Microfluidic synthesis of fibronectin-coated polydopamine nanocomplexes for self-supplementing tumor microenvironment regulation and MR imaging-guided chemo-chemodynamic-immune therapy

ABSTRACT: Development of nanomedicines to overcome the hindrances of tumor microenvironment (TME) for tumor theranostics with alleviated side effects remains challenging. We report here a microfluidic synthesis of artesunate (ART)-loaded polydopamine (PDA)/iron (Fe) nanocomplexes (NCs) coated with fibronectin (FN). The created multifunctional Fe-PDA@ART/FN NCs (FDRF NCs) with a mean size of 161.0 ​nm exhibit desired colloidal stability, monodispersity, r1 relaxivity (4.96 ​mM−1s−1), and biocompatibility. The co-delivery of the Fe2+ and ART enables enhanced chemodynamic therapy (CDT) through improved intracellular reactive oxygen species generation via a cycling reaction between Fe3+ and Fe2+ caused by the Fe3+-mediated glutathione oxidation and Fe2+-mediated ART reduction/Fenton reaction for self-supplementing TME regulation. Likewise, the combination of ART-mediated chemotherapy and the Fe2+/ART-regulated enhanced CDT enables noticeable immunogenic cell death, which can be collaborated with antibody-mediated immune checkpoint blockade to exert immunotherapy having significant antitumor immunity. The combined therapy improves the efficacy of primary tumor therapy and tumor metastasis inhibition by virtue of FN-mediated specific targeting of FDRF NCs to tumors with highly expressed αvβ3 integrin and can be guided through the Fe(III)-rendered magnetic resonance (MR) imaging. The developed FDRF NCs may be regarded as an advanced nanomedicine formulation for chemo-chemodynamic-immune therapy of different tumor types under MR imaging guidance. Graphical abstract Image 1 Highlights • Intelligent Fe-PDA@ART/FN NCs can be prepared via microfluidics.• FDRF NCs have dual-pathway enhanced ROS generation ability.• Sustained TME regulation is achieved via a cycling reaction between Fe3+ and Fe2+.• Combined therapy-induced ICD can significantly activate antitumor immune response.• FDRF NCs enable MR imaging and ICB-integrated tri-mode tumor therapy.

SUBMITTER: Yang R 

PROVIDER: S-EPMC10220494 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature