Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative "cold" triple-negative breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36733927.
- Also identified by DOI 10.1016/j.bioactmat.2023.01.014 and PMC identifier 9879764.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Triple-negative breast cancer (TNBC) due to lack of clear target and notorious "cold" tumor microenvironment (TME) is one of the most intractable and lethal malignancies. Tuning "cold" TME into "hot" becomes an emerging therapeutic strategy to TNBC. Herewith, we report that integrin-targeting micellar gemcitabine and paclitaxel (ATN-mG/P, ATN sequence: Ac-PhScNK-NH<sub>2</sub>) cooperating with polymersomal CpG (NanoCpG) effectively "heated up" and treated TNBC. ATN-mG/P exhibited greatly boosted apoptotic activity in 4T1 cells, induced potent immunogenic cell death (ICD), and efficiently stimulated maturation of bone marrow-derived dendritic cells (BMDCs). Remarkably, in a postoperative TNBC model, ATN-mG/P combining with NanoCpG promoted strong anti-cancer immune responses, showing a greatly augmented proportion of mature DCs and CD8<sup>+</sup> T cells while reduced immune-suppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T<sub>reg</sub>), which led to complete inhibition of lung metastasis and 60% mice tumor-free. The co-delivery of gemcitabine and paclitaxel at desired ratio in combination with NanoCpG provides a unique platform for potent chemoimmunotherapy of "cold" tumors like TNBC.