Promote Intratumoral Drug Release and Penetration to Counteract Docetaxel‐Induced Metastasis by Photosensitizer‐Modified Red Blood Cell Membrane‐Coated Nanoparticle
Abstract:The red blood cell membrane (RBCm) provides tight protection, lowers the immunogenicity, and prolongs the circulation time of drugs in vivo when acting as the coating of drug delivery systems. However, the cellular uptake and release of drugs are hindered by RBCm. Docetaxel (DTX) is the first-line medicine for treating triple-negative breast cancer (TNBC), but it induces tumor metastasis. To solve these dilemmas, in this study, the photosensitizer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (… Show more
“…5I). 34,35 Among all groups, the Ce6/HDP + L group possessed the highest concentration of IFN-γ, which was consistent with the results of the rate of DC maturation. These results verified that the Ce6/HDP NPs with laser irradiation efficiently induced ICD and promoted the in vivo maturation of DCs.…”
Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy,...
“…5I). 34,35 Among all groups, the Ce6/HDP + L group possessed the highest concentration of IFN-γ, which was consistent with the results of the rate of DC maturation. These results verified that the Ce6/HDP NPs with laser irradiation efficiently induced ICD and promoted the in vivo maturation of DCs.…”
Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy,...
“…The drug‐loading capacity of the particles was determined (Figure S2, Supporting Information) at various feeding ratios, and the mass feeding ratio (MTO:PPE) of 1:10 was used in subsequent experiment. Then, the RBC membrane was collected from BALB/c mice, according to the protocol reported in a previous study [ 27–29 ] and used to coat the obtained PPE MTO . After optimization, the weight ratio of cell membrane to polymer was set at 1.0 to obtain stable biomimetic nanomedicine RBC@PPE MTO .…”
Metastatic triple‐negative breast cancer (TNBC) has a poor prognosis and high mortality with no effective treatment options, and immunotherapy is highly anticipated as a potential treatment but is limited by the lack of tumor‐infiltrating T lymphocytes in TNBC. Herein, red blood cell (RBC) membrane‐camouflaged polyphosphoester (PPE) nanoparticles (RBC@PPEMTO/PFA) are prepared as the nanocarriers of mitoxantrone (MTO) and perfluoroalkane (PFA) for synergized immunotherapy. The encapsulated MTO can generate heat and reactive oxygen species (ROS) to achieve photothermal and photodynamic therapy; moreover, ROS further triggers the self‐accelerating release of MTO from the ROS‐sensitive PPE core to enable chemotherapy. The RBC@PPEMTO/PFA‐mediated sequential photothermal/photodynamic/chemotherapy efficiently promotes the infiltration of CD8+ T cells into TNBC tumor tissue and synergizes the therapeutic activity of an immune checkpoint blockade antibody for metastatic TNBC treatment in distant and lung metastasis models. This biomimetic nanomedicine of MTO provides a convenient and available strategy to sensitize TNBC to immune checkpoint blockade antibody.
“…RBC membranes were extracted from female BALB/c nude mice as described in previous reports. − Briefly, whole blood was collected in PBS (1×, pH = 7.4) containing heparin sodium. RBCs were isolated via centrifugation (3000 rpm, 5 min, 4 °C), and the supernatant and white chorion layer were removed.…”
Nanomedicines for combining chemotherapy and sonodynamic
therapy
(SDT) have enormous potential in squamous cell carcinoma treatment.
However, the therapeutic efficacy of noninvasive SDT is severely limited
because the generation of reactive oxygen species (ROS) by sonosensitizers
is highly dependent on the levels of intracellular excess glutathione
(GSH) in the tumor cells. To overcome this barrier, a red blood cell
(RBC) membrane-camouflaged nanomedicine consisting of GSH-sensitive
polyphosphoester (SS-PPE) and ROS-sensitive polyphosphoester (S-PPE)
was designed for the simultaneous delivery of the sonosensitizer hematoporphyrin
(HMME) and chemotherapeutic agent docetaxel (DTXL) for effectively
enhanced antitumor efficacy. In vitro and in vivo studies demonstrated that HMME-driven ROS generation
under ultrasound (US) inhibited SCC7 cell proliferation and accelerated
DTXL release to further kill tumor cells via the
hydrophobic–hydrophilic transition of the nanoparticle core.
Meanwhile, the disulfide bond of SS-PPE effectively consumes GSH to
prevent ROS consumption. This biomimetic nanomedicine provides GSH
depletion and amplified ROS generation capabilities to achieve a novel
synergistic chemo-SDT strategy for squamous cell carcinomas.
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