to perform PDT. [7] PSs absorb laser energy in the presence of O 2 to produce cytotoxic reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) that causes the destruction of the genetic material in cancer cells, leading to cell apoptosis, or necrosis. [7][8][9][10] The O 2 involved in PDT improves tumor destruction and reduces the toxic side effects as compared with other conventional therapeutic modalities like radiotherapy, chemotherapy, and surgery. [11][12][13][14][15] However, hypoxia, one of the hallmarks of malignant tumors, [16][17][18] induces an unexpected resistance of tumors to PDT, since molecular O 2 plays an essential role during the process. Some types of nanocatalysts have been used to address this dilemma, such as manganese dioxide (MnO 2 ) nanoparticles, carbon dot, and single-atom ruthenium (Ru) for an in situ catalysis of the decomposition of H 2 O 2 to generate O 2 . [6,14,19] This could be an effective strategy to relieve hypoxia in the tumor microenvironment (TME), thus becoming a potential approach to improve the efficacy of PDT. [20] Additionally, the acidic TME with an excessive amount of H 2 O 2 is a natural activator of these nanocatalysts, making them intelligent nanocatalysts for tumor specific therapy. [21][22][23] Recently, MnO 2 nanostructures have received extensive attention in the field of bio-applications for their efficient O 2 production and easy synthesis, [24][25][26][27] enhancing the effect of radiation therapy, [27] chemotherapy, [28] and PDT. [29] In addition, MnO 2 is rapidly decomposed into water soluble Mn 2+ ion in an acidic condition, [6,[30][31][32][33][34] and excreted through the bile into the feces, avoiding unexpected accumulation and long-term toxicity in vivo. [6,29] However, MnO 2 nanostructures without surface coating have a poor structure stability under physiological conditions, [35] and it is difficult to control their size and morphology during the synthesis, thus, increasing the uncertainty of the reactivity of the nanomaterial. [25] Therefore, it is highly desirable to construct MnO 2 nanoparticles with uniform morphology, high stability and biocompatibility for biomedical applications.Ferritin (Ftn) is an endogenous iron storage protein composed of 24 subunits, with a hollow structure of 12 nm in the external diameter and an inner cavity of 8 nm. [36] Ftn has been widely used as a superior protein nanocage for the Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O 2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO 2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/ Ftn@MnO 2 ) for tumor therapy. Ce6/Ftn@MnO 2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis dem...

In spite of the successful use of monoclonal antibodies (mAbs) in clinic for tumor treatment, their applications are still hampered in therapeutic development due to limitations, such as tumor penetration and high cost of manufacture. Nanobody, a single domain antibody that holds the strong antigen targeting and binding capacity, has demonstrated various advantages relative to antibody. Nanobody is considered as a next‐generation of antibody‐derived tool in the antigen related recognition and modulation. A number of nanobodies have been developed and evaluated in different stages of clinical trials for cancer treatment. Here we summarized the current progress of nanobody in tumor diagnosis and therapeutics, particularly on the conjugation of nanobody with functional moieties. The nanobody conjugation of diagnostic agents, such as radionuclide and optical tracers, can achieve specific tumor imaging. The nanobody‐drug conjugates can enhance the therapeutic efficacy of anti‐tumor drugs and reduce the adverse effects. The decoration of nanobody on nanodrug delivery systems can further improve the drug targeting to specific tumors. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Nanocatalysts, a class of nanomaterials with intrinsic enzyme‐like activities, have been widely investigated for cancer catalytic therapy in recent years. However, precise construction of nanocatalysts with excellent enzyme catalytic activity and biosafety for tumor therapy still remains challenging. Here, a biodegradable nanocatalyst, PEGylated CuxMnySz (PCMS), is reported that can promote cascade catalytic reactions in tumor microenvironment (TME) while confining off‐target side effects on normal tissues. PCMS not only catalyzes the cascade conversion of endogenous hydrogen peroxide (H2O2) to oxygen (O2) via catalase‐like activity and then to superoxide radical (·O2−) via oxidase‐like activity in the TME, but also effectively depletes intracellular glutathione via glutathione oxidase‐like activity. The cascade catalytic reactions, by taking advantage of high H2O2 level in tumor cells, result in an enhanced enzyme catalytic effect in generation of ·O2−. More importantly, PCMS exhibits prominent photothermal effect under NIR‐II 1064 nm laser irradiation that can further enhance chemodynamic therapy (CDT) efficacy in tumors. In addition, the biodegradation in TME and excellent photothermal effect of PCMS are beneficial to magnetic resonance imaging, photoacoustic imaging and infrared thermal imaging, resulting in tracing the fate of PCMS in vivo. This study provides a new tool for rational design of TME‐responsive nanocatalysts with high biocompatibility for tumor catalytic therapy.

Nanocatalysts are promising tumor therapeutics due to their ability to induce reactive oxygen species in the tumor microenvironment. Although increasing metal loading can improve catalytic activity, the quandary of high metal content versus potential systemic biotoxicity remains challenging. Here, a fully exposed active site strategy by site‐specific anchoring of single iridium (Ir) atoms on the outer surface of a nitrogen‐doped carbon composite (Ir single‐atom catalyst (SAC)) is reported to achieve remarkable catalytic performance at ultralow metal content (≈0.11%). The Ir SAC exhibits prominent dual enzymatic activities to mimic peroxidase and glutathione peroxidase, which catalyzes the conversion of endogenous H2O2 into •OH in the acidic TME and depletes glutathione (GSH) simultaneously. With an advanced support of GSH‐trapping platinum(IV) and encapsulation with a red‐blood‐cell membrane, this nanocatalytic agent (Pt@IrSAC/RBC) causes intense lipid peroxidation that boosts tumor cell ferroptosis. The Pt@IrSAC/RBC demonstrates superior therapeutic efficacy in a mouse triple‐negative mammary carcinoma model, resulting in complete tumor ablation in a single treatment session with negligible side effects. These outcomes may provide valuable insights into the design of nanocatalysts with high performance and biosafety for biomedical applications.

Pt IV prodrugs can overcome resistance and side effects of conventional Pt II anticancer therapies.B y 19 F-labeling of aP t IV prodrug (Pt-FBA, FBA = p-fluorobenzoate), the activation under physiological conditions could be investigated. Unlike single-electron reductants,multi-electron agents can efficiently promote the two electrons reduction of Pt IV to Pt II . The activation of Pt-FBAi nc ell lysate is highly dependent upon the type of cancer cells.When administered to E. coli, Pt-FBAisreduced intracellularly and free FBAcan shuttle out of the cell. The reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of Zn II ions.W hen injected into mice,P t-FBAu ndergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless,u nreduced Pt-FBAc an accumulate to detectable levels in liver and kidneys.T he 19 FNMR approach has the advantage of avoiding the interference of all background signals.Scheme 1. Chemical structures of cisplatin, oxoplatin, satraplatin,a nd Pt-FBA.