Tailoring polymeric hybrid micelles with lymph node targeting ability to improve the potency of cancer vaccines

被引:105
作者
Zeng, Qin [1 ]
Li, Hanmei [1 ]
Jiang, Hao [1 ]
Yu, Jiao [1 ]
Wang, Ying [1 ]
Ke, Huan [1 ]
Gong, Tao [1 ]
Zhang, Zhirong [1 ]
Sun, Xun [1 ]
机构
[1] Sichuan Univ, Key Lab Drug Targeting & Drug Delivery Syst, West China Sch Pharm, Minist Educ, Chengdu 17 Sect,3 Renmin South Rd, Chengdu 610041, Peoples R China
基金
中国国家自然科学基金;
关键词
Polymeric hybrid micelles; Lymph node; Targeting; Cytotoxic T lymphocytes; Melanoma; Vaccine; DENDRITIC CELLS; IN-VIVO; CELLULAR-IMMUNITY; IMMUNOSTIMULATORY OLIGONUCLEOTIDES; NANOPARTICLE VACCINES; DUAL-DELIVERY; TRP2; PEPTIDE; ACTIVATION; LIPOSOMES; RESPONSES;
D O I
10.1016/j.biomaterials.2017.01.010
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions. We successfully encapsulate melanoma antigen peptide Trp2 and Toll-like receptor-9 (TLR-9) agonist CpG ODN into HMs with a size of sub-30 nm. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by simply adjusting the molar ratio of PEG-PE and PSA. Our results demonstrated the optimized HMs with an equal mol of PEG PE and PSA can potently target proximal LNs where their cargos are efficiently internalized by DCs. Furthermore, HMs mediated Trp2/CpG delivery system greatly expands antigen specific cytotoxic T lymphocytes (CTLs) and offers a strong anti-tumor effect in a lung metastatic melanoma model. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:105 / 113
页数:9
相关论文
共 34 条
[21]   Cancer immunotherapy via dendritic cells [J].
Palucka, Karolina ;
Banchereau, Jacques .
NATURE REVIEWS CANCER, 2012, 12 (04) :265-277
[22]  
Reddy ST, 2007, NAT BIOTECHNOL, V25, P1159, DOI [10.1038/nbt1332, 10.1038/nbtl332]
[23]   In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles [J].
Reddy, ST ;
Rehor, A ;
Schmoekel, HG ;
Hubbell, JA ;
Swartz, MA .
JOURNAL OF CONTROLLED RELEASE, 2006, 112 (01) :26-34
[24]   Adjuvant activity of CpG-ODN formulated as a liquid crystal [J].
Sanchez Vallecillo, Maria F. ;
Ullio Gamboa, Gabriela V. ;
Palma, Santiago D. ;
Harman, Maria F. ;
Chiodetti, Ana L. ;
Moron, Gabriel ;
Allemandi, Daniel A. ;
Pistoresi-Palencia, Maria C. ;
Maletto, Belkys A. .
BIOMATERIALS, 2014, 35 (08) :2529-2542
[25]   Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides [J].
Tao, Yu ;
Zhang, Yan ;
Ju, Enguo ;
Ren, Hui ;
Ren, Jinsong .
NANOSCALE, 2015, 7 (29) :12419-12426
[26]   From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity [J].
Trevaskis, Natalie L. ;
Kaminskas, Lisa M. ;
Porter, Christopher J. H. .
NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (11) :781-803
[27]   Pegylated Phospholipid Micelles Induce Endoplasmic Reticulum-Dependent Apoptosis of Cancer Cells but not Normal Cells [J].
Wang, Jing ;
Fang, Xiaocui ;
Liang, Wei .
ACS NANO, 2012, 6 (06) :5018-5030
[28]   A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study [J].
Wiedermann, Ursula ;
Wiltschke, C. ;
Jasinska, J. ;
Kundi, M. ;
Zurbriggen, R. ;
Garner-Spitzer, E. ;
Bartsch, R. ;
Steger, G. ;
Pehamberger, H. ;
Scheiner, O. ;
Zielinski, C. C. .
BREAST CANCER RESEARCH AND TREATMENT, 2010, 119 (03) :673-683
[29]   pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides [J].
Wilson, John T. ;
Keller, Salka ;
Manganiello, Matthew J. ;
Cheng, Connie ;
Lee, Chen-Chang ;
Opara, Chinonso ;
Convertine, Anthony ;
Stayton, Patrick S. .
ACS NANO, 2013, 7 (05) :3912-3925
[30]   Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis [J].
Xu, Zhenghong ;
Ramishetti, Srinivas ;
Tseng, Yu-Cheng ;
Guo, Shutao ;
Wang, Yuhua ;
Huang, Leaf .
JOURNAL OF CONTROLLED RELEASE, 2013, 172 (01) :259-265