Calcium-carbonate packaging magnetic polydopamine nanoparticles loaded with indocyanine green for near-infrared induced photothermal/photodynamic therapy

Indocyanine green (ICG) is an efficient photosensitizer that can facilitate producing cytotoxic reactive oxygen species (ROS). At the same time, ICG also has characteristic absorption of near-infrared light and thus can induce a strong photothermal effect. Both of these important features of ICG may be applied for noninvasive light-induced tumor ablation. On the other hand, ICG is lack of stability in blood circulation and susceptible to aggregation or premature clearance from the body. These issues need to be effectively addressed before antitumor application of ICG becomes possible. Herein, a nanocomposite consisting of calcium carbonate modified magnetic polydopamine (PDA) nanoparticles and loaded with ICG, namely Fe3O4@PDA@CaCO3/ICG (FPCI) NPs, was developed to integrate the photothermal capability of PDA with the photodynamic capability of ICG. Particularly, calcium carbonate not only entrapped ICG in the form of stable aggregate to evade blood clearance, but also facilitated controlled release of ICG in response to acidic tumor microenvironment via self-decomposition. With the aid of magnetic guidance, this multifunctional therapeutic agent makes it possible to achieve the combination of photothermal (PTT) and photodynamic therapies (PDT) against tumors, which was demonstrated by this proof-of-concept study based on in vitro and in vivo tumor models. STATEMENT OF SIGNIFICANCE: Currently, there is an ongoing trend of realizing precise and targeted tumor therapy using functional nanocomplexes. Magnetic particles, which can be manipulated by a magnetic field, have attracted increasing attention for tumor therapy. This submitted work demonstrated that calcium carbonate nanoshell was precipitated onto magnetic nanocores mediated by polydopamine. Moreover, indocyanine green (ICG), as a potent photosensitizer, was embedded in this nanocomplex and protected by the calcium carbonate nanoshell, resulting in high drug loading efficiency and enhanced drug stability on the carrier. This new nanocomposite was demonstrated to achieve controlled and pH-responsive release of ICG in tumor environment. This work explored the relationship between the physiochemical properties of the nanocomplex and their potential biomedical applications, aiming to inspire the development of analogous nanoplatforms featured with calcium carbonate blocks.