Environment-responsive polydopamine nanoparticle cross-linked phenylboronic-grafted hyaluronic acid with enzyme-like properties for tumor synergistic therapy

Abstract

Solid tumors are usually surrounded by a dense extracellular matrix, which increases the rigidity and stress of tumors, resulting in reduced perfusion of antitumor drugs. Tumor cell reprogramming during tumor growth makes them prone to drug resistance in tumor treatment. In this study, we developed a photosensitive gel system (NS/FPDA@DOX HA) with enzyme-like properties for tumor synergistic therapy. This system was fabricated via the reaction of folate-modified and doxorubicin-loaded polydopamine nanoparticles with phenylboronic-grafted hyaluronic acid to load nattokinase. After intratumoral injection and exposure under near-infrared light, NS/FPDA@DOX HA converts light energy into heat energy triggering tumor cell death and releasing tumor-associated antigens that can boost body antitumor immunity. Subsequently, nattokinase was gradually released by ROS/GSH/pH-triggered NS/FPDA@DOX HA degradation, which could dissolve the protective shell of fibrin surrounding the tumor tissues. Besides, the released FA-P&PDA@DOX NAs utilize their surface folate molecules to specifically bind with folate receptors on the surface of tumor cells to enhance their uptake by tumor cells. Then, the acidic lysosome can achieve the precise release of DOX. In summary, NS/FPDA@DOX HA can utilize nattokinase to promote the infiltration of drug molecules and immune cells into solid tumor tissues, which when combined with photothermal therapy can effectively inhibit tumor recurrence and metastasis.