Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine
Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine
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DOI：
10.1002/advs.201801309
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发表时间：
2019-02-06
期刊：
影响因子：
15.1
通讯作者：
Behkam, Bahareh
中科院分区：
文献类型：
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作者：
Suh, SeungBeum;Jo, Ami;Behkam, Bahareh
由于纳米治疗药物的全身毒性和不充分的血管外运输到血管远端细胞，癌症药物递送仍然是一个艰巨的挑战。据推测，在缺乏外部驱动力的情况下，可以利用肠沙门氏菌血清型鼠伤寒沙门氏菌自主靶向递送纳米治疗药物到目前无法到达的部位。为了验证这一假设，研究人员开发了一种纳米级细菌自主给药系统（NanoBEADS），该系统将靶向肿瘤的鼠伤寒沙门氏菌VNP20009的功能与聚（乳酸-羟基甲酸）纳米颗粒结合在一起。研究了纳米颗粒偶联对纳米obeads在体外三维肿瘤球体中对癌细胞的侵袭和肿瘤内运输的影响，以及在体内乳腺肿瘤模型中的生物分布。研究发现，细胞间（细胞之间）的自我复制和易位是细菌在肿瘤内渗透的主要机制，纳米颗粒偶联并不妨碍细菌在肿瘤内的运输性能。通过开发新的运输指标，研究人员证明，在不需要任何外部驱动力或控制输入的情况下，nanobads可以将纳米颗粒在实体肿瘤中的保留和分布提高100倍。这种自主生物混合系统可以通过提高化疗药物的治疗指数和最大限度地减少全身副作用，为癌症治疗开辟一个强大的新范例。
Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria-enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor-targeting S. Typhimurium VNP20009 are interfaced with poly(lactic-co-glycolic-acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self-replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100-fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.