Independent of EPR Effect: A Smart Delivery Nanosystem for Tracking and Treatment of Nonvascularized Intra‐Abdominal Metastases,Advanced Functional Materials

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Independent of EPR Effect: A Smart Delivery Nanosystem for Tracking and Treatment of Nonvascularized Intra‐Abdominal Metastases
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-10-21 , DOI: 10.1002/adfm.201806162
Lingzhi Zhao ₁ , Wei Yuan ₂ , Junyao Li ₁ , Liqiang Yang ₁ , Yaoquan Su ₁ , Juanjuan Peng ₁ , Rui Chen ₂ , Huijun Phoebe Tham ₃ , Hongzhong Chen ₃ , Wei Qi Lim ₃ , Huijing Xiang ₃ , Pengyao Xing ₃ , Fuyou Li ₂ , Yanli Zhao _{3,

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Affiliation

Nanoparticle‐based delivery systems (NDS) have impacted the field of cancer therapy on account of the enhanced permeability and retention (EPR) effect that promotes passive accumulation in tumors through the tumor vasculature after intravenous (IV) administration. However, transplanted tumor xenografts on animal models used to justify the feasibility of EPR effect are quite different from clinical tumors in many aspects, a fact that becomes an impediment for NDS to succeed clinical trials. Particularly, early‐stage tumor metastases are usually nonvascularized and incapable of conforming the EPR effect after IV injection. Therefore, it is necessary to develop smart NDS to deliver drugs in an EPR‐independent route. Herein, an NDS‐based treatment approach for intra‐abdominal metastases from ovarian carcinoma is reported. Instead of IV injection, intraperitoneal (IP) injection was employed to directly apply the NDS to the metastatic lesions. The NDS was tailor‐made with targeting groups to actively target the tumor nidus and redox‐responsive drug release to reduce systematic toxicity. Comparing with IV administration, the IP injected NDS could be enriched in metastatic tumor more efficiently, leading to superior therapeutic outcome in vivo. This study provides a successful protocol of EPR‐independent NDS‐based cancer treatment, which may facilitate the clinical translation of nanoparticle‐based cancer therapeutics.

中文翻译：

不受EPR效应的影响：用于跟踪和治疗非血管化腹腔内转移的智能递送纳米系统

基于纳米颗粒的递送系统（NDS）由于增强的通透性和保留（EPR）效应，在静脉内（IV）给药后通过肿瘤脉管系统促进了肿瘤的被动蓄积，从而影响了癌症治疗领域。然而，在动物模型上移植的肿瘤异种移植物用于证明EPR效果的可行性，在许多方面与临床肿瘤有很大不同，这一事实成为NDS成功进行临床试验的障碍。特别是，早期肿瘤转移通常是无血管的，并且不能在静脉注射后达到EPR的效果。因此，有必要开发智能的NDS以独立于EPR的途径递送药物。本文报道了一种基于NDS的卵巢癌腹腔内转移治疗方法。代替静脉注射腹膜内（IP）注射直接将NDS应用于转移性病变。NDS是根据靶向组量身定制的，以主动靶向肿瘤病灶和氧化还原反应性药物释放，以降低系统毒性。与静脉注射相比，经IP注射的NDS可以更有效地富集转移性肿瘤，从而在体内具有出色的治疗效果。这项研究为基于EPR的基于NDS的癌症治疗提供了成功的方案，这可能有助于基于纳米颗粒的癌症治疗剂的临床翻译。IP注射的NDS可以更有效地富集转移性肿瘤，从而在体内产生卓越的治疗效果。这项研究为基于EPR的基于NDS的癌症治疗提供了成功的方案，这可能有助于基于纳米颗粒的癌症治疗剂的临床翻译。IP注射的NDS可以更有效地富集转移性肿瘤，从而在体内产生卓越的治疗效果。这项研究为基于EPR的基于NDS的癌症治疗提供了成功的方案，这可能有助于基于纳米颗粒的癌症治疗剂的临床翻译。

更新日期：2018-10-21

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