A Dual-Color Luminescent Localized Drug Delivery System with Ratiometric-Monitored Doxorubicin Release Functionalities

Implantable localized drug delivery systems (LDDSs) have been intensively investigated for cancer therapy. However, the anticancer agent release behavior as well as the local therapeutic process in the complex physiological environment remains a dark zone and consequently hinders their clinical applications. Herein, a series of Er³⁺-doped electrospun strontium titanate (SrTiO₃, STO) nanofibers with refined microstructural characteristics were exploited as a localized carrier for doxorubicin (DOX) delivery due to its light-responsive functionalities as well as expected biocompatibility. The highest DOX loading capacity and sustained releasing kinetics were obtained from the nanofibers with the highest surface area and lowest pore dimensions. Consequently, such nanofibers presented stronger in vitro anticancer efficacy to Hep G2 cells compared to that of other samples. More importantly, the amount of drug released was monitored by the ratio of green-to-red emission (<i>I</i>₅₅₀/<i>I</i>₆₆₀) due to the fluorescence resonance energy transfer (FRET) effect built between DOX molecules and upconversion photoluminescent nanofibers. The selective quenching effect of green emission due to DOX molecules was gradually weakened with drug releasing progress, whereas the intensity of red emission barely changed, resulting in an increased <i>I</i>₅₅₀/<i>I</i>₆₆₀ ratio. Such color evolution can be feasibly visualized by the naked eye. Monitoring with a spectral intensity ratio eliminates the disturbance of uncertainties in the complex physiological environment compared to just referring to the emission intensity. Such dual-color luminescent STO:Er nanofibers, designed based on the FRET mechanism, are therefore considered to be a promising new LDDS platform with ratiometric-monitored DOX release functionalities for future localized tumor therapeutic strategies

Tuning Interfacial Magnetic Ordering via Polarization Control in Ferroelectric SrTiO₃/PbTiO₃ Heterostructure

The electromagnetic properties at the interface of heterostructure are sensitive to the interfacial crystal structure and external field. For example, the two-dimensional magnetic states at the interface of LaAlO₃/SrTiO₃ are discovered and can further be controlled by electric field. Here, we study two types of heterostructures, TiO₂/PbTiO₃ and SrTiO₃/PbTiO₃, using first-principle electronic structure calculations. We find that the ferroelectric polarization discontinuity at the interface leads to partially occupied Ti 3d states and the magnetic moments. The magnitude of the magnetic moments and the ground-state magnetic coupling are sensitive to the polarization intensity of PbTiO₃. As the ferroelectric polarization of PbTiO₃ increases, the two heterostructures show different magnetic ordering that strongly depends on the electron occupation of the Ti t_2g orbitals. For the TiO₂/PbTiO₃ interface, the magnetic moments are mostly contributed by degenerated d<i>_yz</i>/d<i>_xz</i> orbitals of interfacial Ti atoms and the neighboring interfacial Ti atoms form ferromagnetic coupling. For SrTiO₃/PbTiO₃ interface, the interfacial magnetic moments are mainly contributed by occupied d_<i>xy</i> orbital because of the increased polarization intensity, and as the electron occupation increases, there exists a transition of the magnetic coupling between neighboring Ti atoms from ferromagnetism to antiferromagnetism via the superexchange interaction. Our study suggests that manipulating the polarization intensity is one effective way to control interfacial magnetic ordering in the perovskite oxide heterostructures

Polarization-Modified Upconversion Luminescence in Er-Doped Single-Crystal Perovskite PbTiO₃ Nanofibers

Understanding the energy transition which is influenced by doping ions and host materials in the upconversion (UC) physical processes is of vital importance for further optimizing performance and extending applications of UC materials. In this work, we have selected 4% Er-doped perovskite PbTiO₃ (PTO) nanofibers as a model system to explore the effects of tetragonality and polarization on UC photoluminescence (PL) properties. By means of in situ X-ray diffraction, the tetragonality and polarization of these nanofibers have been determined to gradually decrease with an increasing of the temperature from 50 to 300 K, leading to obvious enhancements in UC green band emission of 523 nm (about 43 times) and red band emission of 656 nm (about 8 times), in contrast to the decreased green and red UC intensities in Er-doped BaTiO₃ or PTO particles. Moreover, the significant enhancement in the intensity ratio of green to red bands from 0.17 to 0.86 has been achieved, indicating that the emission enhancement is highly wavelength-dependent. On the basis of in situ UC decay curves from 50 to 300 K, the UC lifetimes of the ⁴S_3/2 and ⁴F_9/2 level have been derived to be 128.04 ± 0.47 μs and 278.10 ± 1.07 μs at 50 K, respectively, and the values are basically maintained as the temperature increases. The observed UC phenomena in Er-doped perovskite PTO nanofibers can be ascribed to an assisted effect of the low-energy E­(1TO) phonon on the UC process. Such phonon energy can be easily tailored by the tetragonality and polarization; thus, a modification of UC emissions in Er-doped PTO nanofibers has been achieved. The findings in this work could provide new insights into understanding the UC process in perovskite oxides and offer an opportunity to tune UC emission by an external field, such as an electric field, in addition to temperature

pH-Triggered SrTiO₃:Er Nanofibers with Optically Monitored and Controlled Drug Delivery Functionality

The design of multifunctional localized drug delivery systems (LDDSs) has been endeavored in the past decades worldwide. The matrix material of LDDSs is known as a crucial factor for the success of its transformation from the laboratory to clinical practices. Herein, a biocompatible ceramic, strontium titanate (SrTiO₃, STO), was utilized as the matrix. A variety of fine Er doped SrTiO₃ (STO:Er) nanofibers were fabricated via electrospinning. After the surface functionalization with amino groups, the drug loading capacity of STO:Er nanofibers is dramatically increased. The nanofibers present a rather sustained drug releasing behavior in the media with pH of 7.4, and the release kinetics is significantly accelerated with the decreased pH value from 7.4 to 4.7. Furthermore, the intensity of the spectrum emitted from the STO:Er nanofibers corresponds well with the drug releasing progress under the excitation of near-infrared spectrum (∼980 nm). Fast drug release behavior (in an acid environment) induces a rapid intensity enhancing effect of photoluminescence emission and vice versa. The main mechanism is attributed to the quenching effect induced by the C-Hx groups of IBU molecules with vibration frequencies from 2850 to 3000 cm^–1. Such new STO:Er nanofibers with pH-triggered and optically monitored drug delivery functionalities have therefore been considered as another new localized drug delivery platform for modern tumor diagnosis and therapy

A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release

Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb³⁺/Er³⁺ codoped CaTiO₃ (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (<i>I</i>₅₅₀/<i>I</i>₆₆₀) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced <i>in vitro</i> anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy

Optically Monitoring Mineralization and Demineralization on Photoluminescent Bioactive Nanofibers

Bone regeneration and scaffold degradation do not usually follow the same rate, representing a daunting challenge in bone repair. Toward this end, we propose to use an external field such as light (in particular, a tissue-penetrating near-infrared light) to precisely monitor the degradation of the mineralized scaffold (demineralization) and the formation of apatite mineral (mineralization). Herein, CaTiO₃:Yb³⁺,Er³⁺@bioactive glass (CaTiO₃:Yb³⁺,Er³⁺@BG) nanofibers with upconversion (UC) photoluminescence (PL) were synthesized. Such nanofibers are biocompatible and can emit green and red light under 980 nm excitation. The UC PL intensity is quenched during the bone-like apatite formation on the surface of the nanofibers in simulated body fluid; more mineral formation on the nanofibers induces more rapid optical quenching of the UC PL. Furthermore, the quenched UC PL can recover back to its original magnitude when the apatite on the nanofibers is degraded. Our work suggests that it is possible to optically monitor the apatite mineralization and demineralization on the surface of nanofibers used in bone repair

Interfacial Multiferroics of TiO₂/PbTiO₃ Heterostructure Driven by Ferroelectric Polarization Discontinuity

Novel phenomena appear when two different oxide materials are combined together to form an interface. For example, at the interface of LaAlO₃/SrTiO₃, two-dimensional conductive states form to avoid the polar discontinuity, and magnetic properties are found at such an interface. In this work, we propose a new type of interface between two nonmagnetic and nonpolar oxides that could host a magnetic state, where it is the ferroelectric polarization discontinuity instead of the polar discontinuity that leads to the charge transfer, forming the interfacial magnetic state. As a concrete example, we investigate by first-principles calculations the heterostructures made of ferroelectric perovskite oxide PbTiO₃ and nonferroelectric polarized oxide TiO₂. We show that charge is transferred to the interfacial layer forming an interfacial ferromagnetic ordering that may persist up to room temperature. Especially, the strong coupling between bulk ferroelectric polarization and interface ferromagnetism represents a new type of magnetoelectric effect, which provides an ideal platform for exploring the intriguing interfacial multiferroics. The findings here are important not only for fundamental science but also for promising applications in nanoscale electronics and spintronics

Growth and Bending-Sensitive Photoluminescence of a Flexible PbTiO₃/ZnO Nanocomposite

A brushlike PbTiO₃ (PTO)/ZnO nanocomposite with ZnO nanowires (NWs) grown epitaxially on the surface of single-crystal ferroelectric tetragonal PTO NWs is successfully fabricated onto a flexible substrate via a two-step hydrothermal process. In this nanocomposite, a ZnO NW grew along [0001] on the (101) plane of the core PTO NW with a lattice mismatch of 1.06% to form an effective ferroelectric/semiconductor interface. It is found that the ultraviolet photoluminescence emission of the nanocomposite could be easily tuned by its bending curvatures at room temperature. This intriguing phenomenon can be understood by the bending-induced polarization field from the PTO NW, which could reduce the bending degree of the energy band of the ZnO NWs through the interface. Throughthe design of an effective interface, this kind of ferroelectric/semiconductor nanocomposite may find potential applications in sensor and piezophotonic nanodevices

Asymmetric Modulation on Exchange Field in a Graphene/BiFeO₃ Heterostructure by External Magnetic Field

Graphene, having all atoms on its surface, is favorable to extend the functions by introducing the spin–orbit coupling and magnetism through proximity effect. Here, we report the tunable interfacial exchange field produced by proximity coupling in graphene/BiFeO₃ heterostructures. The exchange field has a notable dependence with external magnetic field, and it is much larger under negative magnetic field than that under positive magnetic field. For negative external magnetic field, interfacial exchange coupling gives rise to evident spin splitting for <i>N</i> ≠ 0 Landau levels and a quantum Hall metal state for <i>N</i> = 0 Landau level. Our findings suggest graphene/BiFeO₃ heterostructures are promising for spintronics