The low response rate and serious side effects of cancer
treatment
pose significant limitations in immunotherapy. Here, we developed
a multifunctional tetrahedral DNA framework (TDF) as a drug carrier
to recruit chemotherapeutants and trigger immunogenic cell death (ICD)
effects, which could turn tumors from cold to hot to boost the efficacy
of antitumor immunotherapy. A tumor-targeting peptide RGD was modified
on the TDF to increase the delivery efficiency, and the chemotherapeutant
doxorubicin (DOX) was loaded to induce ICD effects, which were assisted
by the immune adjuvant of CpG immunologic sequences linked on TDF.
We demonstrated that the multifunctional TDF could suppress 4T1 breast
tumor growth by increasing tumor infiltration of CD8+ T
cells, upregulating granzyme B and perforin expressions to twice as
much as the control group, and decreasing 30% CD25+ Treg
cells. Furthermore, the combination of α-PD-1 could inhibit
the growth of distant tumor and suppressed tumor recurrence in a bilateral
syngeneic 4T1 mouse model; the distant tumor weight inhibition rate
was about 91.6%. Hence, through quantitatively targeting the delivery
of DOX to reduce the side effects of chemotherapy and sensitizing
the immune response by ICD effects, this multifunctional TDF therapeutic
strategy displayed better treatment effect and a promising clinical
application prospect.