Localized NIR-II photo-immunotherapy through the combination of photothermal ablation and in situ generated interleukin-12 cytokine for efficiently eliminating primary and abscopal tumors.

Recently, photothermal therapy (PTT) in the second near-infrared (NIR-II) biowindow has emerged as a promising treatment modality; however, its therapeutic outcomes are still limited by heterogeneous heat distribution and insufficient control of metastatic lesions. Tremendous efforts have been made to overcome the PTT's shortcomings by combining PTT with immunotherapy, but unfortunately current strategies still suffer from low response rates, primary/acquired resistance or severe immune-related adverse events. Herein, a novel photothermal agent and gene co-delivery nanoparticle (CSP), with CuS inside the SiO2 pore channels and PDMAEMA polycation on the outside of SiO2 surface, is explored for tumor localized NIR-II PTT and in situ immunotherapy through local generation of IL-12 cytokine. The resulting CSP integrated with the plasmid encoding IL-12 gene (CSP@IL-12) exhibited good gene transfection efficiency, outstanding NIR-II PTT effect and excellent therapeutic outcomes both in vitro and in vivo. Meanwhile, such an in situ joint therapy modality could significantly induce systemic immune responses including promoting DC maturation, CD8+ T cell proliferation and infiltration to efficiently eliminate possible metastatic lesions through abscopal effects. Hence, this creative combinational strategy of NIR-II PTT and IL-12 cytokine therapy might provide a more efficient, controllable and safer alternative strategy for future photo-immunotherapy.

Facile phase transfer of hydrophobic Fe3O4@Cu2-xS nanoparticles by red blood cell membrane for MRI and phototherapy in the second near-infrared window.

The development of nanotheranostic agents integrating diagnosis and therapy has gained tremendous attention in the past few decades, but many of them are inherently hydrophobic and need complicated phase-transfer and tedious surface modifications. This work proposed a facile method of transferring hydrophobic Fe3O4@Cu2-xS nanoparticles from oil to water by using red blood cell membrane to create theranostic nanobeads for T2-weighted MRI and second near-infrared photothermal ablation. The obtained nanoplatform, namely SCS@RBCM, showed a core-shell structure with the inner core densely packed with Fe3O4@Cu2-xS nanoclusters and the surface coated with a layer of RBCM. SCS@RBCM displayed a stable nanostructure, high NIR II light absorption and photothermal conversion ability, T2-weighted MR imaging and magnetic field targeting ability. Meanwhile, the RBCM cloaking endowed SCS with reduced elimination by macrophages. With the navigation of an external magnetic field (MF), the tumor accumulation of SCS@RBCM was dramatically increased, thus achieving good performance of MR imaging and antitumor efficacy through the PTT effect under NIR II irradiation. Therefore, our strategy presents a new and desirable paradigm in the phase-transfer of hydrophobic nanotheranostics for optimizing their biomedical performance.

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.