Environment-Responsive Dopamine Nanoplatform for Tumor Synergistic Therapy

Abstract Nanoparticle-based photothermal therapy (PTT) has emerged as a promising approach in tumor treatment due to its high selectivity and low invasiveness. However, the penetration of near-infrared light (NIR) is limited, leading it fails to induce damage to the deep-seated tumor cells within the tumor tissue. Additionally, inefficient uptake of photothermal nanoparticles by tumor cells results in suboptimal outcomes for PTT. Based on the above-mentioned issues, this study utilized the adhesive properties of photothermal material, polydopamine (PDA), which can successfully load the photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) to achieve combined photothermal and chemotherapy treatment (PDA/DOX&ICG), aiming to compensate for the poor penetration of NIR in tumor tissues and the photothermal conversion performance of PDA. For the purpose of extending the blood circulation time of PDA/DOX&ICG nanoparticles, evading clearance by the body immune system and achieving targeted delivery to tumor tissues, a protective envelopment was created using erythrocyte membranes modified with folate acid (FA-EM). After reaching the tumor tissue, the obtained FA-EM@PDA/DOX&ICG nanoparticles can specific bind with folate acid receptors on the surface of tumor cells. This interaction facilitates improved uptake by tumor cells leading to the subsequent release of loaded DOX and ICG in response to the unique tumor microenvironment. DOX penetration ability can effectively compensate the limitation of NIR penetration at the tumor tissue. While ICG, as a typical photosensitizer, significantly enhances the photothermal conversion performance of FA-EM@PDA/DOX&ICG nanoparticles, thereby inducing tumor cells damage. In vitro and in vivo experimental results demonstrated that the coordinated NIR treatment with FA-EM@PDA/DOX&ICG not only effectively inhibits tumor growth but also exhibits superior biocompatibility, effectively mitigating DOX-induced tissue damage.