Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis

The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune cells.To solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor site.Upon irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ICD.Moreover,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic tumors.In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.

Silica-based nanoarchitecture for an optimal combination of photothermal and chemodynamic therapy functions of Cu2–xS cores with red emitting carbon dots

This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities,in addition to luminescence.The activity of the silica nanoparticles is derived from their plasmonic properties,which are a result of infusing the silica nanoparticles with multiple Cu2-xS cores.This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant.The key factors that enable the internal incorporation of the Cu2-xS cores and the external deposition of red-emitting carbon dots are identified.The Cu2-xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy,which are essential for photothermal and chemodynamic activities.The silica nanoparticles’small size(no more than 70 nm)and high colloidal stability are prerequisites for their cell internalization.The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques.The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity,and the mechanisms of cell death are evaluated using an apoptotic assay.The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared(1064 nm)irradiation.