤的细胞死亡，倍性和持久消退方面被证明是最有效的。RA-TAX丝状细胞还可以降低免疫缺陷小鼠肝脏，腹膜内和皮下部位移植的人肺或肝源性癌症的死亡率。体外研究表明，双重药物胶束可有效抑制增殖，同时上调通用分化标记。结果突出了双重加载的丝状细胞在杀死癌细胞或驱使它们的分化远离生长方面的潜能。