Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan; Department of Surgery, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan.
J Control Release. 2017 May 28;254:119-130. doi: 10.1016/j.jconrel.2017.03.035. Epub 2017 Mar 21.
Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. The nanoparticle (NP) payload was obtained from co-assembly of poly(γ-glutamic acid-co-distearyl γ-glutamate) with poly(lactic-co-glycolic acid), paclitaxel (PTX), and oleic acid-coated superparamagnetic iron oxide NPs in aqueous solution. The particle size and drug loading content were ca 110nm and 8.4wt%, respectively. After being engulfed by ADSCs, the nanotherapeutics was found rather harmless to cellular hosts at a PTX concentration of 30μM over 48h in the absence of pertinent stimulus. Nevertheless, the ADSC-based approach combined with high frequency magnetic field exhibits a sound therapeutic performance with a 4-fold increase in therapeutic index on brain astrocytoma (ALTS1C1)-bearing mice (C57BL/6J) as compared to the typical chemotherapy using a current first-line chemodrug, temozolomide. Immunohistochemical examination of brain tumor sections confirms the successful cellular transport and pronounced cytotoxic action of therapeutics against tumor cells in vivo. This work demonstrates the promise of ADSC-mediated chemo/thermal therapy against brain tumors.
化疗通常用于治疗恶性脑肿瘤,特别是对于手术无法到达的肿瘤区域。然而,由于血脑屏障(BBB)的存在,临床治疗的肿瘤积累和治疗效果仍然令人担忧。为此,我们提出了一种突出的治疗策略,采用脂肪来源的干细胞(ADSCs),能够选择性地携带纳米治疗有效载荷,针对脑肿瘤进行热/化疗。纳米颗粒(NP)有效载荷是通过聚(γ-谷氨酸-co-二硬脂酰基γ-谷氨酸)与聚(乳酸-co-乙醇酸)、紫杉醇(PTX)和油酸包覆的超顺磁性氧化铁 NPs 在水溶液中共组装获得的。粒径和药物负载含量分别约为 110nm 和 8.4wt%。ADSCs 吞噬纳米药物后,在无相关刺激的情况下,细胞宿主在 30μM 的 PTX 浓度下,48 小时内纳米药物的毒性非常小。然而,与使用当前一线化疗药物替莫唑胺的典型化疗相比,ADSC 联合高频磁场的方法对携带脑星形细胞瘤(ALTS1C1)的小鼠(C57BL/6J)具有良好的治疗效果,治疗指数提高了 4 倍。对脑肿瘤切片的免疫组织化学检查证实了治疗剂在体内对肿瘤细胞的成功细胞转运和明显的细胞毒性作用。这项工作证明了 ADSC 介导的化疗/热疗对脑肿瘤的应用前景。
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