TY - JOUR
T1 - Large-Pore Mesoporous-Silica-Coated Upconversion Nanoparticles as Multifunctional Immunoadjuvants with Ultrahigh Photosensitizer and Antigen Loading Efficiency for Improved Cancer Photodynamic Immunotherapy
AU - Ding, Binbin
AU - Shao, Shuai
AU - Yu, Chang
AU - Teng, Bo
AU - Wang, Meifang
AU - Cheng, Ziyong
AU - Wong, Ka Leung
AU - Ma, Ping'an
AU - Lin, Jun
N1 - Funding Information:
This project is financially supported by the National Natural Science Foundation of China (Grant Nos. NSFC 51720105015, 51672269, 51332008, 51772124, 21521092, and 51872282), the National Basic Research Program of China (Grant No. 2014CB643803), Science and Technology Development Planning Project of Jilin Province (Grant Nos. 20170101188JC and 20180520163JH), Youth Innovation Promotion Association of CAS (Grant No. 2017273), Overseas, Hong Kong & Macao Scholars Collaborated Researching Fund (Grant No. 21728101), and the CAS-Croucher Funding Scheme for Joint Laboratories (Grant No. CAS18204). All animals in this study were handled according to a protocol approved by the Institutional Animal Care and Use Committee of Jilin University.
PY - 2018/12/27
Y1 - 2018/12/27
N2 - Reported immunoadjuvants still have many limitations, such as inferior cellular uptake capacity and biocompatibility, overly large particle sizes, single function, and unsatisfactory therapeutic efficacy. Here, large-pore mesoporous-silica-coated upconversion nanoparticles (UCMSs) with a size of less than 100 nm are successfully prepared by a typical silica sol–gel reaction using mesitylene as a pore-swelling agent and are applied as a novel immunoadjuvant. The obtained UCMSs not only show significantly higher loadings for the photosensitizers merocyanine 540 (MC540), model proteins (chicken ovalbumin (OVA)), and tumor antigens (tumor cell fragment (TF)), but also are successfully employed for highly efficient in vivo vaccine delivery. The prepared UCMSs–MC540–OVA under 980 nm near-infrared irradiation shows the best synergistic immunopotentiation action, verified by the strongest Th1 and Th2 immune responses and the highest frequency of CD4+, CD8+, and effector-memory T cells. Additionally, nanovaccines UCMSs–MC540–TF can more effectively inhibit tumor growth and increase the survival of colon cancer (CT26)-tumor-bearing BALB/c mice compared with either photodynamic therapy or immunological therapy alone, suggesting the enhanced immunotherapy efficacy and clinical potential of UCMSs as immunoadjuvants for cancer immunotherapy.
AB - Reported immunoadjuvants still have many limitations, such as inferior cellular uptake capacity and biocompatibility, overly large particle sizes, single function, and unsatisfactory therapeutic efficacy. Here, large-pore mesoporous-silica-coated upconversion nanoparticles (UCMSs) with a size of less than 100 nm are successfully prepared by a typical silica sol–gel reaction using mesitylene as a pore-swelling agent and are applied as a novel immunoadjuvant. The obtained UCMSs not only show significantly higher loadings for the photosensitizers merocyanine 540 (MC540), model proteins (chicken ovalbumin (OVA)), and tumor antigens (tumor cell fragment (TF)), but also are successfully employed for highly efficient in vivo vaccine delivery. The prepared UCMSs–MC540–OVA under 980 nm near-infrared irradiation shows the best synergistic immunopotentiation action, verified by the strongest Th1 and Th2 immune responses and the highest frequency of CD4+, CD8+, and effector-memory T cells. Additionally, nanovaccines UCMSs–MC540–TF can more effectively inhibit tumor growth and increase the survival of colon cancer (CT26)-tumor-bearing BALB/c mice compared with either photodynamic therapy or immunological therapy alone, suggesting the enhanced immunotherapy efficacy and clinical potential of UCMSs as immunoadjuvants for cancer immunotherapy.
KW - adjuvants
KW - immunotherapy
KW - large-pore mesoporous silica
KW - photodynamic therapy
KW - upconversion
UR - http://www.scopus.com/inward/record.url?scp=85055943102&partnerID=8YFLogxK
U2 - 10.1002/adma.201802479
DO - 10.1002/adma.201802479
M3 - Journal article
C2 - 30387197
AN - SCOPUS:85055943102
SN - 0935-9648
VL - 30
JO - Advanced Materials
JF - Advanced Materials
IS - 52
M1 - 1802479
ER -