Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20-50 nm) and M40 (20-50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging.

Theranostic nanosystems are emerging as a promising approach for controlled drug delivery, diagnosis and multimodal therapeutics. Herein, a multifunctional theranostic nanoplatform is reported for photothermal-chemo combination therapy functioned with magnetic and thermal imaging. Hyaluronic acid (HA) coated Fe3O4@polydopamine nanoparticles equipped with redox-sensitive disulfide linkers have been subsequently deposited with an anticancer drug, doxorubicin (DOX) (termed as FPCH-DOX NPs). These nanocomposites possess an average diameter of 120 nm, a saturation magnetization of 28.5 emu g-1, DOX loading capacity of 7.13% and a transverse relaxation rate of 171.76 mM-1 s-1. The drug release could be triggered by pH, glutathione (GSH) concentration and light irradiation. Prussian blue staining and confocal microscopy demonstrate that these nanoplatforms have improved biocompatibility and cellular uptake in CD44-positive HeLa cell lines rather than in CD44-negative NIH 3T3 normal cell lines. In vitro evaluations demonstrate that the combination therapy of FPCH-DOX NPs lowers the cell viability to 16.2%, less than that of individual chemotherapy (55.3%) or PTT (52.1%). In vivo MRI indicates that the tumor accumulation of FPCH-DOX NPs provides enhanced MRI contrast, and in vivo thermal imaging verified their localized photothermal conversion effect in tumor tissues. Importantly, FPCH-DOX NPs present remarkable anti-tumor efficacy by photothermal-chemo combination therapy. H&E and Ki67 staining tests show obvious necrosis and weak cell proliferation at the region of the tumor. Thus, FPCH-DOX NPs are promising multifunctional nanoplatforms for highly effective cancer theranostics.

Folic acid-modified Prussian blue/polydopamine nanoparticles as an MRI agent for use in targeted chemo/photothermal therapy.

Fabricating multifunctional theranostic nanoparticles is highly pursued but still challenging for effective cancer treatment. Herein is reported a new theranostic nanoagent as both an MRI and targeted chemo/photothermal therapeutic agent. Prussian blue nanoparticles (PB) were first decorated with polydopamine (PDA), then conjugated with polyethylene glycol (PEG) and folic acid (FA), and finally loaded with doxorubicin (DOX) (denoted as PB@PDA@PEG-FA-DOX). The nanoagent was estimated to have an average size of 40 nm with a DOX-loading capacity of 36%, photothermal conversion efficiency of 45.7% and a transverse relaxation rate of 0.366 mM-1 s-1. In vitro release investigations showed a dual-responsive release by a mild acid and near-infrared (NIR) laser irradiation. PB@PDA@PEG-FA illustrated negligible cytotoxicity against the HL-7702 cell line and 38.2% cell viability under NIR against the HeLa cell line. PB@PDA@PEG-FA-DOX exhibited 45.2% cell viability. In contrast, the cell viability of PB@PDA@PEG-FA-DOX was dramatically decreased to 18.4% under NIR. Exclusive of folic acid, PB@PDA@PEG-DOX demonstrated 40.5% cell viability. These results demonstrated the potential of the nanoagent for integrated photothermal therapy (PTT) and chemotherapy, also embracing the FA targeting effect. In vivo MRI confirmed the effective nanoparticle accumulation, while infrared thermal images revealed the dramatically increased temperature under NIR at a tumor site. In vivo combination treatment-induced tumors were nearly completely destroyed without significant body weight loss after 14 days. H&E and Ki67 staining indicated remarkable necrosis and weak cell proliferation in the tumor area. Histologic examination revealed a lower toxicity in the vital organs. Therefore, this combination of chemo/photothermal therapy could provide an efficient route for cancer treatment.