Superparamagnetic iron oxide (SPIO) nanoparticles have been extensively employed for theranostic applications due to their good biocompatibility and excellent magnetic resonance imaging (MRI) properties. However, these particles typically require surface modification due to their hydrophobic surfaces caused by the oil-phase surfactants used in the fabrication and thus, the drug loading on their surface is usually limited. Here, we provided a novel and facile approach to conveniently perform surface modification of SPIO while simultaneously loading a large amount of drug. By synthesizing an amphiphilic irinotecan-based compound with a hydrophobic tail enabling insertion into the SPIO assembly, an excellent SPIO-based theranostic nanomedicine (SPIO@IR) was produced. SPIO@IR not only extensively improved the drug efficacy, but also allowed visualization by MRI in biological systems.

Despite its great promise in non-invasive treatment of cancers, magnetic resonance-guided focused ultrasound surgery (MRgFUS) is currently limited by the insensitivity of magnetic resonance imaging (MRI) for visualization of small tumors, low efficiency of in vivo ultrasonic energy deposition, and damage to surrounding tissues. We hereby report the development of an active targeting nano-sized theranostic superparamagnetic iron oxide (SPIO) platform for significantly increasing the imaging sensitivity and energy deposition efficiency using a clinical MRgFUS system. The surfaces of these PEGylated SPIO nanoparticles (NPs) were decorated with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies (mAb) for targeted delivery to lung cancer with EGFR overexpression. The potential of these targeted nano-theranostic agents for MRI and MRgFUS ablation was evaluated in vitro and in vivo in a rat xenograft model of human lung cancer (H460). Compared with nontargeting PEGylated SPIO NPs, the anti-EGFR mAb targeted PEGylated SPIO NPs demonstrated better targeting capability to H460 tumor cells and greatly improved the MRI contrast at the tumor site. Meanwhile, this study showed that the targeting NPs, as synergistic agents, could significantly enhance the efficiency for in vivo ultrasonic energy deposition in MRgFUS. Moreover, we demonstrated that a series of MR methods including T2-weighted image (T2WI), T1-weighted image (T1WI), diffusion-weighted imaging (DWI) and contrast-enhanced T1WI imaging, could be utilized to noninvasively and conveniently monitor the therapeutic efficacy in rat models by MRgFUS.

Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment.

Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags' T₂ contrast enhancement and transverse relaxation rate R₂, depending on the drug loading level. The T₂ enhancement and R₂ could be recovered once the drug was released upon PolyMags' disassembly. T₂ & T₂* MRI and diffusion-weighted imaging (DWI) were utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. We visualized the in vivo drug release pattern based on such tunable MRI capability via monitoring the changes in T₂-weighted images, T₂ & T₂* maps and R₂ & R₂* values. Interestingly, the PolyMags possessed excellent photothermal effect, which could be further enhanced upon DOX loading. The PolyMags were highly efficacious to treat breast tumors on xenograft model with tumor-targeted photothermal-and chemo-therapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image-guided drug delivery & release applications toward precision cancer therapy.

Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality. Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents, so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies. FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.

Four different high-entropy spinel oxide ferrite (HESO) electrode materials containing 5-6 distinct metals were synthesized by a simple, rapid combustion synthesis process and evaluated as conversion anode materials in lithium half-cells. All showed markedly superior electrochemical performance compared to conventional spinel ferrites such as Fe3O4 and MgFe2O4, having capacities that could be maintained above 600 mAh g-1 for 150 cycles, in most cases. X-ray absorption spectroscopy (XAS) results on pristine, discharged, and charged electrodes show that Fe, Co, Ni, and Cu are reduced to the elemental state during the first discharge (lithiation), while Mn is only slightly reduced. Upon recharge (delithiation), Fe is reoxidized to an average oxidation state of about 2.6+, while Co, Ni, and Cu are not reoxidized. The ability of Fe to be oxidized past 2+ accounts for the high capacities observed in these materials, while the presence of metallic elements after the initial lithiation provides an electronically conductive network that aids in charge transfer.

Four different high-entropy spinel oxide ferrite (HESO) electrode materials containing 5-6 distinct metals were synthesized by a simple, rapid combustion synthesis process and evaluated as conversion anode materials in lithium half-cells. All showed markedly superior electrochemical performance compared to conventional spinel ferrites such as Fe₃O₄ and MgFe₂O₄, having capacities that could be maintained above 600 mAh g^-1 for 150 cycles, in most cases. X-ray absorption spectroscopy (XAS) results on pristine, discharged, and charged electrodes show that Fe, Co, Ni, and Cu are reduced to the elemental state during the first discharge (lithiation), while Mn is only slightly reduced. Upon recharge (delithiation), Fe is reoxidized to an average oxidation state of about 2.6+, while Co, Ni, and Cu are not reoxidized. The ability of Fe to be oxidized past 2+ accounts for the high capacities observed in these materials, while the presence of metallic elements after the initial lithiation provides an electronically conductive network that aids in charge transfer.

The efficacy of therapeutics for brain tumors is seriously hampered by multiple barriers to drug delivery, including severe destabilizing effects in the blood circulation, the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB), and limited tumor uptake. Here, a sequential targeting in crosslinking (STICK) nanodelivery strategy is presented to circumvent these important physiological barriers to improve drug delivery to brain tumors. STICK nanoparticles (STICK-NPs) can sequentially target BBB/BBTB and brain tumor cells with surface maltobionic acid (MA) and 4-carboxyphenylboronic acid (CBA), respectively, and simultaneously enhance nanoparticle stability with pH-responsive crosslinkages formed by MA and CBA in situ. STICK-NPs exhibit prolonged circulation time (17-fold higher area under curve) than the free agent, allowing increased opportunities to transpass the BBB/BBTB via glucose-transporter-mediated transcytosis by MA. The tumor acidic environment then triggers the transformation of the STICK-NPs into smaller nanoparticles and reveals a secondary CBA targeting moiety for deep tumor penetration and enhanced uptake in tumor cells. STICK-NPs significantly inhibit tumor growth and prolong the survival time with limited toxicity in mice with aggressive and chemoresistant diffuse intrinsic pontine glioma. This formulation tackles multiple physiological barriers on-demand with a simple and smart STICK design. Therefore, these features allow STICK-NPs to unleash the potential of brain tumor therapeutics to improve their treatment efficacy.

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and fewer interactions with the surroundings as compared with those of fluorescence-based Förster resonance energy transfer. However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T₁-based MRET probes. Here we report a new two-way magnetic resonance tuning (TMRET) nanoprobe with dually activatable T₁ and T₂ magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging. This integrated platform achieves a substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by TMRET in combination with dual-contrast enhanced subtraction imaging provides new opportunities for molecular diagnostics and image-guided biomedical applications.

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and fewer interactions with the surroundings as compared with those of fluorescence-based Förster resonance energy transfer. However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T₁-based MRET probes. Here we report a new two-way magnetic resonance tuning (TMRET) nanoprobe with dually activatable T₁ and T₂ magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging. This integrated platform achieves a substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by TMRET in combination with dual-contrast enhanced subtraction imaging provides new opportunities for molecular diagnostics and image-guided biomedical applications.