Nanotechnology-mediated immunochemotherapy combined with docetaxel and PD-L1 antibody increase therapeutic effects and decrease systemic toxicity

被引:79
作者
Gu, Zili [1 ]
Wang, Qingjie [2 ]
Shi, Yanbin [3 ]
Huang, Yi [1 ]
Zhang, Jing [4 ]
Zhang, Xinke [5 ]
Lin, Guimei [1 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Qilu Hosp, Inst Basic Med Sci, Jinan 250012, Shandong, Peoples R China
[3] Qilu Univ Technol, Shandong Acad Sci, Sch Mech & Automot Engn, Jinan 250353, Shandong, Peoples R China
[4] Jiangxi Univ Tradit Chinese Med, Minist Educ, Key Lab Modern Preparat TCM, Nanchang 330004, Jiangxi, Peoples R China
[5] Shandong Univ, Sch Pharmaceut Sci, Drug Screening Unit Platform, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Nanotechnology; Liposome; Docetaxel; PD-L1; Immunochemotherapy; IMMUNE CHECKPOINT BLOCKADE; PH-SENSITIVE LIPOSOMES; ANTI-PD-L1; ANTIBODY; CANCER-CELLS; IMMUNOTHERAPY; COMBINATION; DELIVERY; NANOPARTICLES; BIOMARKERS; MECHANISM;
D O I
10.1016/j.jconrel.2018.08.011
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Immunotherapy has exhibited enormous practice in the treatment of melanoma because of the intrinsic properties of tumor. Tumor can downmodulate immune function via multiple mechanisms such as immune checkpoint pathways. The PD-L1 monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells to evade an immune attack, can delay tumor growth efficiently with inevitable disadvantages such as low selectivity and systemic toxicity. Nanomedicine is clearly an approach that holds tremendous potential for addressing the shortcomings and assisting delivery of drugs with proper biodistribution. Herein, we developed a smart nanoplatform with precisely active targeting liposome co-loaded chemotherapy and immunotherapy drugs for synergistic antitumor effects while decreasing systemic toxicity. Immunoliposomes have stable pharmaceutical properties and show a significant antitumor effect in vivo and in vitro. Cellular uptake in vitro and biodistribution in vivo demonstrated that immunoliposomes could be delivered and accumulated more in tumor tissues. These immunoliposomes exhibited effective tumor inhibition and prolonged survival time due to activation of tumor-specific CD8+ T cell and highly selective tumor killing. In addition, safety evaluation of lipo-somes also demonstrated their increased tumor accumulation and decreased systemic toxicity. Hence, this smart pH-sensitive nanoplatform has promising potential for clinical applications and possibly provides a well-controlled design for combination of chemotherapy with various immunotherapies for further exploration.
引用
收藏
页码:369 / 380
页数:12
相关论文
共 31 条
[1]   Liposomal drug delivery systems: From concept to clinical applications [J].
Allen, Theresa M. ;
Cullis, Pieter R. .
ADVANCED DRUG DELIVERY REVIEWS, 2013, 65 (01) :36-48
[2]   Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin [J].
Arabi, Leila ;
Badiee, Ali ;
Mosaffa, Fatemeh ;
Jaafari, Mahmoud Reza .
JOURNAL OF CONTROLLED RELEASE, 2015, 220 :275-286
[3]   Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology [J].
Bertrand, Nicolas ;
Wu, Jun ;
Xu, Xiaoyang ;
Kamaly, Nazila ;
Farokhzad, Omid C. .
ADVANCED DRUG DELIVERY REVIEWS, 2014, 66 :2-25
[4]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[5]   Granzymes in cancer and immunity [J].
Cullen, S. P. ;
Brunet, M. ;
Martin, S. J. .
CELL DEATH AND DIFFERENTIATION, 2010, 17 (04) :616-623
[6]   Combinatorial prospects of nano-targeted chemoimmunotherapy [J].
Da Silva, C. G. ;
Rueda, Felix ;
Lowik, C. W. ;
Ossendorp, Ferry ;
Cruz, Luis J. .
BIOMATERIALS, 2016, 83 :308-320
[7]  
Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
[8]   Combination of using prodrug-modified cationic liposome nanocomplexes and a potentiating strategy via targeted co-delivery of gemcitabine and docetaxel for CD44-overexpressed triple negative breast cancer therapy [J].
Fan, Yang ;
Wang, Qingjie ;
Lin, Guimei ;
Shi, Yanbin ;
Gu, Zili ;
Ding, Tingting .
ACTA BIOMATERIALIA, 2017, 62 :257-272
[9]   Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug delivery [J].
Fay, Francois ;
McLaughlin, Kirsty M. ;
Small, Donna M. ;
Fennell, Dean A. ;
Johnston, Patrick G. ;
Longley, Daniel B. ;
Scott, Christopher J. .
BIOMATERIALS, 2011, 32 (33) :8645-8653
[10]   Combinatorial immunotherapy for melanoma [J].
George, D. D. ;
Armenio, V. A. ;
Katz, S. C. .
CANCER GENE THERAPY, 2017, 24 (03) :141-147