Photothermal therapy(PTT)has emerged as a promising cancer therapeutic method.In this study,Arg-Gly-Asp(RGD)peptide-conjugated polydopamine-coated gold nanostars(Au@PDA-RGD NPs)were prepared for targeting PTT of hepat...Photothermal therapy(PTT)has emerged as a promising cancer therapeutic method.In this study,Arg-Gly-Asp(RGD)peptide-conjugated polydopamine-coated gold nanostars(Au@PDA-RGD NPs)were prepared for targeting PTT of hepatocellular carcinoma(HCC).A polydopamine(PDA)shell was coated on the surface of gold nanostars by the oxidative self-polymerization of dopamine(termed as Au@PDA NPs).Au@PDA NPs were further functionalized with polyethylene glycol and RGD peptide to improve biocompatibility as well as selectivity toward the HCC cells.Au@PDARGD NPs showed an intense absorption at 822 nm,which makes them suitable for near-infraredexcited PTT.Our results indicated that the Au@PDA-RGD NPs were effective for the PTT therapy of the α_(v)β_(3) integrin receptor-overexpressed HepG2 cells in vitro.Further antitumor mechanism studies showed that the Au@PDA-RGD NPs-based PTT induced human liver cancer cells death via the mitochondrial-lysosomal and autophagy pathways.In vivo experiments showed that Au@PDARGD NPs had excellent tumor treatment efficiency and negligible side effects.Thus,our study showed that Au@PDA-RGD NPs could offer an excellent nanoplatform for PTT of HCC.展开更多
Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To add...Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites.Here,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor elimination.Importantly,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1.In the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and recurrence.Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.展开更多
基金support from National Natural Science Foundation of China(NSFC81602736)China Postdoctoral Science Foundation(2018M632684)+1 种基金Shandong Provincial Natural Science Foundation(ZR2019PH084)Liaocheng People’s Hospital Youth Research Fund(LYQN201935).
文摘Photothermal therapy(PTT)has emerged as a promising cancer therapeutic method.In this study,Arg-Gly-Asp(RGD)peptide-conjugated polydopamine-coated gold nanostars(Au@PDA-RGD NPs)were prepared for targeting PTT of hepatocellular carcinoma(HCC).A polydopamine(PDA)shell was coated on the surface of gold nanostars by the oxidative self-polymerization of dopamine(termed as Au@PDA NPs).Au@PDA NPs were further functionalized with polyethylene glycol and RGD peptide to improve biocompatibility as well as selectivity toward the HCC cells.Au@PDARGD NPs showed an intense absorption at 822 nm,which makes them suitable for near-infraredexcited PTT.Our results indicated that the Au@PDA-RGD NPs were effective for the PTT therapy of the α_(v)β_(3) integrin receptor-overexpressed HepG2 cells in vitro.Further antitumor mechanism studies showed that the Au@PDA-RGD NPs-based PTT induced human liver cancer cells death via the mitochondrial-lysosomal and autophagy pathways.In vivo experiments showed that Au@PDARGD NPs had excellent tumor treatment efficiency and negligible side effects.Thus,our study showed that Au@PDA-RGD NPs could offer an excellent nanoplatform for PTT of HCC.
基金the financial support of the National Natural Science Foundation of China (Nos.81925036 & 81872814)the Science & Technology Major Project of Sichuan Province (No.2018SZDZX0018,China)+2 种基金the Key Research and Development Program of Science and Technology Department of Sichuan Province (No.2020YFS0570,China)111 project (No.b18035,China)the Fundamental Research Funds for the Central Universities (China)。
文摘Photothermal therapy has been intensively investigated for treating cancer in recent years.However,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence.To address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites.Here,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor elimination.Importantly,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1.In the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and recurrence.Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
