To study the antitumor efficacy, mice with tumors were randomly
divided into five groups (n = 6) and subjected to different treatments: 1,
PBS; 2, Td@TsG@C; 3, Td@Gox@C; 4, Td@Gox-TsG@C; 5, intravenously
injected with Td@Gox-TsG@C and then intraperitoneally injected with
a-PD-1 (200 µg each time) 12 h later (Td@Gox-TsG@C+aPD1). The
intravenously injected dose was 10 mg kg−1 (according to the amount
of Gox) each time for five times in total. The tumor volumes and body
weights of the mice were measured every other day for 14 days. Blood
biochemical test (ALT, AST, BUN, CR) and H&E staining of the five major
organs (heart, liver, spleen, lung, and kidney) were carried out at 12 h
post-treatment to prove that the body’s immune response resulted in
minimal side effects to major organs. The tumors of mice were harvested
to evaluate the infiltrated CD8+ T cells by immunofluorescence analysis.
ELISA Analysis: Serum cytokine levels were determined by enzyme-
linked immunosorbent assays (ELISAs) using antibody pairs specific to
these cytokines, following protocols recommended by the manufacturer.
Mice with tumors were divided into six groups (n = 6) and subjected to
different treatments: 1, PBS; 2, Td@TsG@C; 3, Td@Gox@C; 4, Td@Gox-
TsG@C; 5, Td@Gox-TsG@C+aPD1. After 12 h, the mice were sacrificed
to harvest serum. Serum levels of IL-6 and TNF-α were determined with
the Mouse IL-6 ELISA Kit and TNF-α Mini ELISA Kit, respectively.
Statistical Analysis: All values in the present study were expressed
as means SD. The significance between two groups was analyzed by
a two-tailed Student t-test. p-value of less than 0.05 was considered
significant (***p < 0.001, **p < 0.01, *p < 0.05).
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Supporting Information
Supporting Information is available from the Wiley Online Library or
from the author.
Acknowledgements
This work was supported by Key Research and Development Program
of Shandong Province (2018YFJH0502), National Natural Science
Foundation of China (91753111, 21927881, 21874086, and 21775094),
National Key R&D Program of China (2019YFA0210100), and Youth
Innovation Science and Technology Program of Higher Education
Institution of Shandong Province (2019KJC022). Animal experiments
were reviewed and approved by the Ethics Committee of Shandong
Normal University, Jinan, P. R. China (approval number AEECSDNU
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The authors declare no conflict of interest.
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Keywords
calreticulin proteins, DNA tetrahedron, endoplasmic reticulum stress,
immunotherapies, nanoregulators
Received: January 19, 2020
Revised: August 24, 2020
Published online:
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