Metal-organic framework-mediated multifunctional nanoparticles for combined chemo-photothermal therapy and enhanced immunotherapy against colorectal cancer

Abstract

Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.

Keywords: Combination therapy; Immune checkpoint blockade; Immunogenic cell death; Metal-organic framework; Photothermal therapy.