Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

Abstract

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for cancer therapy. In this study, we designed a carrier-free chemophotodynamic nanoplatform (A-C/NPs) using a co-assembly strategy with cytarabine (Ara-C) and chlorin e6 (Ce6) to induce pyroptosis and a subsequent immune response against breast cancer. Mechanistically, A-C/NPs can trigger GSDMEmediated pyroptosis in a controllable manner through reactive oxygen species (ROS) accumulation, causing immunogenic cell death (ICD), in which dying cells release high-mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and calcitonin (CRT). Additionally, Ara-C can stimulate the maturation of cytotoxic T lymphocytes to act synergistically with Ce6-mediated immunogenic cell death (ICD), collectively augmenting the anticancer effect of A-C/NPs. The A-C/NPs showed excellent suppressive effects on the growth of orthotopic, abscopal, and recurrent tumors in a breast cancer mouse model. The chemo-photodynamic therapy (PDT) using the proposed nanomedicine strategy could be a novel strategy for triggering pyroptosis and improving the global anticancer immune response.

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

“…For example, gut microbiota-originated metabolic toxins, such as LPS, can act as PAMPs to activate immune cells [ 123 , 124 ]. In parallel, drug-, smoking-, and circadian rhythm-induced oxidative stress can damage intestinal epithelial cells (IECs), such as Paneth cells and goblet cells, releasing cell debris, calreticulin, heat shock proteins (HSPs) and ATP, which can act as DAMPs to promote the progression of inflammation and subsequent pyroptosis and necroptosis [ 125 , 126 , 127 , 128 ]. Immune cells secrete products that are actively involved in the initiation and preservation of inflammation, leading to gut tissue damage.…”

Photothermal‐Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction

“…Tumor regrowth is the main cause of low clinical efficacy and cancer death, and thus, we investigated the influence of IGC/NPs on inhibiting tumor regrowth. A recurrence model of BALB/c mice with CT26 tumor was established by surgery when the tumor reached a volume of 100 mm 3[ 26,27 ] (Figure 5H,I). The drug was given every other day from the 15 th day to 30 th day after surgery.…”

Nanomedicine-based modulation of redox status for cancer therapy

“…On the other hand, recent research indicates that oxidative damage induction and programmed cell death can also be useful cancer treatment methods. [50] A significant amount of data has demonstrated that development of nanoparticle-based therapy holds huge potential to modulate redox homeostasis for cancer therapy (Fig. 2).…”