Sonodynamic therapy (SDT) is a noninvasive technique for local antitumor treatment; however, its clinical application is often limited by the low tumor accumulation of SDT agents, tumor's hypoxic microenvironment, and cytoprotective effects of autophagy. To address these issues, herein we developed surface-engineered chlorella (Chl, a green algae) as a targeted drug carrier and sustainable oxygen supplier (via photosynthesis) for significantly improved SDT via hypoxia alleviation as well as autophagy inhibition of chloroquine phosphate. In this design, the macrophage membrane was coated onto Chl to form macrophage-mimetic Chl (MChl) to increase its biocompatibility and targeted tumor accumulation driven by the inflammatory-homing effects of macrophage membranes. In addition, the membrane coating on Chl allowed lipid insertion to yield β-cyclodextrin (β-CD) modified MChl (CD-MChl). Subsequently, supramolecular conjugates of MChl-NP were constructed via host−guest interactions between CD-MChl and adamantane (ADA)-modified liposome (ADA-NP), and the anchored liposome went with CD-MChl hand-in-hand to the tumor tissues for co-delivery of Chl, hematoporphyrin, and chloroquine phosphate (loaded in ADA-NP). The synergistic therapy achieved via local oxygenation, SDT, and autophagy inhibition maximally improved the therapeutic efficacy of MChl-CQ-HP-NP against melanoma. Tumor rechallenging results revealed that the changes of tumor microenvironment including hypoxia alleviation, SDT induced immunogenic cell death, and autophagy inhibition collectively induced a strong antitumor immune response and memory.
Ultrathin MnO2 hollow nanoballoons (UMHNBs) have a large ratio of interfacial to total atoms, corresponding to expected improved performance. However, their synthesis is a challenge due to difficulty in controlling the concentration of the unit cells. Herein, we describe a strategy to synthesize dry intact UMHNBs through a one-step synthesis by inflating MnO2 (reduced from KMnO4) with CO2 (oxidized from single-layer graphene oxide nanosheets) followed by instant freeze-drying. UMHNBs are 30-500 nm in diameter with a shell thickness of 3.7 nm, packing with laminar [MnO6] unit cells in the form of δ-MnO2. UMHNBs show efficient catalytic activity for decomposing the organic dye methylene blue (MB), 15 times the biggest reported value, and have long-term catalytic efficacy and durability. The described strategy in this paper makes use of graphene nanosheets to assemble durable ultrathin hollow nanoballoons.
Cell-based drug carriers are mostly prepared in vitro, which may negatively affect the physiological functions of cells, and induce possible immune rejections when applied to different individuals. In addition, the immunosuppressive tumor microenvironment limits immune cell–mediated delivery. Here, we report an in vivo strategy to construct cell-based nanomedicine carriers, where bacteria-mimetic gold nanoparticles (GNPs) are intravenously injected, selectively phagocytosed by phagocytic immune cells, and subsequently self-assemble into sizable intracellular aggregates via host-guest interactions. The intracellular aggregates minimize exocytosis of GNPs from immune cells and activate the photothermal property via plasmonic coupling effects. Phagocytic immune cells carry the intracellular GNP aggregates to melanoma tissue via inflammatory tropism. Moreover, an initial photothermal treatment (PTT) of the tumor induces tumor damage that subsequently provides positive feedback to recruit more immune cell–based carriers for enhanced targeting efficiency. The optimized secondary PTT notably improves antitumor immunotherapy, further strengthened by immune checkpoint blockade.
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