Thermosensitive Exosome-Liposome Hybrid Nanoparticle-Mediated Chemoimmunotherapy for Improved Treatment of Metastatic Peritoneal Cancer.
Thermosensitive Exosome-Liposome Hybrid Nanoparticle-Mediated Chemoimmunotherapy for Improved Treatment of Metastatic Peritoneal Cancer.
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热敏外泌体-脂质体混合纳米颗粒介导的化学免疫疗法可改善转移性腹膜癌的治疗
DOI：
10.1002/advs.202000515
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Lv Q;Cheng L;Lu Y;Zhang X;Wang Y;Deng J;Zhou J;Liu B;Liu J
转移性腹膜癌是一种致死性疾病，目前尚无有效的治疗方法。为了改善这种疾病的治疗，最近开发的热腹腔内化疗（HIPEC）已成为护理标准。然而，这种方法的功效受到低效药物渗透和快速发展的耐药性的限制。在此，报道了一种纳米技术方法，其设计用于改善药物向mPC的递送，并通过递送化学免疫疗法来增强HIPEC的功效。首先，确定HIPEC的药物递送效率，并且发现化疗剂不能有效地递送到大的肿瘤结节。为了克服递送障碍，然后合成基因工程外泌体-热敏脂质体混合NP或gETL NP，并且证明了静脉内施用后的NP有效地渗透到mPC肿瘤中并在HIPEC的低温条件下释放有效载荷。最后，研究表明，当粒细胞-巨噬细胞集落刺激因子（GM-CSF）和多西他赛共同递送时，gETL NP有效抑制肿瘤发展，并且当HIPEC共同施用时，功效增强。该研究提供了一种改善药物递送至mPCs的策略，并提供了一种有希望的方法，通过将HIPEC的局部递送和经由gETL NP的化学免疫疗法的全身递送相结合来改善疾病的治疗。在这项研究中，开发了一种用于粒细胞-巨噬细胞集落刺激因子（GM-CSF）和多西他赛共递送的CD 47过表达外泌体-脂质体混合纳米颗粒（gETL NP）递送系统。结合标准的腹腔热化疗（HIPEC）治疗转移性腹膜癌（mPC），gETL NP实现HIPEC介导的化疗和CD 47和GM-CSF介导的免疫治疗。
Metastatic peritoneal carcinoma (mPC) is a deadly disease without effective treatment. To improve treatment of this disease, a recently developed hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as the standard of care. However, the efficacy of this approach is limited by inefficient drug penetration and rapidly developed drug resistance. Herein, a nanotechnology approach is reported that is designed to improve drug delivery to mPC and to augment the efficacy of HIPEC through delivery of chemoimmunotherapy. First, the drug delivery efficiency of HIPEC is determined and it is found that chemotherapy agents cannot be efficiently delivered to large tumors nodules. To overcome the delivery hurdle, genetically engineered exosomes‐thermosensitive liposomes hybrid NPs, or gETL NPs, are then synthesized, and it is demonstrated that the NPs after intravenous administration efficiently penetrates into mPC tumors and releases payloads at the hypothermia condition of HIPEC. Last, it is shown that, when granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and docetaxel are co‐delivered, gETL NPs effectively inhibit tumor development and the efficacy is enhanced when HIPEC is co‐administered. The study provides a strategy to improve drug delivery to mPCs and offers a promising approach to improve treatment of the disease through combination of locoregional delivery of HIPEC and systemic delivery of chemoimmunotherapy via gETL NPs. In this study, a CD47 over expressed exosomes–liposomes hybrid nanoparticle (gETL NP) delivery system is developed for granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and docetaxel co‐delivery. Combined with standard hyperthermic intraperitoneal chemotherapy (HIPEC) therapy to metastatic peritoneal carcinoma (mPC), the gETL NP achieves HIPEC‐mediated chemotherapy and CD47‐ and GM‐CSF‐mediated immunotherapy.
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影响因子：
82.9
作者：
Liu X;Pu Y;Cron K;Deng L;Kline J;Frazier WA;Xu H;Peng H;Fu YX;Xu MM
通讯作者：
Xu MM
影响因子：
8.8
作者：
Ansaloni, L.;Coccolini, F.;Morosi, L.;Ballerini, A.;Ceresoli, M.;Grosso, G.;Bertoli, P.;Busci, L. M.;Lotti, M.;Cambria, F.;Pisano, M.;Rossetti, D.;Frigerio, L.;D'Incalci, M.;Zucchetti, M.
通讯作者：
Zucchetti, M.
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
45.3
作者：
Elias, Dominique;Gilly, Francois;Glehen, Olivier
通讯作者：
Glehen, Olivier
影响因子：
28.1
作者：
Kulkarni, Ashish;Chandrasekar, Vineethkrishna;Sengupta, Shiladitya
通讯作者：
Sengupta, Shiladitya