Biomimetic black phosphorus quantum dots-based photothermal therapy combined with anti-PD-L1 treatment inhibits recurrence and metastasis in triple-negative breast cancer

Abstract

Background Triple-negative breast cancer (TNBC) is a highly aggressive malignant disease with a high rate of recurrence and metastasis, few effective treatment options and poor prognosis. Here, we designed and constructed a combined photothermal immunotherapy strategy based on cancer cell membrane-coated biomimetic black phosphorus quantum dots (BBPQDs) for tumor-targeted photothermal therapy and anti-PD-L1 mediated immunotherapy. Results BBPQDs have good photothermal conversion efficiency and can efficiently target tumor cells through homologous targeting and tumor homing. Under near infrared irradiation, we found that BBPQDs kill tumors directly through photothermal effects and induce dendritic cells maturation. In vivo studies have confirmed that the combined photothermal immunotherapy strategy displays a stronger antitumor activity than anti-PD-L1 monotherapy. In addition, BBPQDs-mediated photothermal therapy in combination with anti-PD-L1 treatment inhibit tumor recurrence and metastasis by reprograming the immunosuppressive tumor microenvironment into an immune-active microenvironment, and promoting the local and systemic antitumor immune response. We further found that the combined photothermal immunotherapy strategy can produce an immune memory effect against tumor rechallenge. Conclusions This study provides a novel therapeutic strategy for inhibiting the recurrence and metastasis of TNBC, with broad application prospects.

Biomimetic doxorubicin/ginsenoside co-loading nanosystem for chemoimmunotherapy of acute myeloid leukemia

“…It is well known that DCs are one of the most powerful antigen presenting cells (APCs) in the immune system [ 30 ]. Chemotherapy is proved to induce ICD, promoting DC maturation [ 31 ]. Mature DCs effectively processes antigens and then presents antigens to T cells, promoting the T cells activation.…”

Potential of Black Phosphorus in Immune‐Based Therapeutic Strategies

“…In recent years, biomembrane-coated nanoparticles, such as red blood cell membranes, cancer cell membranes, platelet membranes, exosomal membranes, and leukocyte membranes, give hope for the successful diagnosis and treatment of tumors [ 46 ]. It was also discovered that the encapsulation of BP into red blood cell membranes and cancer cell membranes, as well as exosomal membranes, not only promoted the blood circulation of BP, but also endowed BP with a targeting ability [ 47 – 49 ]. In addition, scientists also employ other 2D heterostructures, such as hexagonal boron nitride (hBN), graphene, and MoS 2 , to Sandwich BP [ 50 ].…”

“…When combined with anti-PD-1 antibodies, the systems irradiated with NIR inhibited the recurrence and metastasis of a 4T1-luc breast tumor model and B16F10-luc melanoma tumor model. Zhao and colleagues utilized BPQDs coated by homologous targeting of cancer cell membranes to construct a similar nanovaccine [ 102 ]. When combined with anti-PD-L1 antibodies, the nanovaccines also showed the desired tumor immune response in vitro and in vivo [ 102 ].…”

“…Zhao and colleagues utilized BPQDs coated by homologous targeting of cancer cell membranes to construct a similar nanovaccine [ 102 ]. When combined with anti-PD-L1 antibodies, the nanovaccines also showed the desired tumor immune response in vitro and in vivo [ 102 ]. Exosomes, as natural nanoparticles secreted from tumor cells, exhibit a variety of advantages when used as delivery systems, including homologous targeting ability, nontoxicity, excellent biocompatibility, high drug carrying capacity, and low or no immunogenicity [ 103 ].…”

“…For example, Nguyen et al successfully employed BP to deliver PD-L1 inhibitor peptides into HCT-116 and B-16 cells, which significantly inhibited the expression of PD-L1 on tumor cells [ 122 ]. Researchers from different teams demonstrated that when combined with anti-PD-L1 antibodies, PIT benefitting from BPQDs effectively inhibited the growth and metastasis of triple-negative breast cancers by increasing the synergistic immunotherapy effect [ 48 , 102 ]. Compared with PD-1/PD-L1 blockades, CTLA4 inhibitors can significantly inhibit regulatory T cells (Tregs), which promote the immune escape of tumor cells.…”