Conventional oxygen‐dependent photodynamic therapy (PDT) has faced severe challenges because of the non‐specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. Here, an O2 self‐sufficient cell‐like biomimetic nanoplatform (CAT‐PS‐ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton‐like porous zeolitic imidazolate framework (ZIF‐8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT‐PS‐ZIF@Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H2O2 penetration into the framework, it is catalyzed by CAT to produce O2 at the hypoxic tumor site, facilitating the generation of toxic 1O2 for highly effective PDT in vivo under near‐infrared irradiation. By integrating the immune escape, cell homologous recognition, and O2 self‐sufficiency, this cell‐like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side‐effect on normal tissues.
In this paper, a simple, but effective method is reported to construct the core−shell gold nanorod@metal–organic frameworks (AuNR@MOFs) as a multifunctional theranostic platform by using functionalized AuNRs as seed crystal for the growth of porphyrinic MOFs on the surface of AuNR. Such a delicate tunable core−shell composite not only possesses the improved drug loading efficiency, near‐infrared light‐trigger drug release, and fluorescence imaging, but also can produce reactive oxygen species as well as photothermal activity to achieve combined cancer therapy. It is further demonstrated that the camptothecin loaded AuNR@MOFs show distinctively synergistic efficiency for damaging the cancer cell in vitro and inhibiting the tumor growth and metastasis in vivo. The development of this high‐performance incorporated nanostructure will provide more perspectives in the design of versatile nanomaterials for biomedical applications.
Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.
Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co‐stimulatory molecules for robust immunotherapy. FMs share the tumor's self‐targeting character with the parent cancer cells. In bilateral tumor‐bearing mouse models, the FM‐coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post‐nanophotosensitizer‐induced photodynamic therapy (PDT). The FM‐induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy‐caused regression of the irradiation‐free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor‐specific immunotherapy‐based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.
We report on the benzoporphyrin-based metal-organic framework (TBP-MOF), with 10-connected Zr cluster and much improved photophysical properties over the traditional porphyrin-based MOFs. It was found that TBP-MOF exhibited red-shifted absorption bands and strong near-infrared luminescence for bioimaging, whereas the π-extended benzoporphyrin-based linkers of TBP-MOF facilitated O generation to enhance O-dependent photodynamic therapy (PDT). It was demonstrated that poly(ethylene glycol)-modified nanoscale TBP-MOF (TBP-nMOF) can be used as an effective PDT agent under hypoxic tumor microenvironment. We also elucidated that the low O-dependent PDT of TBP-nMOF in combination with αPD-1 checkpoint blockade therapy can not only suppress the growth of primary tumor, but also stimulate an antitumor immune response for inhibiting metastatic tumor growth. We believe this TBP-nMOF has great potential to serve as an efficient photosensitizer for PDT and cancer immunotherapy.
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