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
From 1924 to1926,with the CitéFrugès in Pessac,Le Corbusier and Pierre Jeanneret realized an urban area as a laboratory where research on architecture polychromy was achieved among others.Colored facade was ...From 1924 to1926,with the CitéFrugès in Pessac,Le Corbusier and Pierre Jeanneret realized an urban area as a laboratory where research on architecture polychromy was achieved among others.Colored facade was applied as a tool to modify urban space.This neighbourhood has always been inhabited and transformed by its inhabitants over time.In the 90’s,studies for the global image protection of the neighbourhood included polychromy research conducted to restore the shades of origin.However,the colors have often been interpreted in various ways.Nowadays,besides the shade problems,other challenges have arisen linked to the preservation of the facade materials.This paper presents the recent archive research done to clarify the shade references and lay the groundwork so as to choose the right material to use and further research in the future.展开更多
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.
文摘From 1924 to1926,with the CitéFrugès in Pessac,Le Corbusier and Pierre Jeanneret realized an urban area as a laboratory where research on architecture polychromy was achieved among others.Colored facade was applied as a tool to modify urban space.This neighbourhood has always been inhabited and transformed by its inhabitants over time.In the 90’s,studies for the global image protection of the neighbourhood included polychromy research conducted to restore the shades of origin.However,the colors have often been interpreted in various ways.Nowadays,besides the shade problems,other challenges have arisen linked to the preservation of the facade materials.This paper presents the recent archive research done to clarify the shade references and lay the groundwork so as to choose the right material to use and further research in the future.
