Contrast agents (CAs) play a crucial role in high-quality magnetic resonance imaging (MRI) applications. At present, as a result of the Gd-based CAs which are associated with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide nanoparticles, Mn-based CAs which have a good biocompatibility and bright images are considered ideal for MRI. In addition, manganese oxide nanoparticles (MONs, such as MnO, MnO₂, Mn₃O₄, and MnO_x) have attracted attention as T1-weighted magnetic resonance CAs due to the short circulation time of Mn(II) ion chelate and the size-controlled circulation time of colloidal nanoparticles. In this review, recent advances in the use of MONs as MRI contrast agents for tumor detection and diagnosis are reported, as are the advances in in vivo toxicity, distribution and tumor microenvironment-responsive enhanced tumor chemotherapy and radiotherapy as well as photothermal and photodynamic therapies.

Hypoxia is one of the marked features of malignant tumors, which is associated with several adaptation changes in the microenvironment of tumor cells. Therefore, targeting tumor hypoxia is a research hotspot for cancer therapy. In this review, we summarize the developing chemotherapeutic drugs for targeting hypoxia, including quinones, nitroaromatic/nitroimidazole, N-oxides, and transition metal complexes. In addition, redox-responsive bonds, such as nitroimidazole groups, azo-groups, and disulfide bonds, are frequently used in drug delivery systems for targeting the redox environment of tumors. Both hypoxia-activated prodrugs and redox-responsive drug delivery nanocarriers have significant effects on targeting tumor hypoxia for cancer therapy. Hypoxia-activated prodrugs are commonly used in clinical trials with favorable prospects, while redox-responsive nanocarriers are currently at the experimental stage.

Combination chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PCA). However, the pharmacokinetic distinction between the relevant drugs is an insurmountable barrier to the realization of their synergistic use against cancer. To overcome the disadvantages of combination chemotherapy in the treatment of PCA, targeted nanoparticles (NPs), which can codeliver docetaxel (DOC) and doxorubicin (DOX) at optimal synergistic proportions, have been designed. In this study, the DOC and DOX codelivery nanoparticles (DDC NPs) were constructed by hyaluronic acid (HA) and cationic amphipathic starch (CSaSt) through a self-assembly process. Human PCA cell lines (PC-3, DU-145, and LNCap) and mouse models were then used for evaluation in vitro and in vivo, respectively, of delivery and antitumor effects. The DDC NPs were spherical with rough surfaces, and the size and zeta potential were 68.4 ± 7.1 nm and -22.8 ± 2.2 mV, respectively. The encapsulation efficiencies of DOC and DOX in the NPs were 96.1 ± 2.3% and 91.4 ± 3.7%, respectively, while the total drug loading was 9.1 ± 1.7%. Moreover, the ratio of DOC to DOX in the DDC NPs was approximately 1:400, which aligned with the optimal synergistic proportions of the drugs. The DDC NPs exhibited excellent loading capacities, performed sustained and enzymatic release, and were stable in PBS, medium, and serum. After investigations in vitro, the DDC NPs were as effective as the dual drug combination in terms of cytotoxicity, antimigration, and apoptosis. Internalization results indicated that the DDC NPs could effectively deliver and fully release the payloads into PCA cells, and the process was mediated by the ligand-receptor interaction of HA with the CD44 protein. Low toxicity in vivo was confirmed by acute toxicity and hemolytic assays. The distribution in vivo showed that DDC NPs could enhance the accumulation of drugs in tumors and decrease nonspecific accumulation in normal organs. More importantly, DDC NPs significantly promoted the curative effect of the DOC and DOX combination in the PCA cell xenograft mouse model, indicating that the drugs with NPs did indeed act synergistically. This study suggests that the DDC NPs possess noteworthy potential as prospects for the development of PCA clinical chemotherapy.