Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.

The clinical application of chemodynamic therapyis impeded by the insufficient intracellular H 2 O 2 level in tumor tissues.H erein, we developed as upramolecular nanoparticle via asimple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified b-cyclodextrin-ferrocene conjugates as supramolecular monomers.T he supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H 2 O 2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H 2 O 2 in the tumor tissue.Thus,the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapyvia the self-augmented cascade radical generation and drug release.I na ddition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

Multifunctional nanotheranostic agents have been highly commended due to the application to image-guided cancer therapy. Herein, based on the chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) and graphene oxide (GO), we develop a pH-responsive FePt-based multifunctional theranostic agent for potential in vivo and in vitro dual modal MRI/CT imaging and in situ cancer inhibition. The fcc-FePt will release highly active Fe ions due to the low pH in tumor cells, which would catalyze HO decomposition into reactive oxygen species (ROS) within the cells and further induce cancer cell apoptosis. Conjugated with folic acid (FA), the iron platinum-dimercaptosuccinnic acid/PEGylated graphene oxide-folic acid (FePt-DMSA/GO-PEG-FA) composite nanoassemblies (FePt/GO CNs) could effectively target and show significant toxicity to FA receptor-positive tumor cells, but no obvious toxicity to FA receptor-negative normal cells, which was evaluated by WST-1 assay. The FePt-based multifunctional nanoparticles allow real-time monitoring of Fe release by T-weighted MRI, and the selective contrast enhancement in CT could be estimated in vivo after injection. The results showed that FePt-based NPs displayed excellent biocompatibility and favorable MRI/CT imaging ability in vivo and in vitro. Meanwhile, the decomposition of FePt will dramatically decrease the T-weighted MRI signal and increase the ROS signal, which enables real-time and in situ visualized monitoring of Fe release in tumor cells. In addition, the self-sacrificial decomposition of fcc-FePt will be propitious to the self-clearance of the as-prepared FePt-based nanocomposite in vivo. Therefore, the FePt/GO CNs could serve as a potential multifunctional theranostic nanoplatform of MRI/CT imaging guided cancer diagnosis and therapy in the clinic.

Mitochondrial fission is often associated with the development of oxidative stress related diseases, as the fragmentation of mitochondria undermines their membranes, advances production of reactive oxygen species, and promotes apoptosis. Therefore, induction of mitochondrial aggregation and fusion could potentially reverse such medical conditions. Herein, a supramolecular strategy to induce mitochondrial aggregation and fusion is developed for the first time. A polyethylene glycol (PEG) system that was dually tagged with triphenylphosphonium (TPP) and adamantane (ADA), namely TPP-PEG-ADA, was designed to target mitochondria and functionalize their surfaces with ADA. Thereafter, the addition of cucurbit[7]­uril (CB[7]) grafted hyaluronic acid (HA) induced supramolecular aggregation and fusion of mitochondria, via strong host–guest interactions between the CB[7] moiety of CB[7]-HA and ADA residing on the surface of mitochondria. As a proof-of-principle, chemically stressed SH-SY5Y cells and zebrafish neurons were effectively protected via this supramolecular mitochondrial fusion strategy in vitro and in vivo, respectively. This study may open up new venues in not only fundamentally controlling mitochondrial dynamics but also addressing the medical needs to treat diseases associated with mitochondrial fission and fragmentation.

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Ulcerative colitis (UC) is featured with relapsing inflammation in the colon, where macrophages are recruited and polarized locally into M1 type to drive further inflammation. Pharmacotherapy of UC has exhibited limited efficacy, mostly due to the poor specificity. Methods: A macrophage-biomimetic nanomedicine was developed for targeted treatment of UC, which was derived from reactive oxygen species (ROS)-sensitive β-cyclodextrin, loaded with rosiglitazone, and coated with macrophage membrane. The ability of the nanomedicine in regulating macrophage polarization was examined at cellular level, and the macrophage-tropism driven targeted delivery into the inflammatory colon was investigated by ex vivo bio-imaging distribution assay. Furthermore, the nanomedicine's therapeutic efficacy was systemically examined in dextran sulfate sodium (DSS)-induced colitis model in mice. Results: The nanomedicine effectively polarized macrophages to M2 and protected epithelial cells from oxidative stress in vitro . In addition, macrophage-membrane led the nanomedicine to the inflammatory colon with a high targeting efficiency. In response to the elevated ROS in the inflammatory tissue, the nanomedicine released rosiglitazone specifically and regulated macrophage polarization in vivo . Macrophage membrane also assisted inflammation suppression by sequestering proinflammatory cytokines. Working in such a synergy, the nanomedicine exhibited significant therapeutic effects against UC in mice. Conclusions: This macrophage-biomimetic nanomedicine leverages the inflammatory tropism and inflammatory cytokine sequestration effects of macrophage membrane for targeted delivery and local inflammation suppression, the ROS-responsiveness of β-cyclodextrin-based matrix for specific payload release, and the macrophage-polarizing effect of rosiglitazone for inflammatory regulation, thereby exhibiting considerable therapeutic efficacy against UC in mice. This study offers important new insights on the design and development of biomimetic nanomaterials for inflammation regulations.

Immunological tolerance induced by the hypoxic tumor microenvironment has been a major challenge for current immune checkpoint blockade therapies. Here, a hypoxia‐responsive drug delivery nanoplatform is reported to promote chemoimmunotherapy of cancer by overcoming the hypoxia‐induced immunological tolerance of tumors. The nanovesicles are assembled from manganese ferrite nanoparticles (MFNs) grafted with hypoxia‐responsive amphiphilic polymers as the membrane, with doxorubicin hydrochloride (Dox) loaded in the aqueous cavities. Under hypoxic conditions in tumors, the nanovesicles can rapidly dissociate into individual MFNs to release Dox and induce decomposition of tumor endogenous H2O2 for tumor hypoxia relief. As a result, the Dox‐loaded nanovesicles display remarkable suppression of primary tumor growth in combination with αPD‐L1‐mediated checkpoint blockade therapy. Furthermore, the modulation of the hypoxic tumor microenvironment facilitates a long‐lasting immunological memory effect to prevent tumor recurrence and metastasis. Therefore, this hypoxia‐responsive nanoplatform presents a potential strategy for both local tumor treatment and long‐term protection against tumor recurrence.

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