Cisplatin resistance is the main cause for the failure of cancer therapy.To solve the problem,we proposed to develop a novel human serum albumin(HSA)nanoplatform to integrate chemotherapy,photothermal therapy(PTT)and ...Cisplatin resistance is the main cause for the failure of cancer therapy.To solve the problem,we proposed to develop a novel human serum albumin(HSA)nanoplatform to integrate chemotherapy,photothermal therapy(PTT)and immunotherapy.To this end,we obtained a platinum compound(C5)with significant cytotoxicity in the cisplatin-resistant SKOV-3 cells(SKOV-3/DDP),and then innovatively constructed photosensitizer(indocyanine green(ICG))-encapsulated HSAC5 complex nanoparticles(ICG@HSA-C5 NPs).The ICG@HSA-C5 NPs exhibited excellent photothermal performances in vitro and in vivo.Importantly,the in vivo results revealed that HSA enhanced the antitumor effect of C5 and that the combination of chemotherapy and PTT could significantly inhibit cisplatin-resistant tumor growth and improved the targeting abilities of C5 and ICG,and reduced their side effects.We also confirmed that ICG@HSA-C5 NPs killed the SKOV-3/DDP cells via gasdermin E(GSDME)-mediated pyroptosis and pyroptosis-induced immune responses,thereby synergistically leading to the death of the SKOV-3/DDP cells.展开更多
To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(II...To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.展开更多
For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in...For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.展开更多
基金financially supported by the Natural Science Foundation of China(No.22077021)the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003)。
文摘Cisplatin resistance is the main cause for the failure of cancer therapy.To solve the problem,we proposed to develop a novel human serum albumin(HSA)nanoplatform to integrate chemotherapy,photothermal therapy(PTT)and immunotherapy.To this end,we obtained a platinum compound(C5)with significant cytotoxicity in the cisplatin-resistant SKOV-3 cells(SKOV-3/DDP),and then innovatively constructed photosensitizer(indocyanine green(ICG))-encapsulated HSAC5 complex nanoparticles(ICG@HSA-C5 NPs).The ICG@HSA-C5 NPs exhibited excellent photothermal performances in vitro and in vivo.Importantly,the in vivo results revealed that HSA enhanced the antitumor effect of C5 and that the combination of chemotherapy and PTT could significantly inhibit cisplatin-resistant tumor growth and improved the targeting abilities of C5 and ICG,and reduced their side effects.We also confirmed that ICG@HSA-C5 NPs killed the SKOV-3/DDP cells via gasdermin E(GSDME)-mediated pyroptosis and pyroptosis-induced immune responses,thereby synergistically leading to the death of the SKOV-3/DDP cells.
基金supported by the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003)the National Natural Science Foundation of China(No.22077021).
文摘To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.
基金supported by the Natural Science Foundation of China(No.22077021)the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003).
文摘For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.
