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近日，華中農(nóng)業(yè)大學(xué)韓鶴友教授團(tuán)隊(duì)與新加坡南洋理工大學(xué)趙彥利教授、華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬協(xié)和醫(yī)院副主任醫(yī)師梁華庚合作，針對(duì)臨床上常用的光聲試劑在注入腫瘤病人體內(nèi)后一直保持常開（always on）狀態(tài)的早期診斷及治療瓶頸，設(shè)計(jì)了一種原位納米酶放大的近紅外II腫瘤精準(zhǔn)治療平臺(tái)，實(shí)現(xiàn)了對(duì)乳腺癌的化學(xué)動(dòng)力學(xué)和光熱聯(lián)合治療。相關(guān)研究成果以“In Situ Nanozyme-Amplified NIR-II Phototheranostics for Tumor-Specific Imaging and Therapy”為題在Advanced Functional Materials發(fā)表。

近紅外二區(qū)（NIR-II）腫瘤光療技術(shù)，由于其較強(qiáng)的穿透深度、較高的空間分辨率和無(wú)創(chuàng)傷性等優(yōu)點(diǎn)，在納米醫(yī)學(xué)中具有巨大的應(yīng)用前景。但是，目前“常開”光療劑往往有許多不良副作用，阻礙了其臨床試驗(yàn)的進(jìn)展。為了克服這一瓶頸，研究團(tuán)隊(duì)開發(fā)了一種原位納米酶放大顯色納米反應(yīng)器，將3,3',5,5'-四甲基聯(lián)苯胺（TMB）和超小型PtAu納米顆粒負(fù)載于金屬有機(jī)框架，用于特定的乳腺癌腫瘤治療，同時(shí)保護(hù)了正常組織不受損傷。作為一種智能光聲診斷試劑，構(gòu)建的納米反應(yīng)器通過H2O2激活和酸增強(qiáng)狀態(tài)，打開光聲信號(hào)，對(duì)腫瘤部位進(jìn)行術(shù)前的精準(zhǔn)定位和診斷。作為一種納米酶，腫瘤組織的特殊微環(huán)境引發(fā)活性氧對(duì)其進(jìn)行催化損傷，實(shí)現(xiàn)化學(xué)動(dòng)力學(xué)治療（CDT）。同時(shí)，被氧化的TMB對(duì)腫瘤組織進(jìn)行光熱療法（PTT），實(shí)現(xiàn)了CDT和PTT最佳組合的“一體式”聯(lián)合治療。本研究中的納米酶可對(duì)腫瘤進(jìn)行特異性消融，有望在腫瘤治療中進(jìn)一步開發(fā)智能納米酶。

TMPAs的酶活性及催化機(jī)理

TMPAs的體外協(xié)同抗癌作用

TMPAs的體內(nèi)光聲成像診斷

該研究通過原位納米酶放大策略，為腫瘤的精準(zhǔn)治提供了新的方法。體外和體內(nèi)試驗(yàn)均表明，該原位納米酶放大的近紅外二區(qū)腫瘤精準(zhǔn)治療平臺(tái)能夠準(zhǔn)確有效地消融腫瘤，實(shí)現(xiàn)了對(duì)乳腺癌的CDT-PTT聯(lián)合治療，同時(shí)對(duì)正常組織的非特異性損傷非常小或免受損傷。

華中農(nóng)業(yè)大學(xué)博士研究生馬召玉為該文章第一作者，華中農(nóng)業(yè)大學(xué)韓鶴友教授、新加坡南洋理工大學(xué)趙彥利教授和華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬協(xié)和醫(yī)院梁華庚醫(yī)師為該論文的共同通訊作者，華中農(nóng)業(yè)大學(xué)為成果第一單位。該研究得到了國(guó)家自然科學(xué)基金等項(xiàng)目的資助。

【英文摘要】

The discovery of near-infrared-II (NIR-II) tumor phototheranostics holds a great promise for use in nanomedicine on account of its enhanced penetration depth, high spatial resolution, and noninvasiveness. However, contemporary "always on" phototherapeutic agents often have many undesirable side effects that hinder their clinical trial progress. To overcome this dilemma, an in situ nanozyme-amplified chromogenic nanoreactor by loading 3,3′,5,5′-tetramethylbenzidine (TMB) and ultrasmall PtAu nanoparticles into a metal-organic framework is developed for specific tumor theranostics, leaving normal tissues unharmed. As an intelligent photoacoustic diagnostic agent, the as-constructed nanoreactor remains silent until they enter the tumor site (H2O2-activated and acid-enhanced conditions) and turns on photoacoustic signal to render a preoperative tumor diagnosis. As a nanozyme, the special microenvironment of the tumor tissue is used to initiate its catalytic damage by reactive oxygen species for chemodynamic therapy (CDT). More importantly, the TMB is oxidized, and the subsequent photothermal therapy (PTT) can be realized leading to an optimal combination of CDT and PTT to concurrently fight obstinate cancers. The present “all-in-one” phototheranostics utilize nanozyme-augmented NIR-II agents for specific tumor ablation, which are promising for further development of intelligent nanozymes in the tumor therapy.

論文鏈接：https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202103765