Weak acidity (6.5-6.9) and limited H2O2 level in the tumor microenvironment (TME) usually impact the therapeutic effect of chemodynamic therapy (CDT) for cancer. A Specific TME promotes the formation of an immunosuppressive microenvironment and results in high rate of recurrence and metastasis of cancer. Fe3O4@ZIF-8/GOx@MnO2 multi-layer core shell nanostructure was constructed as a hybrid nanozyme. After magnetic targeting of the tumor site, the outermost MnO2 shell catalyzed H2O2 in TME to produce O2 and was broken due to the reaction with glutathione. Due to the acid response, the ZIF-8 layer would crack and release glucose oxidase (GOx) and Fe3O4. The generated O2 was utilized by GOx in starvation therapy to consume glucose and produce H2O2 and gluconic acid. The Fenton reaction efficiency of Fe(II) was improved by the increased H2O2 concentration and the enhanced acidity in TME. At the same time, the intrinsic photothermal effect of Fe3O4 upon 808 nm laser irradiation promoted the activity of MnO2 and GOx as oxidase, and Fe(II) as catalase-like, and ablated the primary tumor. Moreover, the hybrid nanozyme can facilitate the transformation of M2-type macrophages to M1-type, and strong systemic antitumor immune effect was induced. A synergy of multiple therapeutic modes including starvation therapy, CDT, photothermal therapy (PTT), and immunotherapy can be realized in the hybrid nanozyme for tumor therapy.

A multimodal strategy of Fe3O4@ZIF-8/GOx@MnO2 hybrid nanozyme via TME modulation for tumor therapy

For efficient cancer theranostics, surface modification of nanomaterials plays an important role in improving targeting ability and reducing the non-specific interactions with normal tissues. Recently, the biomimetic technology represented by coating of cancer cell membranes (CCMs) has been regarded as a promising method to strengthen the biocompatibility and targeting specificity of nanomaterials. Furthermore, the engineered CCMs (ECCMs) integrated with the natural biological properties of CCMs and specific functions from other cells or proteins have offered more possibilities in the field of cancer theranostics. Herein, the recent progresses in the design and preparation of ECCMs are summarized, and the applications of ECCMs in targeting delivery, activation of immunity, and detection of circulating tumor cells are reviewed. Finally, the current challenges and future perspectives with regard to the development of ECCMs are briefly discussed. 

Engineered cancer cell membranes: An emerging agent for efficient cancer theranostics

Sulfur-Regulated Defect Engineering for Enhanced Ultrasonic Piezocatalytic Therapy of Bacteria-Infected Bone Defects

Much effort is devoted to develop agents with superior photoacoustic/photothermal properties for improved disease diagnosis and treatment. Herein, a new fused two isoindigo (DIID)‐based semiconducting conjugated polymer (named PBDT‐DIID) is rationally designed and synthesized with a strong near‐infrared absorption band ranging from 700 to 1000 nm. Water‐dispersing nanoparticles (NPs) of PBDT‐DIID are prepared with good biocompatibility and a rather high photothermal conversion efficiency (70.6%), as the active excited‐state intramolecular twist around the central double bonds in DIID permits most of the absorbed excitation energy flow to heat deactivation pathway through internal conversion. The photoacoustic signal can be further magnified by incorporation of polylactide (PLA) in the NP core to confine the generated heat of PBDT‐DIID within NPs. The resultant doped NPs show excellent performance in photoacoustic imaging‐guided photothermal therapy in an orthotopic 4T1 breast tumor‐bearing mouse model. It is also found that the photothermal effect of the PBDT‐DIID NPs is safe and quite efficacious to highly improve the root canal treatment outcome by heating the 1% NaClO solution inside the root canal upon 808 nm laser irradiation in a human extracted tooth root canal infection model.

Semiconducting Polymer Nanoparticles with Intramolecular Motion‐Induced Photothermy for Tumor Phototheranostics and Tooth Root Canal Therapy

Nanomedicine potentiates mild photothermal therapy for tumor ablation

Liquid exfoliation of TiN nanodots as novel sonosensitizers for photothermal-enhanced sonodynamic therapy against cancer

Magnetic hyperthermia therapy (MHT) is able to ablate tumors using an alternating magnetic field (AMF) to heat up magnetocaloric agents (e.g. magnetic nanoparticles) administered into the tumors. For clinical applications, there is still a demand to find new magnetocaloric agents with strong AMF-induced heating performance and excellent biocompatibility. As a kind of biocompatible and biodegradable material, magnesium (Mg) and its alloys have been extensively used in the clinic as an implant metal. Herein, we discovered that the eddy thermal effect of the magnesium alloy (MgA) could be employed for MHT to effectively ablate tumors. Under low-field-intensity AMFs, MgA rods could be rapidly heated, resulting in a temperature increase in nearby tissues. Such AMF-induced eddy thermal heating of MgA could not only be used to kill tumor cells in vitro, but also be employed for effective and accurate ablation of tumors in vivo. In addition to killing tumors in mice, we further demonstrated that VX2 tumors of much larger sizes growing in rabbits after implantation of MgA rods could also be eliminated after exposure to an AMF, illustrating the ability of MgA-based MHT to kill large-sized tumors. Moreover, the implanted MgA rods showed excellent biocompatibility and ∼20% of their mass was degraded within three months. Our work thus discovered for the first time that non-magnetic biodegradable MgA, an extensively used implant metal in clinic, could be used for effective magnetic thermal ablation of tumors under a low-field-intensity AMF. Such a strategy could be readily translated into clinical use.

Biodegradable magnesium alloy with eddy thermal effect for effective and accurate magnetic hyperthermia ablation of tumors.

The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade. With inherent biocompatibility, nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications. Herein, we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment. We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics, and then discuss the applications of biological membrane derived nanomedicines. For the first major category of membrane-derived nanomedicine, synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities. The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment. At last, we discuss the challenges of membrane-derived nanomedicines towards future clinical applications, following with perspectives on possible solutions to the current problems.

Zhanhui Wang

Papers

Liquid exfoliation of TiN nanodots as novel sonosensitizers for photothermal-enhanced sonodynamic therapy against cancer

Biodegradable magnesium alloy with eddy thermal effect for effective and accurate magnetic hyperthermia ablation of tumors.

Biological membrane derived nanomedicines for cancer therapy