Although polymeric platinum(IV) (Pt(IV)) prodrugs can reduce the side effects of cisplatin, the efficacy of the prodrug is still limited by its non-targeted distribution, poor penetration in deep tumor tissue, and low cytotoxicity in tumor cells. To improve the clinical potential of polymeric prodrug micelle, we synthesized amphiphilic polymeric Pt(IV) with high Pt content (22.5%), then developed a theranostic nanocomplex by integrating polymeric Pt(IV) with superparamagnetic Mn_0.6Zn_0.4Fe₂O₄ via simple self-assembly. Due to the high content of Mn_0.6Zn_0.4Fe₂O₄ (41.7% w/w), the theranostic nanocomplex showed high saturation magnetization (103.1 emu g⁻¹) and excellent magnetocaloric effect (404 W g⁻¹), both of them indicating its advantages in efficient magnetic targeting (MT), magnetic hyperthermia (MH), and magnetic resonance imaging (MRI). In vitro, in combination with MH, the theranostic nanocomplex showed as high cytotoxicity as cisplatin because of a significant increase in platinum of cellular uptake. In vivo, the accumulation of theranostic nanocomplex in tumors was increased by MT and confirmed by MRI. Furthermore, MH improved penetration of theranostic nanocomplex in tumors as expanding blackened area in tumors was observed by MRI. Based on these properties, the theranostic nanocomplex, under the assistance of MT and MH, showed the highest tumor growth inhibition rate (88.38%) after different treatments, while the body weight of mice increased slightly, indicating low side effects compared to those of cisplatin. The study provided an advanced theranostic nanocomplex with low toxicity and high efficacy, indicating a great clinical potential of polymeric Pt(IV).

We prepared a tumor microenvironment-responsive magnetic nanofluid (MNF) for improving tumor targeting, imaging and treatment simultaneously. For this purpose, we synthesized sulfonamide-based amphiphilic copolymers with a suitable pK_a at 7.0; then, we utilized them to prepare the tumor microenvironment-responsive MNF by self-assembly of the sulfonamide-based amphiphilic copolymers and hydrophobic monodispersed Fe₃O₄ nanoparticles at approximately 8 nm. After a series of characterizations, the MNF showed excellent application potential due to the fact of its high stability under physiological conditions and its hypersensitivity toward tumor stroma by forming aggregations within neutral or weak acidic environments. Due to the fact of its tumor microenvironment-responsiveness, the MNF showed great potential for accumulation in tumors, which could enhance MNF-mediated magnetic resonance imaging (MRI), magnetic hyperthermia (MH) and Fenton reaction (FR) in tumor. Moreover, in vitro cell experiment did not only show high biocompatibility of tumor microenvironment-responsive MNF in physiological environment, but also exhibit high efficacy on inhibiting cell proliferation by MH-dependent chemodynamic therapy (CDT), because CDT was triggered and promoted efficiently by MH with increasing strength of alternating magnetic field. Although the current research is limited to in vitro study, these positive results still suggest the great potential of the MNF on effective targeting, diagnosis, and therapy of tumor.