Nanosized calcium carbonate particles were prepared with a continuous gas-liquid membrane contactor. The effects of Ca(OH)2 concentration, CO2 pressure and liquid flow velocity on the particles morphology, pressure dr...Nanosized calcium carbonate particles were prepared with a continuous gas-liquid membrane contactor. The effects of Ca(OH)2 concentration, CO2 pressure and liquid flow velocity on the particles morphology, pressure drop and membrane fouling were studied. With rising Ca(OH)2 concentrations, the average size of the particles increased. The effects of Ca(OH)2 concentration and CO2 pressure on particles were not apparent under the experimental conditions. When the Ca(OH)2 concentration and liquid flow velocity were high, or the CO2 pressure was low, the fouling on the membrane external surface at the contactor entrance was serious due to liquid leakage, whereas the fouling was slight at exit. The fouling on the membrane inner-surface at entrance was apparent due to adsorption of raw materials. The membrane can be recovered by washing with dilute hydrochloric acid and reused for at least 6 times without performance deterioration.展开更多
Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strong...Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.展开更多
基金Supported by the National Natural Science Foundation of China （20676016, 21076024）.
文摘Nanosized calcium carbonate particles were prepared with a continuous gas-liquid membrane contactor. The effects of Ca(OH)2 concentration, CO2 pressure and liquid flow velocity on the particles morphology, pressure drop and membrane fouling were studied. With rising Ca(OH)2 concentrations, the average size of the particles increased. The effects of Ca(OH)2 concentration and CO2 pressure on particles were not apparent under the experimental conditions. When the Ca(OH)2 concentration and liquid flow velocity were high, or the CO2 pressure was low, the fouling on the membrane external surface at the contactor entrance was serious due to liquid leakage, whereas the fouling was slight at exit. The fouling on the membrane inner-surface at entrance was apparent due to adsorption of raw materials. The membrane can be recovered by washing with dilute hydrochloric acid and reused for at least 6 times without performance deterioration.
基金supported by the Key R&D Program of Lishui City(2021ZDYF12,2022ZDYF07,2023zdyf14)Natural Science Foundation of China(82072026,82072025 and 82272090)+1 种基金Zhejiang Provincial Natural Science Foundation(LY23H180003,LQ22H180010)Provincial and Ministerial Joint Construction of Key Projects(WKJ-ZJ-2317).
文摘Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.
