Search

Currently, multimodal synergistic nanoplatform emerges as an important cancer therapy paradigm, however, multimodal synergistic theranostic nanoplatform remains to be developed. Herein, using the mouse model of breast cancer, a versatile multimodal synergistic theranostic nanoplatform is rationally designed and synthesized for enhancing chemodynamic therapy (CDT), overcoming immunosuppression within tumor microenvironment, and inhibiting metastasis as well as tracking tumor. To fulfill our design, a composite Fe/Mn magnetic nanoparticle is first synthesized by loading with Fe 3 O 4 and BMS-202 (PD-L1 inhibitor) within a poly(lactide-co-glycolide)-based nanoparticle core, which are further modified with in situ synthesis of MnO 2 layer. Then, the composite metal-organic nanoparticle is coated with two targeting moieties hyaluronic acid (HA) and AMD3100 (CXCR4 antagonist), respectively, to achieve the multimodal synergistic theranostic nanoplatform (FMN-BMS@HA+AMD). With surface targeting modification, FMN-BMS@HA+AMD exhibits enhanced tumor accumulation, where it effectively consumes endogenous glutathione to generate Mn2+ allowing for the enhanced CDT effect, alleviates tumor hypoxia by O 2 generation and reverses the tumor immunosuppression. FMN-BMS@HA+AMD blocks CXCR4 receptor on cancer cells, thus suppressing the CXCR4-mediated cancer metastasis and invasion. Additionally, FMN-BMS@HA+AMD would synchronously be achieving tumor tracking by T 1 -T 2 dual-mode magnetic resonance imaging. Collectively, this strategy holds a novel multimodal synergistic theranostics for effective cancer management. [Display omitted] • The multimodal synergistic therapy exerts remarkable synergistic effects ("1 + 1 >2″). • The multimodal synergistic inhibits tumor growth and metastasis, and boosts immune effects. • Encapsulated Fe 3 O 4 and generated Mn2+ would synchronously enhance magnetic resonance imaging-mediated tumor tracking. [ABSTRACT FROM AUTHOR]

The probe plays a pivotal role in the early diagnosis of tumor, especially tumor microenvironment (TME)-responsive probe, which could exploit differences between tumor and normal tissue to achieve better signal-to-noise ratio. In view of overexpressed glutathione (GSH) in microenvironment considered as one of the important characteristics of tumor distinct from normal tissue, we constructed a GSH activated near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modal probe (Probe-GSH) based on the hybrid of xanthene-based hemicyanines and dicyanoisophorone. The activated Probe-GSH could exhibit 8-fold PA signal/10-fold NIRF intensity enhancement. Besides, compared with the existing xanthene-based hemicyanines (XBH), Probe-GSH possessed longer absorbance/emission wavelength and larger Stokes shift. More importantly, Probe-GSH has been successfully applied to the image of 4T1-bearing tumor mice under NIRF and PA dual modality. [Display omitted] • Compared with the reported xanthene-based hemicyanines, Probe-GSH possess longer the absorbance/ emission wavelength. • Compared with the reported xanthene-based hemicyanines, Probe-GSH has larger Stokes shift. • Probe-GSH was capable for imaging of tumor mouse under NIRF and PA dual modality image. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, characterized by high heterogeneity, strong invasiveness, poor prognosis, and a low survival rate. A broad range of nanoparticles have been recently developed as drug delivery systems for GBM therapy owing to their inherent size effect and ability to cross the blood–brain barrier (BBB). Lipid-based nanoparticles (LBNPs), such as liposomes, solid lipid NPs (SLNs), and nano-structured lipid carriers (NLCs), have emerged as the most promising drug delivery system for the treatment of GBM because of their unique size, surface modification possibilities, and proven bio-safety. In this review, the main challenges of the current clinical treatment of GBM and the strategies on how novel LBNPs overcome them were explored. The application and progress of LBNP-based drug delivery systems in GBM chemotherapy, immunotherapy, and gene therapy in recent years were systematically reviewed, and the prospect of LBNPs for GBM treatment was discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials. [Display omitted] • Man/PPS-SPIONs exhibit tumor accumulation facilitated by an external magnetic field. • PPS and iron-based nanocarriers synergistically induce M1 polarization of TAMs. • The "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway works for M1 polarization of TAMs. • Man/PPS-SPIONs created a favorable condition for celastrol-based therapy. • Man/PPS-SPIONs overcomes the limitations of celastrol in anti-tumor therapy. [ABSTRACT FROM AUTHOR]