| Breast cancer and its metastasis have become a devastating disease and the main cause of cancer-related deaths in women.The early symptoms of primary tumor are usually not obvious,and breast cancer metastasis is often occurs before diagnosis of the primary tumor,during the course of treatment even several years after treatment.Hence,the early diagnosis and precise therapy of breast cancer have become an urgent challenge in the field of medical research.On the one hand,the imaging examination is of important basis for early diagnosis of breast cancer and the choice of individualized treatment strategy.Although traditional imaging technologies including ultrasound(US),MR,CT,optical imaging and SPECT have been widely applied in clinic,the inherent limitations of each imaging mode cannot be ignored.On the other hand,surgical resection,chemotherapy and radiotherapy remain the mainstream forms of treatment for breast cancer,but outcome improvements and survival rates are still unsatisfactory due to incomplete resection and obvious systemic toxicity of aforementioned traditional treatment methods.Especially,some metastatic tumors are small in sizes and hidden in locations,which are difficult to be completely eliminated by traditional surgical resection.In this paper,therefore,two nano-sized theranostic agents were designed,aiming at exploring a real-time and effective theranostic strategy for breast cancer and metastatic tumor.By virtue of these nanoagents,more detailed molecular imaging information of breast cancer and its metastasis can be obtained,and tumors can be eliminated simultaneously with higher efficacy,providing a novel strategy for precise diagnosis and therapy of breast cancer.The main contents and conclusions of study in this paper are as follows:(1)In the first part,a NIR light-controllable and HER2-targeting drug delivery nanoagent(PFH-PTX@PLGA/SPIO-Her NPs)was successfully fabricated by using double emulsion method.The carboxyl-modified carboxyl-modified mPEGylated poly(lactic-co-glycolic acid)(PLGA-mPEG-COOH)was used as the carrier of the nanoagent,loading superparamagnetic iron oxide nanoparticles(SPIO),perfluorohexane(PFH)and paclitaxel(PTX).Then,monoclonal antibody Herceptin(HER)was modified onto the PLGA-mPEG-COOH carrier surface using carbodiimide method.The developed nanoagent was uniform in size and stable in shape.Herceptin on the surface of spherical nanoagent endowed the nanoagent a HER2-targeting property,which significantly promote the accumulation of nanoagent in tumor.SPIO was used as a photoacoustic(PA)imaging agent to guide the following therapy of breast cancer.Upon NIR irradiation,SPIO also showed a good photothermal conversion efficiency(20.19%),which can be used for photothermal ablation of primary breast cancer.The thermal effect induced by NIR light can trigger the optical droplet vaporization(ODV)of phase change material(PFH)in the nanoagent,thus generating a large number of PFH microbubbles and achieving enhanced US imaging.The process of PFH ODV also promoted the effective release of loaded PTX in the nanoagent,which significantly reduced systemic side effects of chemotherapy drug.The results in the first part of study show that the light-responsive and HER2-targeting drug delivery nanoagent(PFH-PTX@PLGA/SPIO-Her NPs)realizes the combination of PA/US dual-mode imaging guided photothermal therapy(PTT),NIR light-responsive drug release,synergistically enhancing the PTT/chemo therapeutic efficacy of breast cancer.(2)Based on the conclusion of the first part,the early diagnosis and therapy for metastatic breast cancer was further studied in the second part.A magnetic-responsive and immunostimulatory nanoagent(MINPs)was constructed by using double emulsion method.The mPEGylated poly(lactic-co-glycolic acid)-poly-l-lysine(PLGA-mPEG-PLL)triblock co-polymer was served as the carrier of the MINPs,and SPIO nanoparticles and immunoadjuvant(CpG ODNs)were encapsulated into it.Under external magnetic fields,the MINPs exhibited an obvious magnetic-targeting performance,which can promote the accumulations of SPIO and CpG ODNs into tumor region.The excellent PA imaging and MRI capabilities of the MINPs enabled PA/MR bimodal imaging in vivo.Upon NIR exposure,the primary breast cancer was effectively ablated via photothermal effect of the MINPs,releasing the tumor related antigens.With the help of immunoadjuvant CpG ODNs,the antigen presentation of above tumor related antigens through dendritic cells(DCs)was significantly increased and the activation of CD8+ T cells was effectively stimulated,thereby activating anti-tumor immune responses in vivo and further attacking the residual and metastatic breast cancer cells.This part of study provides a MINPs-based visual photothermally triggered immunotherapy strategy with high specificity,easy operation and good biocompatibility.By virtue of the theranostic strategy,the primary breast tumor can be photothermally ablated,and the distant breast bumor can be inhibited simultaneously,which exhibits a great potential in medical applications of the precise diagnosis and individualized therapy for breast cancer. |
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