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雜志名稱：Advanced Science
影響因子：15.1
文章題目：Dual Size/Charge-Switchable Nanocatalytic Medicine for Deep Tumor Therapy
文獻(xiàn)地址：https://doi.org/10.1002/advs.202002816
第一作者：Wencheng Wu, Yinying Pu, Jianlin Shi
作者單位：
中國(guó)科學(xué)院上海硅酸鹽研究所高性能陶瓷與超微結(jié)構(gòu)國(guó)家重點(diǎn)實(shí)驗(yàn)室；
中國(guó)科學(xué)院大學(xué)材料科學(xué)與光電工程中心；
上海市第十人民醫(yī)院超聲研究與教育研究所；
同濟(jì)大學(xué)腫瘤中心同濟(jì)大學(xué)醫(yī)學(xué)院醫(yī)學(xué)超聲科
引用產(chǎn)品： Dulbecco's modified eagle medium (DMEM high glucose)

文章摘要：

Elevating intratumoral levels of highly toxic reactive oxygen species (ROS) by nanocatalytic medicine for tumor-specific therapy without using conventional toxic chemodrugs is recently of considerable interest, which, however, still suffers from less satisfactory therapeutic efficacy due to the relatively poor accumulation at the tumor site and largely blocked intratumoral infiltration of nanomedicines. Herein, an ultrasound (US)-triggered dual size/charge-switchable nanocatalytic medicine, designated as Cu-LDH/HMME@Lips, is constructed for deep solid tumor therapy via catalytic ROS generations. The negatively charged liposome outer-layer of the nanomedicine enables much-prolonged blood circulation for significantly enhanced tumoral accumulation, while the positively charged Fenton-like catalyst Cu-LDH released from the liposome under the US stimulation demonstrates much enhanced intratumoral penetration via transcytosis. In the meantime, the co-released sonosensitizer hematoporphyrin monomethyl ether (HMME) catalyze the singlet oxygen (1O2) generation upon the US irradiation, and deep-tumoral infiltrated Cu-LDH catalyzes the H2O2 decomposition to produce highly toxic hydroxyl radical (·OH) specifically within the mildly acidic tumor microenvironment (TME). The efficient intratumoral accumulation and penetration via the dual size/charge switching mechanism, and the ROS generations by both sonosensitization and Fenton-like reactions, ensures the high therapeutic efficacy for the deep tumor therapy by the nanocatalytic medicine.

在不使用常規(guī)毒性化學(xué)藥物的情況下，通過(guò)納米催化藥物提高腫瘤內(nèi)高毒性活性氧(ROS)水平，以進(jìn)行腫瘤特異性治療，近年來(lái)引起了人們的極大興趣，然而，由于納米藥物在腫瘤部位的積累相對(duì)較差，并且在很大程度上阻斷了腫瘤內(nèi)的浸潤(rùn)，其治療效果仍不盡如人意。本文構(gòu)建了一種超聲(US)觸發(fā)雙尺寸/電荷可切換的納米催化藥物，命名為Cu-LDH/HMME@Lips，通過(guò)催化ROS世代用于深部實(shí)體腫瘤治療。納米藥物外層帶負(fù)電荷的脂質(zhì)體可以延長(zhǎng)血液循環(huán)，從而顯著增強(qiáng)腫瘤積聚，而在US刺激下，脂質(zhì)體釋放的帶正電荷的fenton樣催化劑Cu-LDH通過(guò)胞吞作用增強(qiáng)了腫瘤內(nèi)的滲透。同時(shí)，協(xié)同釋放的聲敏劑血卟啉單甲基醚(HMME)在US照射下催化單線態(tài)氧(1O2)生成，腫瘤深部浸潤(rùn)的Cu-LDH催化H2O2分解，在輕度酸性腫瘤微環(huán)境(TME)內(nèi)特異性產(chǎn)生高毒羥基自由基(·OH)。通過(guò)雙大小/電荷開(kāi)關(guān)機(jī)制在腫瘤內(nèi)的高效蓄積和滲透，以及超聲敏化和芬頓樣反應(yīng)的ROS生成，確保了納米催化藥物對(duì)深部腫瘤的高療效。