Machine Learning Predicting Optimal Preparation of Silica-Coated Gold Nanorods for Photothermal Tumor Ablation.

Gold nanorods (GNRs) coated with silica shells are excellent photothermal agents with high surface functionality and biocompatibility. Understanding the correlation of the coating process with both structure and property of silica-coated GNRs is crucial to their optimizing preparation and performance, as well as tailoring potential applications. Herein, we report a machine learning (ML) prediction of coating silica on GNR with various preparation parameters. A total of 306 sets of silica-coated GNRs altogether were prepared via a sol-gel method, and their structures were characterized to extract a dataset available for eight ML algorithms. Among these algorithms, the eXtreme gradient boosting (XGboost) classification model affords the highest prediction accuracy of over 91%. The derived feature importance scores and relevant decision trees are employed to address the optimal process to prepare well-structured silica-coated GNRs. The high-throughput predictions have been adopted to identify optimal process parameters for the successful preparation of dumbbell-structured silica-coated GNRs, which possess a superior performance to a conventional cylindrical core-shell counterpart. The dumbbell silica-coated GNRs demonstrate an efficient enhanced photothermal performance in vivo and in vitro, validated by both experiments and time domain finite difference calculations. This study epitomizes the potential of ML algorithms combined with experiments in predicting, optimizing, and accelerating the preparation of core-shell inorganic materials and can be extended to other nanomaterial research.

Synchronous enhancement of upconversion and NIR-IIb photoluminescence of rare-earth nanoprobes for theranostics.

This study develops a multifunctional molecular optical nanoprobe (SiO2@Gd2O3: Yb3+/Er3+/Li+@Ce6/MC540) with a unique core-satellite form. The rare-earth doped nanodots with good crystallinity are uniformly embedded on the surface of a hydrophilic silica core, and the nanoprobe can emit near-infrared-IIb (NIR-IIb) luminescence for imaging as well as visible light that perfectly matches the absorption bands of two included photosensitizers under 980 nm irradiation. The optimal NIR-IIb emission and upconversion efficiency are attainable via regulating the doping ratios of Yb3+, Er3+ and Li+ ions. The relevant energy transfer mechanism was addressed theoretically that underpins rare-earth photoluminescence where energy back-transfer and cross relaxation processes play pivotal roles. The nanoprobe can achieve an excellent dual-drive photodynamic treatment performance, verified by singlet oxygen detections and live-dead cells imaging assays, with a synergistic effect. And a brightest NIR-IIb imaging was attained in tumoral site of mouse. The nanoprobe has a high potential to serve as a new type of optical theranostic agent for tumor.

Plasmon-induced double-field-enhanced upconversion nanoprobes with near-infrared resonances for high-sensitivity optical bio-imaging.

High-sensitivity optical imaging can be achieved through improving upconversion photoluminescence (UCPL) efficiency of localized surface plasmon resonance (LSPR)-enhanced excitation and emission. Herein, we report a type of UCPL nanoprobe, Au nanospheres assemblage@Gd2O3:Yb3+/Ln3+(Ln = Er, Ho, Tm), which exhibits emission enhancements from 46- to 96-fold as compared with its Au-free counterparts. The aggregation and interaction among Au nanospheres embedded inside the nanoprobe brings about three characteristic LSPR peaks in visible and near-infrared regions according to simulated and experimental absorption spectra, resulting in both excitation and emission fields simultaneously intensified all through the entire nanoprobe. We addressed a characteristic wavelength dependence on emission amplifications, which could be elucidated by a LSPR-enhanced UCPL mechanism and relevant rate equations that we addressed. The nanoprobe was verified to have a superior capability for optical bio-imaging with a negligible toxicityin vitroandin vivo. This study realizes a synchronous double-field-enhanced upconversion of optical nanoprobein situ, and may gain an insight into its mechanism underlying for LSPR-induced UCPL enhancement.

Nanoassembly and Multiscale Computation of Multifunctional Optical-Magnetic Nanoprobes for Tumor-Targeted Theranostics.

Gold nanorods, mesoporous silica, gadolinia, folic acid, and polyethylene glycol (PEG) derivatives have been investigated due to their own advantages in cancer theranostics. However, it remains a great challenge to assemble these components into a stable unity with the diverse and enhanced functionality for more potential applications. Herein, as inspired by the first-principles calculation, a highly stable and safe all-in-one nanoprobe is fabricated via a novel nanoassembly strategy. Multiscale calculations were performed to address the atomistic bonding of a nanoprobe, heat necrosis of a tumor adjacent to the vasculature, and thermal diffusion in a photothermal circumstance, respectively. The nanoprobe gains an 8-fold increase in magnetic resonance imaging (MRI) relaxivity compared to the clinical gadolinium diethylenetriaminepentaacetate, achieving a significant MRI signal in vivo. Conjugated with folate-PEG, the nanoprobe can be effectively absorbed by tumoral cells, obtaining a vivid two-photon cell imaging. A specific multisite scheme for photothermal therapy of a solid tumor is proposed to improve low photothermal efficacy caused by thermal diffusion in a large tumor, leading to the successful cure of the mice with xenograft tumor sized 10-12 mm. In vitro and in vivo toxicity, long-term excretion data, and the recovery of the treated mice demonstrate that the theranostic nanoprobe possesses good biocompatibility and metabolism efficacy.

Dysprosium-doped iron oxide nanoparticles boosting spin-spin relaxation: a computational and experimental study.

Early diagnosis of diseases by contrast-enhanced magnetic resonance imaging (MRI) using iron oxide superparamagnetic nanoparticles (IOSNPs) has been extensively investigated due to the good biocompatibility of modified IOSNPs. However, the low magnetic sensitivity of IOSNPs still inflicts a certain limitation on their further application. In this study, we employed first-principles calculations based on spin-polarized density functional theory (SDFT) to find the optimal dysprosium-doped scheme for improving the magnetic sensitivity of IOSNPs. Elicited from the optimal doping scheme, we synthesized a sort of ultrasmall γ-iron oxide superparamagnetic nanoparticle by a special phase transfer-coprecipitation method. The appropriately Dy-doped γ-IOSNPs coated with short-chain polyethylene glycol are small in hydrodynamic size and highly dispersed with effectively improved superparamagnetism for enhancing T2-weighted MRI relaxivity, which is well consistent with the SDFT prediction. The measured spin-spin relaxivity r2 is 123.2 s-1 mM-1, nearly double that of the pure γ-IOSNPs (67.8 s-1 mM-1) and substantially surpassing that of both clinically-approved T2 contrast agents Feridex and Resivist. The low dysprosium doping does not induce notable nanotoxicity for IOSNPs, but contributes sufficiently to their high relaxation performance instead, which endows the Dy-doped γ-IOSNPs with high potential as a better T2-weighted MRI contrast medium. Both the method and the nanomagnets reported in this study are expected to promote studies on designing and preparing high-performance MRI contrast agents as well as computational materials.

MRI relaxivity enhancement of gadolinium oxide nanoshells with a controllable shell thickness.

Gadolinium oxide-based core-shelled nanoparticles have recently emerged as novel magnetic resonance imaging contrast agents for high relaxivity and tumor targeting. However, their relaxivity enhancement mechanism has not yet been clearly understood. We prepared highly dispersible and uniform core-shell structured nanoparticles by encapsulating silica spheres (90 nm in diameter) with gadolinium oxide shells of different thicknesses (from 1.5 nm to 20 nm), and proved experimentally that the shell thickness has an inverse effect on relaxivity. The core-shelled nanoparticles are of a larger relaxivity than the commercial contrast agent Gd-DTPA, with an enhancement from 1.8 to 7.3 times. Based on the Solomon-Bloembergen-Morgan theory which is usually adopted for interpreting the relaxation changes of water protons in Gd3+ chelates, we introduced a shielding ansatz of nanoshells and derived a concise formula specifically to correlate the relaxivity of this sort of core-shelled nanoparticles with the shell thickness directly. The formula calculation is well consistent with the experimental results, and the formula can be generally applied to evaluate the relaxation enhancement underlying the high relaxivity of any core-shelled nanoparticle. Furthermore, the core-shelled nanoparticles possess a negligible nanotoxicity according to the in vitro cytotoxicity and in vivo histopathology and hematology assays. The enhanced signals of in vivo tumor-targeted magnetic resonance imaging indicate that the ultrathin gadolinium oxide nanoshells may function as a potential candidate for advanced positive contrast agents in further clinical applications.

Tumor-targeted nanoprobes for enhanced multimodal imaging and synergistic photothermal therapy: core-shell and dumbbell Gd-tailored gold nanorods.

Multifunctional nanoprobes, due to their unique nanocomposite structures, have prominent advantages that combine multimodal imaging of a tumor with photothermal therapy. However, they remain a challenge for constructing nanostructures via conventional approaches due to the peculiar environmental sensitivity of each component. Here, we report the design and synthesis of Gd-based nanoparticle-tailored gold nanorods with distinctive core-shell and dumbbell nanoarchitectures (NAs) by a specific synthesis technology. The prepared NAs possess a tunable particle size of 80-120 nm in length and 50-90 nm in diameter, which are suitable for cellular uptake and passive targeting of a tumor. The formation of two distinct heterostructures and their underlying mechanism were studied through systematic investigations on the controllable synthesis process. The as-prepared nanoprobes possess an ultrahigh longitudinal relaxivity (r1) of 22.69 s-1 mM-1 and thus a significant magnetic resonance imaging signal enhancement has been observed in mice tumors. The NAs, especially the dumbbell type, show a vivid two-photon cell imaging and a remarkable photothermal conversion efficiency owing to their superior longitudinal surface plasmon resonance. Both in vitro cytotoxicity and in vivo immunotoxicity assays give substantial evidence of excellent biocompatibility attained in the NAs. The development of multifunctional targeting nanoprobes in this study could provide guidance for tailored design and controllable synthesis of heterostructured nanocomposites utilized for multimodal imaging and photothermal therapy of cancer.

Structure and dysprosium dopant engineering of gadolinium oxide nanoparticles for enhanced dual-modal magnetic resonance and fluorescence imaging.

We report a class of multi-functional core-shell nanoarchitectures, consisting of silica nanospheres as the core and Gd2O3:Dy3+ nanocrystals as the ultra-thin shell, that enable unique multi-color living cell imaging and remarkable in vivo magnetic resonance imaging. These types of targeted cell imaging nanoarchitectures can be used as a variety of fluorescence nanoprobes due to the multi-color emissions of the Gd2O3:Dy3+ nanophosphor. We also proposed a strategy of modulating core-shell structure design to achieve an enhanced magnetic resonance contrast ability of Gd2O3 nanoagents, and the classical Solomon-Bloembergen-Morgan theory was applied to explicate the mechanism underlying the enhancement. The as-synthesized ligand-free nanomaterial possesses a suitable particle size for cellular uptake as well as avoiding penetrating the blood-brain barrier with good water-solubility, stability, dispersibility and uniformity. The extremely low cytotoxicity and favorable biocompatibility obtained from in vitro and in vivo bioassays of the as-designed nanoparticles indicate their excellent potential as a candidate for functioning as a targeted nanoprobe.