Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemo-immunotherapy which combines chemotherapeutics with immune-modulating agents represents an appealing approach to improving cancer therapy [1, 2]. To maximize its efficacy, differential and precise targeting of the multiple therapeutics into corresponding cells is desirable. Here we develop an immunostimulatory nanocarrier that simultaneously loads platinum (Pt)-based chemotherapeutic prodrug and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of tumor-associated macrophages (TAMs) [3], to spatially target tumor cells and TAMs for cancer chemo-immunotherapy. The nanoparticles (denoted as BLZ-945SCNs/Pt) undergo supersensitive structure collapse through responding to tumor acidity, along with instantaneous release of BLZ-945 and Pt-prodrug conjugated small particles. The extracellularly released BLZ-945 could be taken up by TAMs, which locate preferentially in the perivascular region [4], to directly disturb CSF-1/CSF-1R signaling pathway to suppress TAMs and modulate the tumor immune microenvironment, while the released small particles carrying Pt-prodrug could penetrate deeply into bulk tumor to kill more cancer cells [5], realizing synergistic antitumor effect of chemo- and immunotherapy (Fig. 1). Our in vivo studies demonstrate that the co-delivery nanocarrier outperforms monotherapy in varying tumor models.
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PMID:Spatial targeting of tumor-associated macrophage and tumor cells with a designer nanocarrier for cancer chemo-immunotherapy. 2905 67

Immunotherapy has shown promising results in multiple malignancies. However, there are still significant challenges in cancer immunotherapy including the powerful immunosuppressive tumor microenvironment and adverse off-target side effects. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges faced by cancer immunotherapy. Here, a tumor acidity-responsive biomacromolecule delivery system was designed to intratumorally deliver an immune-activating cytokine, macrophage colony-stimulating factor (M-CSF) and attenuate the acidic microenvironment. This nanoparticle was prepared by introducing CaCO3 as a crosslinker to form an M-CSF-loaded stable micelle (NP/M-CSF/CaCO3). Administration of NP/M-CSF/CaCO3 significantly inhibited tumor growth by enhancing T cell-mediated anti-tumor immune responses and reversing the TAM-mediated immunosuppression. This study provides new avenues for cascade amplification of the antitumor effects by targeting the tumor microenvironment. This approach may also help avoid unwanted complications.
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PMID:Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy. 3101 82