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RNA interference (RNAi), which can inhibit the expression or transcription of specific genes, is considered to be a revolutionary tool for mediating gene therapy. Small interfering RNA (siRNA) is an important therapeutic agent for RNAi. However, the clinical application of siRNA‐based gene silencing is still limited due to the easy degradation of siRNA during the circulation in the body and the difficulty in delivering siRNA to desired tissues and cells. The rapid development of nanotechnology provides new ideas for siRNA delivery and a large variety of nanocarriers have been designed to solve the problems of siRNA delivery including easy degradation, lack of targeting ability, poor internalization ability, easy to cause induction of immune response and so on. Here, this review introduces the mechanism of RNAi in gene therapy, then summarizes the developments on nanocarriers for siRNA delivery, and specially focuses on the functional modification strategies of nanocarriers to construct multifunctional siRNA delivery vectors. Lastly, the future development and challenges of siRNA delivery vector are discussed, along with the current application of siRNA in tumor treatment clinical trials. It is hoped that this review can provide useful information to help transform siRNA‐mediated gene therapy into clinical application. [ABSTRACT FROM AUTHOR]

Herein, a multi-functional nanoplatform (PDA-DTC/Cu–MnO2) was established, which has been employed for MR imaging-guided multi-therapy (CDT, PTT and chemotherapy) for cancer treatment. The in vitro and in vivo results confirmed that the biocompatible nanoplatform could significantly induce tumor cell death and inhibit tumor growth. [ABSTRACT FROM AUTHOR]

Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu9S5@mSiO2-PpIX@MnO2@CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors. CpG oligonucleotides can stimulate an anticancer immune response. Zhou et al. now develop nanoparticles that can deliver CpG, which promotes cancer cell death after photothermal and photodynamic therapy in vitro and in vivo, concomitant with an immunological response. [ABSTRACT FROM AUTHOR]

Despite drug delivery nanoplatforms receiving extensive attention, development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. Herein, a versatile nanoplatform based on a zirconium framework (UiO‐66‐N3) was synthesized, which demonstrated a combined photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy (CT) for cancer treatment. A RuII polypyridyl alkyne complex (Ra) as a photosensitizer was modified into a nanoplatform by click reactions for the first time. When exposed to suitable light irradiation, the as‐prepared multifunctional nanoplatform (UiO‐Ra‐DOX‐CuS) not only demonstrated efficient 1O2 generation, but also exhibited excellent photothermal conversion ability. In particular, the nanotherapeutic agent presented a dual‐stimuli response; either acidic environment or NIR laser irradiation would trigger the drug release. The synergetic efficacy of UiO‐Ra‐DOX‐CuS combined PDT, PTT, and CT, which was evaluated by cell experiments. Moreover, the design could promote the development of RuII polypyridyl alkyne complexes based multifunctional nanoparticles and multimodal cancer treatment. [ABSTRACT FROM AUTHOR]

• Copper-related agents for cancer therapy are overviewed. • Copper depletion for the inhibition of tumor proliferation are summarized. • A series of copper suppliers for tumor removal are reviewed. • Challenges and developments of Cu-related anticancer agents are discussed. As an indispensable micronutrient, copper (Cu) plays an important role in promoting metabolism and maintaining various basic biological functions. Copper homeostasis in the human body is tightly regulated and the imbalance of copper levels can lead to metabolic abnormalities and toxic effects on cells. Hence, Cu-related agents have sparked tremendous attention in the field of cancer therapy. Two copper-related strategies have been proposed for the treatment of tumors: depleting copper inside tumors to inhibit proliferation, and providing excess copper to promote cell apoptosis or cuproptosis. Correspondingly, copper depletors are adopted to reduce copper bioavailability, and a variety of copper-based agents, including copper-based nanosystems, copper complexes and nano-copper complexes, are applied to supplement copper. This review systematically summarizes the recent development of Cu-related agents for cancer therapies from the perspective of copper depletion and copper supplementation. Considering the large number of agents used to supply copper, copper-based nanosystems, copper complexes and nano-copper complexes are discussed in separate sections. Finally, the challenges and the future developments of Cu-related anticancer agents are explored to provide some enlightenment for future research. [ABSTRACT FROM AUTHOR]

The therapeutic application of chemodynamic therapy (CDT) is severely limited by the insufficient intracellular H 2 O 2 and acidity in tumor. Herein, an acid-sensitive nanoplatform (ZIF67-ICG/TAM@GOx) to promote H 2 O 2 and acidity enhancement through intracellular cyclic amplification for enhanced CDT is rationally designed. Notably, the acidic conditions of the tumor microenvironment (TME) can turn on the switch of the nanoplatform, setting free the loaded tamoxifen (TAM) and indocyanine green (ICG). The mitochondrial respiration inhibitor TAM and the superoxide dismutase-mimicking ZIF67 synergistically lead to an increase in the content of O 2 and H 2 O 2 , accelerating the depletion of β- d -glucose by GOx to generate gluconate and H 2 O 2. The gluconate in turn boosts the acidity to facilitate the collapse of nanoparticles, further significantly promoting the accumulation of intracellular H 2 O 2 through a positive circulation. Consequently, the amplificated endogenous H 2 O 2 is catalyzed by Co2+ to liberate hydroxyl radicals (•OH). Besides, ICG-mediated photothermal therapy (PTT) and GOx-induced starvation therapy along with CDT realize the synergistic cancer treatment. Importantly, in vitro and in vivo experiments verified that the nanoplatform performed superior specificity and excellent therapeutic responses. The smart nanoplatform overcomes H 2 O 2 and acidity deficiency simultaneously for intensive CDT, providing new prospects for the development of biocompatible cancer synergistic therapy strategies. In the tumor microenvironment, the released TAM, GOx and ZIF67 synergistically lead to a positive circulation for self-amplified CDT, cooperating with PTT and starvation to realize the synergistic cancer treatment. [Display omitted] • An acidic sensitive nanoplatform (ZIF67-ICG/TAM@GOx) is constructed for specific tumor therapy. • The combination of TAM, ZIF67 and GOx enabled positive circulation to accumulate H 2 O 2 and acidity for boosting CDT. • The disruption of H 2 O 2 homeostasis made the approach of "expanding source and cost-saving" for the increase of H 2 O 2. • The self-amplified CDT along with PTT, GOx-induced starvation realized a novel synergistic cancer therapy strategy. [ABSTRACT FROM AUTHOR]

As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H 2 O 2 /GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC. [Display omitted] • Zal@HM-PTBC was designed to facilitate ferroptosis by triple-enhanced LPO accumulation strategy. • TME induced the collapse of Zal@HM-PTBC and triggered the production of O 2 /ROS , which synergistically amplify LPO level. • The degradation of Zal@HM-PTBC consumed GSH in TME and attenuated "detoxification effect" on LPO by inactivating of GPX4. • The release of zalcitabine effectively led to autophagy dependent LPO accumulation. [ABSTRACT FROM AUTHOR]