4.8 Article

Multifunctional biomimetic nanoplatform based on photodynamic therapy and DNA repair intervention for the synergistic treatment of breast cancer

Journal

ACTA BIOMATERIALIA
Volume 157, Issue -, Pages 551-565

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2022.12.010

Keywords

Immunotherapy; Photodynamic therapy; cGAS-STING pathway; Olaparib; ? H2AX

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This study developed a multifunctional biomimetic nanoplatform for tumor treatment. It can deliver photosensitizer and drug to prevent DNA repair, and activate the immune response through the cGAS-STING pathway, inducing systemic anti-tumor immunity.
Photodynamic therapy (PDT) is a minimally invasive and locally effective treatment method, which has been used in the clinical treatment of a variety of superficial tumors. In recent years, PDT has received extensive attention due to its induction of immunogenic cell death (ICD). However, the repair mechanism of tumor cells and low immune response limit the further development of PDT. To this end, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) is developed to co-deliver the photosensitizer Chlorin e6 (Ce6) and Olaparib (Ola) with the function of preventing DNA repair. The nanoplatform shows efficient tumor targeting and cellular internalization properties due to cell membrane camouflage, and Ce6 and Ola produce a significant synergistic anti-tumor effect under laser irradiation. Meanwhile, the nanoplatform can also activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-interferon gene stimulator signaling (cGAS-STING) pathway to produce cytokines. The damage-associated molecular patterns induced by ICD can work with these cytokines to recruit and stimulate the maturation of dendritic cells and induce the systemic anti-tumor immune response. Overall, this multifunctional biomimetic nanoplatform integrating PDT, chemotherapy, and immunotherapy is highlighted here to boost anti-tumor therapy.

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