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Prussian blue (PB) has been used as a photothermal conversion agent to generate heat to induce localized damage to tumor. However, its therapeutic efficiency is far from satisfactory. One of the major obstacles is that the maximum NIR absorption peak of PB within 690-720 nm cannot be optimized near the wavelength of the laser to enhance its therapeutic efficiency. Herein, we report that the integration of Gd into PB nanocrystals (GPB NCs) enables PB with tunable localized surface plasmon resonances (LSPRs) from 710 to 910 nm, achieving the maximum NIR peak near the wavelength of the laser. Concurrently, the efficiency of dual-mode imaging including photoacoustic imaging and magnetic resonance imaging has been greatly improved. These enhancements in dual-mode imaging and photothermal therapy enable PB with low nanomaterial dose and laser flux. Additionally, it is found that GPB NCs show the capability of not only acting as a chemical probe with tunable sensitivity but also scavenging reactive oxygen species. The integration of functional ions into a photothermal conversion agent is an efficient strategy to improve the synergy of nanoagent, enchancing tumor theranostic efficiency.

Chemodynamic therapy (CDT) is an emerging field, which utilizes intratumoral iron-mediated Fenton chemistry for cancer therapy. However, the slightly acidic tumor environment is improper for the classical Fenton reaction, which is generally energetic in a narrow pH range (e.g., pH = 3–4). Herein, a kind of ultrasmall bovine serum albumin (BSA)-modified chalcopyrite nanoparticles (BSA-CuFeS2 NPs) was synthesized via a facile aqueous biomineralization strategy, which shows high dispersity and biocompatibility. Interestingly, the obtained BSA-CuFeS2 shows a pH-independent Fenton-like reaction, which could exert Fenton-like activity to efficiently generate •OH under a weak acidic tumor environment. Combined with the extraordinarily high photothermal conversion (38.8%), BSA-CuFeS2 shows the synergistic function of high photothermal therapy (PTT) and enhanced CDT, that is, PTT/CDT. Importantly, such ultrasmall BSA-CuFeS2 NPs measuring around 4.9 nm can be quickly cleared out of the body through kidneys and liver, thus effectively avoiding long-term toxicity and systemic toxicity. Moreover, BSA-CuFeS2 NPs can act as an efficient T 2-weighted magnetic resonance imaging (MRI) contrast agent to guide tumor ablation in vivo. This work offers a universal approach to boost production •OH by a pH-independent Fenton-like reaction strategy and achieves MRI-guided synergistic enhanced photothermal–CDT for highly efficient tumor treatment.

Magnetite (Fe 3 O 4 ) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH−CDT synergistic therapy based only on a single component of Fe 3 O 4 still remains a challenge. Herein, hollow Fe 3 O 4 mesocrystals (MCs) are constructed via a modified solvothermal method. Owing to the distinctive magnetic property of the mesocrystalline structure, Fe 3 O 4 MCs show excellent magnetothermal conversion efficiency with a specific absorption rate of 722 w g −1 at a Fe concentration of 0.6 mg mL −1 , much higher than that of Fe 3 O 4 polycrystals (PCs). Moreover, Fe 3 O 4 MCs also exhibit higher peroxidase-like activity than Fe 3 O 4 PCs, which may be ascribed to the higher ratio of Fe 2+ /Fe 3+ and more oxygen defects in the Fe 3 O 4 MCs. Detailed in vivo results confirm that Fe 3 O 4 MCs can instantly initiate CDT by producing the detrimental • OH, and such boosted reactive oxygen levels not only induces cell apoptosis but also reduces the expression of heat shock proteins, thus enabling low-temperature-mediated MH. More importantly, the in situ rising temperature resulted from MH in turn facilitates CDT, thus achieving a self-augmented synergistic effect between MH and CDT.

Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of •OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.

A pH and magnetic dual-responsive hydrogel highly sensitive to tumor acid microenvironment and efficient responsive magnetic-hyperthermia cancer eradication.

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(1) Background: Acute ischemic stroke (IS) is one of the main causes of human disability and death. Therefore, multifunctional nanosystems that effectively cross the blood–brain barrier (BBB) and efficiently eliminate reactive oxygen species (ROS) are urgently needed for comprehensive neuroprotective effects. (2) Methods: We designed a targeted transferrin (Tf)-based manganese dioxide nanozyme (MnO2@Tf, MT) using a mild biomimetic mineralization method for rebalancing ROS levels. Furthermore, MT can be efficiently loaded with edaravone (Eda), a clinical neuroprotective agent, to obtain the Eda-MnO2@Tf (EMT) nanozyme. (3) Results: The EMT nanozyme not only accumulates in a lesion area and crosses the BBB but also possesses satisfactory biocompatibility and biosafety based on the functional inheritance of Tf. Meanwhile, EMT has intrinsic hydroxyl radical-scavenging ability and superoxide-dismutase-like and catalase-like nanozyme abilities, allowing it to ameliorate ROS-mediated damage and decrease inflammatory factor levels in vivo. Moreover, the released Mn2+ ions in the weak acid environment of the lesion area can be used for magnetic resonance imaging (MRI) to monitor the treatment process. (4) Conclusions: Our study not only paves a way to engineer alternative targeted ROS scavengers for intensive reperfusion-induced injury in ischemic stroke but also provides new insights into the construction of bioinspired Mn-based nanozymes.