RESUMEN
Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p-toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.
Asunto(s)
Retículo Endoplásmico , Inmunoterapia , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Animales , Ratones , Femenino , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Nanopartículas/química , Retículo Endoplásmico/metabolismo , Humanos , Hemo-Oxigenasa 1/metabolismo , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Plata/química , Plata/farmacología , Porfirinas/química , Porfirinas/farmacologíaRESUMEN
OBJECTIVE: To study the distribution of allergens in our district and the correlation between skin prick test with antigen and nasal provoking test in patients with allergic rhinitis. METHOD: A total of 1400 cases with allergic symptoms and signs underwent skin prick test with standardized aero antigens provoking by Allergo Phamar Company. The patients allergic to Dermatophagoides with different scale of the skin prick test were taken nasal provoking test in order to evaluate the correlation between skin prick test and nasal provoking test. RESULT: One thousand and eighty-eight (78%) cases showed a positive result in skin prick test. The percent of patients with positive skin prick test were as follows: 462 cases of Dermatophagoides pteronyssinus, 428 cases of Dermatophagoides farinae. Positive perennial aero antigens were 52.2% (568), positive seasonal aero antigens were 35.7% (388). All the patients of the scale of skin prick test was +++ and ++++ were positive. There are 29 patients were positive with nasal provoking test which the scale of skin prick test was ++. There are 21 patients were positive with nasal provoking test, which the scale of skin prick test was +. CONCLUSION: The correlation between skin test with antigens and nasal provoking test in patients whose positive scale were +++ and ++++. There are false positive in the patients whose positive scale were + and ++. The specific immunotherapy should consider the scale of the skin prick test and eliminate the false positive before the therapy.