Advances in nanomaterials for treatment of hypoxic tumor.

The hypoxic tumor microenvironment is characterized by disordered vasculature and rapid proliferation of tumors, resulting from tumor invasion, progression and metastasis. The hypoxic conditions restrict efficiency of tumor therapies, such as chemotherapy, radiotherapy, phototherapy and immunotherapy, leading to serious results of tumor recurrence and high mortality. Recently, research has concentrated on developing functional nanomaterials to treat hypoxic tumors. In this review, we categorize such nanomaterials into (i) nanomaterials that elevate oxygen levels in tumors for enhanced oxygen-dependent tumor therapy and (ii) nanomaterials with diminished oxygen dependence for hypoxic tumor therapy. To elevate oxygen levels in tumors, oxygen-carrying nanomaterials, oxygen-generating nanomaterials and oxygen-economizing nanomaterials can be used. To diminish oxygen dependence of nanomaterials for hypoxic tumor therapy, therapeutic gas-generating nanomaterials and radical-generating nanomaterials can be used. The biocompatibility and therapeutic efficacy of these nanomaterials are discussed.

Artificial Natural Killer Cells for Specific Tumor Inhibition and Renegade Macrophage Re-Education.

Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re-educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re-education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H2 O2 ). The generated H2 O2 is also similar to cytokines and chemokines for recruiting immune cells and re-educating survived macrophages to attack tumor cells. In addition, the oxygen-carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.

Nanoparticles from Cuttlefish Ink Inhibit Tumor Growth by Synergizing Immunotherapy and Photothermal Therapy.

Natural nanoparticles have been extensively studied due to their diverse properties and easy accessibility. Here, the nanoparticles extracted from cuttlefish ink (CINPs) with significant antitumor efficacy are explored. These CINPs, with spherical morphology, good dispersibility, and biocompatibility, are rich in melanin and contain a variety of amino acids and monosaccharides. Through the activation of mitogen-activated protein kinase (MAPK) signaling pathway, CINPs can efficiently reprogram tumor-associated macrophages (TAMs) from immune-suppressive M2-like phenotype to antitumor M1-like phenotype. Besides, under near-infrared (NIR) irradiation, CINPs exhibit high photothermal effect and tumor cell killing ability, which make them a potential candidate in photothermal therapy (PTT) of tumor. In vivo, CINPs can increase the proportion of M1 macrophages and foster the recruitment of cytotoxic T lymphocytes (CTLs) to tumors, leading to reduced primary tumor growth and lung metastasis. In combination with their photothermal effect, which can induce tumor-specific antigens release, CINPs could almost completely inhibit tumor growth accompanied by more active immune responses. Collectively, these CINPs described here can provide both tumor immunotherapy and PTT, implying that CINPs are promising for tumor treatment.