Programing Immunogenic Cell Death in Breast Tumors with Designer DNA Frameworks

Abstract

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.

DNA as highly biocompatible carriers for drug delivery

“…These aptamers show great potential as essential components for constructing functional DNA nanoassemblies. Table 1 6–32 presents some aptamers that have been successfully used in DNA-based drug carriers, including AS1411, Sgc8, MUC1, HER-2, and others.…”

Antitumoral and Immunogenic Capacity of β-D-Glucose—Reduced Silver Nanoparticles in Breast Cancer

“…For these, is necessary to develop a better innovative immunotherapy that prolongs patients' survival. [6]; to resolve this problem, various strategies have been developed to induce immunogenic cell death (ICD), an example of this is the use of chemotherapy treatments, such as doxorubicin, that has been demonstrated to be efficient in preclinical studies [7]. Leaving a research gap yet to be proven in a clinical stage.…”