TY - JOUR
T1 - Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer
AU - Li, Yong
AU - Li, Xiaosong
AU - Doughty, Austin
AU - West, Connor
AU - Wang, Lu
AU - Zhou, Feifan
AU - Nordquist, Robert E.
AU - Chen, Wei R.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - Metastasis is the major cause of cancer-death. Checkpoint inhibition shows great promise as an immunotherapeutic treatment for cancer patients. However, most currently available checkpoint inhibitors have low response rates. To augment the antitumor efficacy of checkpoint inhibitors, such as CTLA-4 antibodies, a single-walled carbon nanotube (SWNT) modified by a novel immunoadjuvant, glycated chitosan (GC), was used for the treatment of metastatic mammary tumors in mice. We treated the primary tumors by intratumoral administration of SWNT-GC, followed with irradiation with a 1064-nm laser to achieve local ablation through photothermal therapy (PTT). The treatment induced a systemic antitumor immunity which inhibited lung metastasis and prolonged the animal survival time of treated. Combining SWNT-GC-laser treatment with anti-CTLA-4 produced synergistic immunomodulatory effects and further extended the survival time of the treated mice. The results showed that the special combination, PTT + SWNT-GC + anti-CTLA, could effectively suppress primary tumors and inhibit metastases, providing a new treatment strategy for metastatic cancers.
AB - Metastasis is the major cause of cancer-death. Checkpoint inhibition shows great promise as an immunotherapeutic treatment for cancer patients. However, most currently available checkpoint inhibitors have low response rates. To augment the antitumor efficacy of checkpoint inhibitors, such as CTLA-4 antibodies, a single-walled carbon nanotube (SWNT) modified by a novel immunoadjuvant, glycated chitosan (GC), was used for the treatment of metastatic mammary tumors in mice. We treated the primary tumors by intratumoral administration of SWNT-GC, followed with irradiation with a 1064-nm laser to achieve local ablation through photothermal therapy (PTT). The treatment induced a systemic antitumor immunity which inhibited lung metastasis and prolonged the animal survival time of treated. Combining SWNT-GC-laser treatment with anti-CTLA-4 produced synergistic immunomodulatory effects and further extended the survival time of the treated mice. The results showed that the special combination, PTT + SWNT-GC + anti-CTLA, could effectively suppress primary tumors and inhibit metastases, providing a new treatment strategy for metastatic cancers.
KW - 1064-nm laser
KW - Breast cancer
KW - Checkpoint inhibition
KW - Glycated chitosan
KW - Immunotherapy
KW - Metastasis
KW - Photothermal therapy
KW - Single-walled carbon nanotube
UR - http://www.scopus.com/inward/record.url?scp=85063401612&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2019.02.009
DO - 10.1016/j.nano.2019.02.009
M3 - Article
C2 - 30844573
AN - SCOPUS:85063401612
SN - 1549-9634
VL - 18
SP - 44
EP - 53
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
ER -