The occurrence of acquired resistance to cisplatin(DDP)that induces the toxic drug effects has always been a huge challenge and urgently needs to be resolved in the cancer treatment.The combination of anticancer drugs...The occurrence of acquired resistance to cisplatin(DDP)that induces the toxic drug effects has always been a huge challenge and urgently needs to be resolved in the cancer treatment.The combination of anticancer drugs with different mechanisms can remarkably improve the chemotherapeutic efficiency.Given that glutathione(GSH)plays as the driving factors in the resistance of DDP,here we have firstly proposed a“three birds,one stone”based nanoplatform to achieve triple synergetic effects simultaneously addressing DDP resistance in non-small cell lung cancer(NSCLC).Specifically,we initially designed and synthesized a DDP prodrug[Pt(Ⅳ)]bridged silsesquioxane precursor(Pt-Si).Then Pt-Si and bis[3-(triethoxysilyl)propyl]diselenide(BTESe PD)were integrated into the framework of mesoporous organosilica nanoparticles(MONs)to obtain a nanocarrier MONPt/Se.After loading with norcantharidin(NCTD)and modifying with the aptamer AS1411 based G-quadruplex(Apt),the Apt@NCTD@MONPt/Seexhibit impressive tumor homing capability.Once being endocytosed,(Ⅰ)the diselenide and-O-Pt(Ⅳ)-O-rich scaffold can be reduced by the excessive GSH,followed by(Ⅱ)breaking the redox homeostasis via GSH depletion and precise release of the DDP.Next,the encapsulated NCTD is also released along with the degradation of the nanocarriers thereby(Ⅲ)achieving the GSH depletion and synergistic anti-tumor effect of NCTD and DDP.Taken together,we believe this“one stone,three birds”strategy may be a promising paradigm to conquer drug resistance for clinical care.展开更多
基金supported by the National Key R&D Program of China(No.2020YFA0709900)the Excellent Postdoctoral Program of Jiangsu Province(No.2022ZB803)+2 种基金National Natural Science Foundation of China(No.82273162)the major science and technology program of Nanjing(No.202305027)the Open Program of NHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine(No.KF202203)。
文摘The occurrence of acquired resistance to cisplatin(DDP)that induces the toxic drug effects has always been a huge challenge and urgently needs to be resolved in the cancer treatment.The combination of anticancer drugs with different mechanisms can remarkably improve the chemotherapeutic efficiency.Given that glutathione(GSH)plays as the driving factors in the resistance of DDP,here we have firstly proposed a“three birds,one stone”based nanoplatform to achieve triple synergetic effects simultaneously addressing DDP resistance in non-small cell lung cancer(NSCLC).Specifically,we initially designed and synthesized a DDP prodrug[Pt(Ⅳ)]bridged silsesquioxane precursor(Pt-Si).Then Pt-Si and bis[3-(triethoxysilyl)propyl]diselenide(BTESe PD)were integrated into the framework of mesoporous organosilica nanoparticles(MONs)to obtain a nanocarrier MONPt/Se.After loading with norcantharidin(NCTD)and modifying with the aptamer AS1411 based G-quadruplex(Apt),the Apt@NCTD@MONPt/Seexhibit impressive tumor homing capability.Once being endocytosed,(Ⅰ)the diselenide and-O-Pt(Ⅳ)-O-rich scaffold can be reduced by the excessive GSH,followed by(Ⅱ)breaking the redox homeostasis via GSH depletion and precise release of the DDP.Next,the encapsulated NCTD is also released along with the degradation of the nanocarriers thereby(Ⅲ)achieving the GSH depletion and synergistic anti-tumor effect of NCTD and DDP.Taken together,we believe this“one stone,three birds”strategy may be a promising paradigm to conquer drug resistance for clinical care.
