Mineralized Porphyrin Metal-Organic Framework for Improved Tumor Elimination and Combined Immunotherapy.

Calcium ion therapy is a potential anticancer treatment. However, the cellular calcium-buffering mechanism limited the effectiveness of calcium ion therapy. Here, we constructed a mineralized porphyrin metal-organic framework (PCa) to produce calcium ions and reactive oxygen species (ROS), which destroyed cell calcium buffering capacity and amplified the cell damage caused by calcium overload.

Self-Reinforced Cancer Targeting (SRCT) Depending on Reciprocally Enhancing Feedback between Targeting and Therapy.

Conventional cancer targeting methodology needs to be reformed to overcome the intrinsic barriers responsible for poor targeting efficiency. This study describes a concept of self-reinforced cancer targeting (SRCT) by correlating targeting with therapy in a reciprocally enhancing manner. SRCT is achieved on the basis of two prerequisites: (1) target molecules have to be expressed on cancer cell membranes but not on normal cells, and (2) notably, their expression on cancer cells must be actively upregulated in response to cellular attack by cancer treatments.

A HO-responsive theranostic platform for chemiluminescence detection and synergistic therapy of tumors.

Chemiluminescence substances that respond to hydrogen peroxide (HO) in a tumor microenvironment have the potential to achieve accurate tumor imaging. Here, Pluronic F-127 (PF127) and polymers containing oxalate ester (POE) were assembled by hydrophilic and hydrophobic forces to form nanoparticles to load the anti-tumor drug lapachone (Lapa) and rubrene. The Lapa-loaded HO-responsive nanoparticles (L-HPOX) could track tumors through HO-related chemiluminescence.

Large π-Conjugated Metal-Organic Frameworks for Infrared-Light-Driven CO Reduction.

It remains challenging to excite traditional photocatalysts through near-infrared (NIR) light. Attempts to use NIR-light-response materials for photochemical reduction usually suffer from inapposite band position due to extremely narrow band gaps. Here, we report that large π-conjugated organic semiconductor engineered metal-organic framework (MOF) can result in NIR-light-driven CO reduction catalyst with high photocatalytic activity.

A near infrared ratiometric platform based π-extended porphyrin metal-organic framework for O imaging and cancer therapy.

Photodynamic therapy (PDT) is widely researched in tumor treatment, but its therapeutic effect is affected by oxygen (O) concentration of tumor site. Here, we developed a Pd-coordinated π-conjugated extended porphyrin doped porphyrin metal-organic-framework (named as PTP). PTP can achieve near infrared (NIR) O concentration ratiometric imaging, solving the problems of short detection wavelengths and influence of self-concentrations.

Integration of a porous coordination network and black phosphorus nanosheets for improved photodynamic therapy of tumor.

Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms.

Covalent Organic Framework for Improving Near-Infrared Light Induced Fluorescence Imaging through Two-Photon Induction.

Fluorescent materials exhibiting two-photon induction (TPI) are used for nonlinear optics, bioimaging, and phototherapy. Polymerizations of molecular chromophores to form π-conjugated structures were hindered by the lack of long-range ordering in the structure and strong π-π stacking between the chromophores. Reported here is the rational design of a benzothiadiazole-based covalent organic framework (COF) for promoting TPI and obtaining efficient two-photon induced fluorescence emissions.

Immobilized liquid metal nanoparticles with improved stability and photothermal performance for combinational therapy of tumor.

Various negative effects accompanying with the instability of bare liquid metal (LM) nanoparticles, including undesirable spontaneous coalescence, continuous photothermal performance deterioration and difficult multi-step functionalization, severely hinder its applications in biomedical area. In this study, we proposed a new concept of immobilized liquid metal nanoparticles based on a surface mesoporous silica coating strategy (LM@MSN). Strikingly, it was found that unsteady and vulnerable LM nanoparticles after immobilization exhibited enhanced stabilization and sustainable photothermal performance even with a long and repeated light irradiation in acidic environments.

A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy.

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (HO)-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery.

A two-photon excited O-evolving nanocomposite for efficient photodynamic therapy against hypoxic tumor.

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-CN) for the first time. While exposured to two-photon laser, Ru(bpy) was activated to generate singlet oxygen (O) and Fe-CN was triggered to split water for oxygen supply in the mean time.

Real-Time Imaging of Free Radicals for Mitochondria-Targeting Hypoxic Tumor Therapy.

Free radicals have emerged as new-type and promising candidates for hypoxic tumor treatment, and further study of their therapeutic mechanism by real-time imaging is of great importance to explore their biomedical applications. Herein, we present a smart free-radical generator AuNC-V057-TPP for hypoxic tumor therapy; the AuNC-V057-TPP not only exhibits good therapeutic effect under both hypoxic and normoxic conditions but also can monitor the release of free radicals in real-time both in vitro and in vivo. What is more, with the mitochondria-targeting ability, the AuNC-V057-TPP is demonstrated with improved antitumor efficacy through enhanced free radical level in mitochondria, which leads to mitochondrial membrane damage and ATP production reduction and finally induces cancer cell apoptosis.

A self-delivery membrane system for enhanced anti-tumor therapy.

Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications.

A biomimetic theranostic O-meter for cancer targeted photodynamic therapy and phosphorescence imaging.

In this report, a biomimetic theranostic oxygen (O)-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability.

Cancer Cell Membrane Camouflaged Cascade Bioreactor for Cancer Targeted Starvation and Photodynamic Therapy.

Selectively cuting off the nutrient supply and the metabolism pathways of cancer cells would be a promising approach to improve the efficiency of cancer treatment. Here, a cancer targeted cascade bioreactor (designated as mCGP) was constructed for synergistic starvation and photodynamic therapy (PDT) by embedding glucose oxidase (GOx) and catalase in the cancer cell membrane-camouflaged porphyrin metal-organic framework (MOF) of PCN-224 (PCN stands for porous coordination network). Due to biomimetic surface functionalization, the immune escape and homotypic targeting behaviors of mCGP would dramatically enhance its cancer targeting and retention abilities.

Multi-Förster Resonance Energy Transfer-Based Fluorescent Probe for Spatiotemporal Matrix Metalloproteinase-2 and Caspase-3 Imaging.

A novel single-molecular fluorescent probe was developed for spatiotemporal matrix metalloproteinase-2 (MMP-2) and caspase-3 imaging with distinct fluorescence signals. Due to the multi-Förster resonance energy transfer (FRET) processes, the probe could respond to MMP-2 and caspase-3 independently with high signal-to-noise ratio. Moreover, the overexpression of MMP-2 in cancer cell lines and the cisplatin induced cell apoptosis were spatiotemporal imaged with distinct fluorescence emissions.

A ratiometric theranostic probe for tumor targeting therapy and self-therapeutic monitoring.

Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Förster resonance energy transfer (FRET) based theranostic probe was fabricated for simultaneous tumor targeting PDT and ratiometric imaging of the therapeutic effect. The theranostic probe (designated as P-PpIX) was comprised of a targeting moiety, a caspase-3 responsive linker, a FRET fluorophore pair and a photosensitizer.

Protease-Activable Cell-Penetrating Peptide-Protoporphyrin Conjugate for Targeted Photodynamic Therapy in Vivo.

In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT).