Nanoplatform Self-Assembly from Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-Immunotherapy.

Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts patients with many limitations, such as complex components, sophisticated construction, and inadequate therapeutic efficacy. In this work, small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants are developed. The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originate from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II fluorescence imaging guided photothermal therapy (PTT) against primary tumors with a high cure rate. More importantly, tumor-associated antigens (TAAs), together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells, are proved to elicit immune responses to some degree. After combination with programmed cell death-1 (PD-1) antibodies, a robust systematic antitumor immunity is generated to restrain both primary and abscopal tumors growth, prolong survival, and prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumors with high efficiency.

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.

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.