MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy.

Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy)3Cl2 and GdCl3, which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd3+, and the singlet oxygen generation of Ru(dcbpy)3Cl2, are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.

MRI-guided dual-responsive anti-tumor nanostructures for synergistic chemo-photothermal therapy and chemodynamic therapy.

Image-guided stimulus-responsive theranostics are beneficial for identifying malignant lesions and integrating multiple cell-killing mechanisms to enhance tumor cell clearance. Herein, an intelligent dual-responsive nanostructure (HSPMH-DOX) was developed for magnetic resonance imaging (MRI)-guided synergistic chemo-photothermal therapy (PTT) and chemodynamic therapy (CDT). The core-shell nanostructure was synthesized by layering polydopamine (PDA), manganese oxide (MnO2), and hyaluronic acid (HA) onto drug-loaded hollow mesoporous silica nanoparticles (HS). The constructed nanoagent has both endogenous and external dual responses. The tumor microenvironment (pH/GSH) can trigger the degradation of gatekeeper (MnO2 and PDA), resulting in the release of anti-tumor drugs, whereas external near-infrared light irradiation can accelerate the degradation process and generate local overheating, resulting in PTT. Notably, MnO2 can not only consume intracellular GSH to enhance CDT but also release Mn2+ for precise localization of tumor tissues using MRI. Both in vitro and in vivo experiments showed that the prepared dual-response nanoagent satisfied biocompatibility, targeting, and the great efficiency of MRI-guided combined therapy. In animal models, combining chemo-PTT and CDT can eradicate tumors in less than two weeks. This work could pave the way for a wide range of stimulus-responsive synergistic theranostic applications, including MRI, chemo-photothermal therapy, and chemodynmic therapy. STATEMENT OF SIGNIFICANCE: Low bioavailability and severe side effects remain the major limitations of conventional cancer chemotherapy. Image-guided combination therapy can alleviate these problems and improve tumor-specific therapy. In the present study, the anticancer drug doxorubicin was encapsulated in a core-shell hollow mesoporous silica nanostructure (HSPMH-DOX), enabling MRI-guided targeted release under both endogenous and external dual stimuli. Moreover, the photothermal and nanoenzymatic effects of nanomedicine can cause local overheating in the tumor and amplify the intracellular CDT effect, accelerating tumor eradication. Systematic evaluations in vitro and in vivo confirmed that nanomedicine enables highly effective MRI-guided synergistic chemo-photothermal and chemodynamic therapy. This work offers a promising therapeutic strategy for precise anti-tumor applications.

Magnetic vortex nanoring coated with gadolinium oxide for highly enhanced T1-T2 dual-modality magnetic resonance imaging-guided magnetic hyperthermia cancer ablation.

Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe3O4 @Gd2O3, abbreviated as VNFG) was firstly designed and prepared for highly enhanced T1-T2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG's biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.

NIR/MRI-Guided Oxygen-Independent Carrier-Free Anti-Tumor Nano-Theranostics.

Imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer treatment are beneficial for precise localization of the malignant lesions and combination of multiple cell killing mechanisms in eradicating stubborn thermal-resistant cancer cells. However, overcoming the adverse impact of tumor hypoxia on PDT efficacy remains a challenge. Here, carrier-free nano-theranostic agents are developed (AIBME@IR780-APM NPs) for magnetic resonance imaging (MRI)-guided synergistic PTT/thermodynamic therapy (TDT). Two IR780 derivatives are synthesized as the subject of nanomedicine to confer the advantages for the nanomedicine, which are by feat of amphiphilic IR780-PEG to enhance the sterical stability and reduce the risk from reticuloendothelial system uptake, and IR780-ATU to chelate Mn2+ for T1 -weighted MRI. Dimethyl 2,2'-azobis(2-methylpropionate) (AIBME), acting as thermally decomposable radical initiators, are further introduced into nanosystems with the purpose of generating highly cytotoxic alkyl radicals upon PTT launched by IR780 under 808 nm laser irradiation. Therefore, the sequentially generated heat and alkyl radicals synergistically induce cell death via synergistic PTT/TDT, ignoring tumor hypoxia. Moreover, these carrier-free nano-theranostic agents present satisfactory biocompatibility, which could be employed as a powerful weapon to hit hypoxic tumors via MRI-guided oxygen-independent PTT and photonic TDT.

Multifunctional Hf/Mn-TCPP Metal-Organic Framework Nanoparticles for Triple-Modality Imaging-Guided PTT/RT Synergistic Cancer Therapy.

BACKGROUND: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications. MATERIALS AND METHODS: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed "all-in-one" FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent. RESULTS: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3-5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs. CONCLUSION: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.