精準(zhǔn)調(diào)控免疫系統(tǒng)有望實(shí)現(xiàn)對(duì)腫瘤、自身免疫疾病、感染性疾病等多種疾病的有效防治。近年來多種免疫治療靶點(diǎn)及藥物的發(fā)現(xiàn)為精準(zhǔn)調(diào)控免疫系統(tǒng)治帶來了全新的機(jī)遇，但是藥物分子自身理化性質(zhì)導(dǎo)致的不穩(wěn)定性以及存在于組織、細(xì)胞、亞細(xì)胞層面的生理屏障嚴(yán)重妨礙了這些藥物分子有效作用于靶點(diǎn)從而制約療效。另一方面，非特異性的脫靶效應(yīng)也會(huì)帶來嚴(yán)重的毒副作用。本課題組致力于在藥物制劑和免疫治療的交叉領(lǐng)域展開系列研究來克服上述挑戰(zhàn)。主要研究方向包括：（1）設(shè)計(jì)開發(fā)可克服藥物不穩(wěn)定性及有關(guān)生理屏障的制劑；（2）調(diào)節(jié)制劑在多尺度（如組織、細(xì)胞、亞細(xì)胞）的時(shí)空分布并研究其與免疫應(yīng)答的相互關(guān)系；（3）探索制劑在不同疾病（如腫瘤、自身免疫疾病、感染性疾病）治療中的應(yīng)用并闡明其作用機(jī)制。
蒯銳博士長期致力于藥物制劑和免疫治療的交叉研究，通過“生物啟發(fā)”的策略構(gòu)建了一系列基于脂質(zhì)的納米制劑克服制約免疫治療的關(guān)鍵遞送瓶頸；闡明了這些制劑在組織、細(xì)胞、亞細(xì)胞等層面調(diào)控藥物遞送效率的關(guān)鍵原理；建立了相關(guān)制劑用于多種疾病防治的方法。早期成果孵化成立了一家名為“EVOQ Therapeutics”的初創(chuàng)公司。
2024 清華大學(xué)青教賽一等獎(jiǎng)
2024 清華大學(xué)藥學(xué)院優(yōu)秀教學(xué)獎(jiǎng)
2021 國家高層次人才青年項(xiàng)目
2018 中國教育部留學(xué)基金委“優(yōu)秀自費(fèi)留學(xué)生”
2017 美國藥物科學(xué)家協(xié)會(huì)(AAPS)生物技術(shù)創(chuàng)新獎(jiǎng)
2017 密歇根大學(xué)Norman Weiner 獎(jiǎng)學(xué)金
2015-2017 美國心臟協(xié)會(huì) (AHA) 獎(jiǎng)學(xué)金
2013 密歇根大學(xué)Broomfield 國際留學(xué)生獎(jiǎng)
2013 四川省優(yōu)秀碩士論文獎(jiǎng)
2011 石藥集團(tuán)優(yōu)秀學(xué)生獎(jiǎng)
代表性論文
1.Yu J, Li X, Li J, Sun N, Peng C, Huang J, Li S,
Kuai R*. Single-dose physically crosslinked hyaluronic acid and lipid hybrid nanoparticles containing cyclic guanosine monophosphate–adenosine monophosphate eliminate established tumors.
ACS Nano. 2024;18(43):29942-29955.
2.Li X, Wu C, Li J, Yu J, Yang X, Yu L, Wang C,
Kuai R*. An immunostimulatory liponanogel reveals immune activation-enhanced drug delivery and therapeutic efficacy in cancer.
Journal of Controlled Release. 2024;376:167-183.
3.He J, Wang C, Fang X, Li J, Shen X, Zhang J, Peng C, Li H, Li S, Karp J,
Kuai R*. Tuning the fluidity and protein corona of ultrasound-responsive liposomal nanovaccines to program T cell immunity in mice.
Nature Communications. 2024 ;15(1):8121.
4.Li J, Luo L, He J, Yu J, Li X, Shen X, Zhang J, Li S, Karp JM,
Kuai R*. A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors.
Cancer Research. 2024;84(14):2352-2363.
5.Li X#, Gao J#, Wu C, Wang C, Zhang R, He J, Xia ZJ, Joshi N*, Karp JM*,
Kuai R*. Precise modulation and use of reactive oxygen species for immunotherapy.
Science Advances. 2024;10(20):eadl0479.
6.Wang C, Zhang R, He J, Yu L, Li X, Zhang J, Li S, Zhang C, Kagan JC, Karp JM,
Kuai R*. Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity.
Nature Communications. 2023;14(1):3877.
7.Levy O#,
Kuai R#, Siren EM#, Bhere D, Milton Y, Nissar N, Debiasia M, Heinelt M, Abdi R, Alturki M, Fallatah M, Almalik A, Alhansan AH, Shah K, Karp JM. Shattering the glass ceiling of clinically meaningful mesenchymal stromal cell (MSC) therapies.
Science Advances, 2020, 6 (30), eaba6884.
8.
Kuai R, Sun X, Yuan W, Ochyl LJ, Xu Y, Najafabadi AH, Scheetz L, Yu M, Balwani I, Schwendeman A*, Moon JJ*. Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.
Journal of Controlled Release, 2018, 282, 131-139.
9.
Kuai R#, Yuan W#, Son S, Nam J, Xu Y, Fan Y, Schwendeman A*, Moon JJ*. Elimination of established tumors with nanodisc-based combination chemoimmunotherapy.
Science Advances. 2018; 4: eaao1736.
10.
Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A*, Moon JJ*. Designer vaccine nanodiscs for personalized cancer immunotherapy.
Nature Materials. 2017, 16 (4), 489-496.
11.
Kuai R, Li D, Chen YE, Moon JJ*, Schwendeman A*. High-density lipoproteins: nature’s multifunctional nanoparticles.
ACS Nano, 2016, 10 (3), 3015–3041.
書的章節(jié)
1.Luo L,
Kuai R*, Nanoparticles-assisted peptide cancer vaccine delivery. Cancer Vaccines, Methods in Molecular Biology, published by Springer Nature, 2025.
2.
Kuai R#, Ochyl LJ#, Schwendeman A*, Moon JJ*. Lipid-based nanoparticles for vaccine applications. Biomedical Engineering: Frontier Research and Converging Technologies. 2015, 9, 177-197.
