Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)...Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)show many advantages in TNBC treatment,and their combination with chemotherapy can achieve synergistic therapeutic effects.In the present study,a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane(LPHM)and dendritic large pore mesoporous silicon nanoparticles(DLMSNs).A near infrared(NIR)fluorescent dye IR780 and a chemotherapeutic drug doxorubicin(DOX)were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780(DDI)nanoparticles(NPs),followed by camouflage with LPHM to obtain LPHM@DDI NPs.Through the mediation of LPHM,LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo.Upon NIR laser irradiation,LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells,and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis.These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy.Altogether,this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.展开更多
Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous...Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.展开更多
基金the National Natural Science Foundation of China(Nos.81972903,12074284 and 81803101)the Natural Science Foundation of Tianjin City of China(Nos.18JCZDJC33400 and 19JCQNJC12300)the Excellent Talent Project of Tianjin Medical University.
文摘Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)show many advantages in TNBC treatment,and their combination with chemotherapy can achieve synergistic therapeutic effects.In the present study,a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane(LPHM)and dendritic large pore mesoporous silicon nanoparticles(DLMSNs).A near infrared(NIR)fluorescent dye IR780 and a chemotherapeutic drug doxorubicin(DOX)were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780(DDI)nanoparticles(NPs),followed by camouflage with LPHM to obtain LPHM@DDI NPs.Through the mediation of LPHM,LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo.Upon NIR laser irradiation,LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells,and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis.These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy.Altogether,this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.
基金supported by the National Natural Science Foundation of China(No.12074284)the Natural Science Foundation of Tianjin City,China(No.20JCYBJC00170).
文摘Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.