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[Display omitted] • The switch for treatment was only triggered under high heat conditions, allowing for human-controlled, on-demand treatment. • CaO 2 degraded in acidic TME, producing H 2 O 2 , O 2 and Ca(OH) 2 , which could improve and remodel TME. • Free Ca2+ accumulated in tumor cells and could initiate the process of calcium overload and calcification. • Calcification could play a role in inhibiting tumor growth and aiding CT imaging. The tumor microenvironment (TME) is complex in composition and unique in nature, and is closely related to the growth, invasion and metastasis of tumor cells. Improving and remodeling the TME to return it to a normalized state can fundamentally disrupt the environment and/or nutrient supply on which tumor cells depend. To achieve this goal, based on the unique physicochemical properties and biological effects of CaO 2 , we designed and constructed a Ca2+ nanogenerator (named as CaO 2 -Cu/ICG@PCM) that enables H 2 O 2 /O 2 self-supplementation and GSH depletion. The 808 nm laser induces the heat generation of photosensitizer indocyanine green (ICG) to initiate a series of reactions, followed by the production of copper ions, H 2 O 2 , O 2 and large amounts of Ca2+, which can eventually lead to the combined treatment of photodynamic therapy (PDT), chemodynamic therapy (CDT) and calcium overload. Additionally, the reaction process is accompanied by the generation of Ca(OH) 2 , which greatly improves the acidic environment of TME and effectively promotes the oxidation process of GSH by H 2 O 2 , achieving the purpose of remodeling TME. It is worth mentioning that a large amount of free Ca2+ accumulating in tumor cells can rapidly initiate the process of calcium overload and calcification, which can not only play a role in tumor suppression, but also assist CT imaging to detect the effect of treatment. Thus, CaO 2 -Cu/ICG@PCM could be a promising candidate for bioimaging and tumor therapy. [ABSTRACT FROM AUTHOR]

The original version of this Article contained an error in the spelling of the author Luke Martinson, which was incorrectly given as Luke Martison. These authors contributed equally: Min Zhang, Jin-Li Luo, Qianqian Sun, James Harber, Alan G. Dawson. [Extracted from the article]

• Honeycomb MnO 2 with catalase-like activity can produce O 2 inside solid tumors. • The HA coating endowed the MCIH with the ability of actively targeted to the tumor site. • CuS nanoparticles and ICG molecules were loaded on with high loading rate (66.8% and 80.22%, respectively). • The released ICG and Mn2+ could be used for fluorescent imaging and T 1 -weighted MR imaging. The tumor microenvironment (TME) is the internal environment where tumor cells grow and develop. Constructing TME-activatable, specific imaging and treatment system is highly desired for accurate cancer diagnosis and therapy. Herein, by utilizing the degrading ability of honeycomb MnO 2 in the TME, a tumor-targeted and O 2 -evolving photothermal/photodynamic therapeutic nanoplatform with dual-modal imaging capability was designed and fabricated. In the structure, self-assembled MnO 2 was regarded as a carrier for cargo loading and O 2 production, and subsequently the CuS nanoparticles (NPs) and indocyanine green (ICG) molecules with ultra- high loading characteristics (CuS NPs could be loaded up to nearly 66.8% and ICG molecules could be loaded up to 80.22%) were loaded and further wrapped in hyaluronic acid (HA), endowing the system with the capability for specific interaction with CD44 over-expressed on tumor cells. Upon irradiation with 808 nm laser, the photothermal therapy (PTT) effects of the CuS NPs and ICG molecules would be triggered with satisfactory photostability. The degradation of the carrier could generate O 2 , thus solving the problem of hypoxia in the TME. Simultaneously, the released ICG molecules could also exert strong photodynamic therapy (PDT) effects when activated by the same light. Indeed, PTT and PDT are two kinds of light-mediated treatment. Moreover, the recovered fluorescence of the ICG molecules and the released Mn2+ resulted in excellent fluorescent imaging and T 1 -weighted MR imaging. An imaging directed synergistic phototherapy has thereby been realized. [ABSTRACT FROM AUTHOR]

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d -α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart "switch" and tumor-targeted "guider", had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency. Image 1 [ABSTRACT FROM AUTHOR]

The current conventional photo-therapeutic agents often show low therapy efficacy because of their single treatment model, the limited penetration depth of excitation light and hypoxia in the tumor microenvironment (TME). Herein, a new type of phthalocyanine manganese (MnPcE 4) photosensitizer with strong NIR absorption was designed and fabricated for the first time, and was used to modify pure Bi nanomaterials to obtain an intelligent multifunctional Bi/MnPcE 4 nanocomposites. The Mn2+ in the Bi/MnPcE 4 nanocomposite could catalyze H 2 O 2 to generate O 2 , thus helping to overcome TME hypoxia and enhancing the photodynamic therapy (PDT) efficacy. Further, the nanocomposites showed excellent T 1 -weighted MRI performance. Our novel use of a pure metal Bi core, offers lower toxicity, higher CT imaging performance, and a photothermal therapy (PTT) effect triggered by 808 nm near infrared (NIR) laser. Moreover, in vivo fluorescence imaging (in vivo FL) vividly showed that the nanocomposite rapidly accumulates in tumor sites due to the enhanced permeability and retention (EPR) effect and metabolized in the organs. The presence of Bi enables the use of these nanocomposites as a CT contrast agent, and the Mn content enables them to be used in MRI. This triple imaging ability implies that our nanocomposites have a high potential for use in imaging directed tumor therapy. Image 1 [ABSTRACT FROM AUTHOR]

• The smart nanoplatform LDH_ZnPcG 4 -FA/DOX was constructed by co-precipitation method. • With NIR irradiation, LDH_ZnPcG 4 -FA/DOX showed excellent antitumor performance in vivo. • The ZnPcG 4 -FA and DOX could be released from LDH_ZnPcG 4 -FA/DOX in acidic TME. • LDH_ZnPcG 4 -FA/DOX could be used as an agent for TME-responsive imaging. Designing a phototherapeutic material that simultaneously has target, tumor microenvironment (TME)-response, high-quality imaging and synergistic therapy has attracted much attention in anticancer field. Herein, a novel stimuli-responsive multifunctional nanoplatform has been constructed by inserting folic acid linked ZnPcG 4 molecules (ZnPcG 4 -FA) into layered double hydroxides (LDH) by a facile co-precipitation method. Subsequently, chemotherapeutic drug (doxorubicin hydrochloride, DOX) was loaded on the surface of LDH (named as LDH_ZnPcG 4 -FA/DOX), which can be released in a controlled and targeted manner with the degradation of LDH in the acidic TME. Upon the 650 nm laser irradiation, this nanoplatform demonstrated excellent anticancer efficiency in vitro and in vivo due to the synergistic chemo-photodynamic therapy derived from the released DOX and ZnPcG 4 photosensitizer (PS). Interestingly, the luminescent ZnPcG 4 -FA in LDH_ZnPcG 4 -FA/DOX exhibited low fluorescence in a neutral environment, while recovered strong fluorescence with the degradation of LDH and release of DOX in acidic TME, implying its TME-responsive imaging property. Besides, in vivo fluorescence imaging of LDH_ZnPcG 4 -FA/DOX represent that the nanoplatform has higher selectivity to tumor cells than normal cells. This study contributes to design a kind of smart "all-in-one" nanoplatform to realize imaging guided synergistic therapy. [ABSTRACT FROM AUTHOR]