As traditional anticancer treatments fail to significantly improve the prognoses, exploration of therapeutic modalities is urgently needed. Herein, a biomimetic magnetosome is constructed to favor the ferroptosis/immunomodulation synergism in cancer. This magnetosome is composed of an Fe3O4 magnetic nanocluster (NC) as the core and pre-engineered leukocyte membranes as the cloak, wherein TGF-β inhibitor (Ti) can be loaded inside the membrane and PD-1 antibody (Pa) can be anchored on the membrane surface. After intravenous injection, the membrane camouflage results in long circulation, and the NC core with magnetization and superparamagnetism enables magnetic targeting with magnetic resonance imaging (MRI) guidance. Once inside the tumor, Pa and Ti cooperate to create an immunogenic microenvironment, which increases the amount of H2O2 in polarized M1 macrophages and thus promotes the Fenton reaction with Fe ions released from NCs. The generated hydroxyl radicals (•OH) subsequently induce lethal ferroptosis to tumor cells, and the exposed tumor antigen, in turn, improves the microenvironment immunogenicity. The synergism of immunomodulation and ferroptosis in such a cyclical manner therefore leads to potent therapeutic effects with few abnormalities, which supports the engineered magnetosomes as a promising combination modality for anticancer therapy.

As a type of programmed cell death, ferroptosis is distinct from apoptosis. The combination of the two thus provides a promising modality with which to significantly improve anticancer treatment efficacy. To fully utilize this combination, we herein designed a nanolongan delivery system, which possessed a typical structure of one core (up-conversion nanoparticles, UCNP) in one gel particle (Fe3+ cross-linked oxidized starch) with multiple on-demand conversions. The charge conversion of the nanolongan surface in a slightly acidic microenvironment enhanced circulation time for utilizing the enhanced permeability and retention effect, enabled efficient uptake by tumor cells, and induced subsequently lysosomal escape. As the core component, the UCNP with light conversion from near-infrared light to ultraviolet light circumvented the impediment of limited penetration depth and enabled the reduction of Fe3+ to Fe2+. Accordingly, gel networks of nanolongan could be deconstructed due to this valence conversion, leading to the rapid release of Fe2+ and doxorubicin (Dox). In this case, the Fenton reaction between Fe2+ and intracellular H2O2 generated potent reactive oxygen species for ferroptosis, while the co-released Dox penetrated into nucleus and induced apoptosis in a synergistic way. As a result, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that our nanolongan could serve as a safe and high-performance platform for ferroptosis–apoptosis combined anticancer therapy.

A novel cancer vaccine is developed by using Fe 3 O 4 magnetic nanoclusters (MNCs) as the core and cancer cell membranes decorated with anti-CD205 as the cloak. Because of the superparamagnetism and magnetization of MNCs, it is first achieved for the magnetic retention of vaccine in the lymph nodes with a magnetic resonance imaging (MRI) guide, which opened the time window for antigen uptake by dendritic cells (DCs). Meanwhile, the camouflaged cancer cell membranes serve as a reservoir of various antigens, enabling subsequent multiantigenic response. Additionally, the decorated anti-CD205 direct more vaccine into CD8 + DCs, facilitating the major histocompatibility complex (MHC) I cross-presentation. These unique advantages together lead to a great proliferation of T cells with superior clonal diversity and cytotoxic activity. As a result, potent prophylactic and therapeutic effects with few abnormalities are observed on five different tumor models. Therefore, such a cancer-derived magnetosome with the integration of various recent nanotechnologies successfully demonstrates its promise for safe and high-performance cancer vaccination.

A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.