Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn
2+
-coordinated doxorubicin (DOX)-loaded poly(lactic-
co
-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn
2+
ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn
2+
-PDA@DOX/PLGA nanoparticles. In our system, Mn
2+
-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn
2+
could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn
2+
-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.
Imaging-guided
diagnosis and therapy has been highlighted in the
area of nanomedicines. However, integrating multiple functions with
high performance in one theranostic (“all-in-one”) still
presents considerable challenges. Here, “all-in-one”
nanoparticles with drug-loading capacity, catalase-mimetic activity,
photoacoustic (PA) imaging ability and photothermal properties were
prepared by decorating Au nanoparticles on doxorubicin (DOX) encapsulated
poly(lactic-co-glycolic acid) (PLGA) vehicle. The
results revealed that the as-prepared Au-PLGA hybrid nanoparticles
possessed high photothermal conversion efficiency of up to approximately
69.0%, meanwhile their strong acoustic generation endowed them with
efficient PA signal sensing for cancer diagnosis. On an 808 nm laser
irradiation, the O2 generation, DOX release profile and
reactive oxygen species (ROS) level were all improved, which were
beneficial to relieving tumor hypoxia and enhanced the cancer chemo/PTT
combined therapy. Overall, the multifunctional Au-PLGA hybrid nanoparticles
with these integrated advantages shows promise in PA imaging-guided
diagnosis and synergistic tumor ablation.
Ovarian cancer is known for its highest mortality rate in gynecological malignancy. Previous studies demonstrated that thymoquinone (TQ), a bioactive compound isolated from Nigella sativa L., is a potent anti-ovarian cancer agent, which inhibit tumor growth by modulating apoptotic activity. In this study, we found that the effect of chemotherapy on ovarian cancer cells in vitro varies by race/ethnicity. HO-8910 was established from Chinese patient with ovarian serous carcinoma. The results showed that HO-8910 displayed higher resistance to platinum than SKOV3. And further cell variability assay indicated that TQ exhibited dramatically inhibitory activity on HO-8910 and SKOV3. However, apoptosis and cell cycle analysis suggested TQ had multiple mechanisms for its cytotoxic effect. As for HO-8910, TQ could modulated expression level of several pivotal factors involving autophagy, including PI3K, ATG-7, Bectlin-1 and p62, but has little effect on p53, PARP and caspase-3, and no effect on Bax. Our results sustained that TQ was a promising anti-ovarian cancer candidate and its potential application in Chinese patients, even Asian patients , treatment in clinic.
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