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 (I550/I660) 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 in vitro 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.

Great efforts have been devoted to effective delivery of therapeutics into cells for cancer therapy. The exploration of nanoparticle based drug delivery systems (DDSs) faces daunting challenges due to the low efficacy of intracellular delivery. Herein, a localized drug delivery device consisting of photoluminescent mesoporous silica nanoparticles (PLMSNs) and a photothermal fibrous matrix was investigated. Specifically, PLMSNs modified with a pH-sensitive polydopamine (PDA) ‘gatekeeper’ served as a doxorubicin (DOX) carrier and could release DOX once the PLMSNs were taken up by the cancer cells. The PLMSNs were electrostatically assembled on the surface of an electrospun biodegradable poly(ε-caprolactone)/gelatin fibrous mesh incorporated with photothermal carbon nanoparticles (CNPs), leading to an implantable patch used as a localized delivery platform. Compared to free particulate DDSs, this implantable composite patch device was found to significantly enable a superior cell uptake effect and consequently enhance in vitro therapeutic efficacy against tumor cells. Namely, under near infrared irradiation, the photothermal effect of CNPs in the implantable patch weakens the electrostatic interaction between the PLMSNs and the poly(ε-caprolactone)/gelatin/CNP fibrous mesh, resulting in the controlled release of the PLMSNs and subsequent internalization into the tumor cells for more effective cancer cell killing. This implantable therapeutic device may therefore inspire other means of developing localized cancer therapy.

MicroRNAs (miRNAs) play a key role in regulating gene expression but can be associated with abnormalities linked to carcinogenesis and tumor progression. Hence there is increasing interest in developing methods to detect these non-coding RNA molecules in the human circulation system. Here, a novel FRET miRNA-195 targeting biosensor, based on silica nanofibers incorporated with rare earth-doped calcium fluoride particles (CaF2:Yb,Ho@SiO2) and gold nanoparticles (AuNPs), is reported. The formation of a sandwich structure, as a result of co-hybridization of the target miRNA which is captured by oligonucleotides conjugated at the surface of CaF2:Yb,Ho@SiO2 fibers and AuNPs, brings the nanofibers and AuNPs in close proximity and triggers the FRET effect. The intensity ratio of green to red emission, I541/I650, was found to decrease linearly upon increasing the concentration of the target miRNA and this can be utilized as a standard curve for quantitative determination of miRNA concentration. This assay offers a simple and convenient method for miRNA quantification, with the potential for rapid and early clinical diagnosis of diseases such as breast cancer.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been explored widely for application in cancer treatment. In this work, we describe the synthesis of CaTiO3:Yb,Er (CTO) nanofibers co-conjugated with Rose Bengal (RB) and gold nanorods (AuNRs), which offer the potential for combined upconversion photoluminescence (UCPL) and enhanced, synergistic PDT and PTT. Based on this delivery platform, RB and AuNRs served as the PDT and PTT agents, respectively. RB and AuNRs have strong and well-matched absorption with the green and red emissions of UCPL CTO nanofibers respectively, hence a single 980 nm continuous wave laser with deep tissue penetration can be employed to allow PDT and PTT to occur simultaneously. The nanocomposite can effectively convert the near-infrared (NIR) radiation from the laser into a combination of targeted hyperthermia and generation of reactive oxygen species (ROS). In comparison with PDT or PTT alone, the combined PDT/PTT treatment showed significantly enhanced suppression of the viability of Hep G2 cells in vitro, demonstrating its potential for use in oncology.

•Upconversion luminescent CaF2:Yb,Er nanoparticles were embedded within SiO2 nanofibers.•With PAA surface modification, nanofibers presented pH-triggered and optic-monitoring DOX releasing properties•Under NIR irradiation, DOX releasing kinetics accelerated and the in-vitro anti-cancer efficacy was enhanced.Smart localized drug delivery systems (LDDSs), with stimuli-responsive properties, offer tremendous opportunity for personalized cancer chemotherapy. In our work, an implantable ‘tumor patch’, consisting of upconversion (UC) photoluminescent CaF2:Yb,Er nanoparticles embedded within silica nanofibers (CaF2:Yb,Er@SiO2), was designed and synthesized for doxorubicin (DOX) delivery. DOX loading capacity of the fiber mesh was remarkably enhanced with assist of polyacrylic acid (PAA) functionalization. PAA modified CaF2:Yb,Er@SiO2 nanofibers presented highly corresponding optical response to DOX release kinetics. Accelerated drug release in acidic condition induced more rapid increase in the spectral intensity ratio of green to red emission (I550/I660), and vice versa. More importantly, under the irradiation of NIR (808 nm) laser, DOX release kinetics and consequently the in-vitro anti-cancer efficacy were enhanced. This study has thus offered another new implantable LDDS with NIR-triggered and monitored DOX delivery for personalized protocols in tumor chemotherapy.Download high-res image (111KB)Download full-size image

The investigation of nano-carriers with controllable and trackable drug release kinetics has attracted worldwide attention for new tumor theranostic strategies with catabatic side effects. Herein, a range of monodispersed core–shell structured photoluminescent SrTiO3:Yb3+,Er3+@mSiO2 nanoparticles were designed and synthesized. The surfactant cetyltrimethylammonium bromide (CTAB) was used to vary the microstructure of the mesoporous SiO2 shell. The specific surface area and pore volume increase proportionally with the content of CTAB. Consequently, the doxorubicin (DOX) loading capacity increases, and the drug release kinetics possesses a sustained behaviour. More importantly, the DOX release kinetics was found to correspond well to the evolution of the up-conversion luminescence (UCL) phenomenon. More rapid drug release induces more rapid photoluminescence enhancement, and vice versa. This study has therefore been anticipated to suggest another promising multifunctional drug delivery platform for advanced chemotherapies.

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 (I550/I660) 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 I550/I660 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.Keywords: doxorubicin; electrospinning; fluorescence resonance energy transfer (FRET); localized drug delivery system; SrTiO3:Er 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.

750–850 nm (NIR I) and 1000–1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.

Ferroelectric oxides with excellent electrical, mechanical and optical multifunctions play a vital role in future microdevices with diverse applications in energy, sensors and actuators. A series of Er doped PbZr0.52Ti0.48O3 (PZT:Er3+) nanofibers with tunable upconversion photoluminescence (PL) properties were successfully synthesized via a sol–gel based electrospinning process. By controlled crystallization, PZT:Er3+ nanofibers evolve from a polycrystalline to a single-crystalline-like structure, resulting in a remarkable increase in the visible upconversion emission intensity. It was uncovered that Er3+ doping site in PZT shifts from B site to A site with increase in crystallinity and crystal size. In addition, remarkable enhancement in red emission is observed with increased Er3+ doping concentration, which facilitates the modulation of emission colour from green to orange. Combined with the excellent ferroelectric properties of PZT, such spectral tunable PZT:Er3+ nanofibers are considered as a promising multifunctional candidate for integrated electro-mechano-optical devices.

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.Keywords: drug delivery; electrospinning; optical monitoring; pH-triggered; SrTiO3:Er nanofibers

•Porous hollow CaTiO3 nanofibers were synthesized via electrospinning.•The electrospinning process expedites phase separation leading to the formation of core–shell nanofibers.•Tuning of the hollow core and fiber dimension were achieved by altering the PVP/CTO molar ratio.The synthesis of porous CaTiO3 (CTO) nanotubes with controlled microstructure was demonstrated via a single-nozzle electrospinning approach. Homogenous sols comprising polyvinylpyrolidine (PVP), Pluronic F127 and CTO (metal salt) were electrospun, which resulted in fine CTO nanotubes due to phase separation phenomenon. PVP/CTO molar ratio was confirmed to induce the effective manipulation of its structural characteristics. Altering the ratio from 0.24 m to 0.12 m was found to result in the increased fiber diameter, from ~105 nm to ~230 nm, and the enhanced hollow structure (diameter of ~70 nm). Further development of biocompatible inorganic CaTiO3 nanotubes with such tunable hollow structures provides a platform for sustained drug loading and delivery.

•Fine bioactive glass (BG) nanofibers with controlled protein release kinetics.•The increased water content enhances the SiOSi network integrity of sol–gel BG fibers.•The ‘anchoring’ effect of the apatite layers formed prohibits protein releasing.•More crystalline apatite layer induces sustained release kinetic of protein molecules.A range of fine bioactive glass (BG) fibers with different hydrolysis degree were synthesized via a sol–gel and electrospinning approach. Due to the increased water/TEOS ratio (X ratio) from 2 to 8, the SiOSi network integrity of BG fibers was dramatically enhanced. With a designed protein loading method using simulated body fluid (SBF)/bovine serum albumin (BSA) mixture solution, the tunable protein releasing was successfully achieved. The varied hydrolysis degree of BG fibers was found to induce distinctive releasing behavior. The protein release kinetics intends to present a more controlled and sustained manner with the decreased X ratio from 8 to 2, and such phenomenon is mainly attributed to the ‘anchoring’ effect of the crystalline apatite mineral layers formed at the fiber surface. This study has therefore offered another way of thinking in the investigation of feasible multifunctionalization strategies for bioactive glasses, and thus provided an impetus to the current research for future advanced BG scaffold materials.

Nanocrystalline silicon (nc-Si) films were synthesized via different re-crystallization approaches from amorphous silicon (α-Si:H) films deposited using plasma enhanced chemical vapor deposition (PECVD). The microstructure evolution with various annealing conditions was investigated via high resolution transmission electron microscopy (HRTEM) and Raman spectrometry. It was found that, compared with the conventional solid phase crystallization (SPC) annealing, a rapid thermal process (RTP) pre-annealing at 600 °C for 60 s can significantly enhance the recrystallization process and the electrical conductivity of nc-Si films. In addition, for the nc-Si films with similar crystal sizes, it was uncovered that the logarithm of conductivity presented a linear relationship with the crystalline volume fraction. This study has therefore been an important step forward to the future synthesis of the nc-Si films with manipulated microstructure and electrical conductivity for further applications.Highlights► The nc-Si films with controlled microstructure and electrical conductivity (σ) ► The crystal size was controlled at ~ 5 nm at the controlled process condition. ► Logarithm of σ is linearly proportional to the crystallized fraction under the circumstance above. ► RTP enhanced the recrystallization and conductivity of the Si films.

A range of silica nanofibers with refined mesoporous microstructures were successfully synthesized via the combination of electrospinning and the sol–gel method. It was found that the concentration of nonionic surfactant Pluronic F127 (EO106PO70EO106) significantly influenced the morphology and mesoporous structure of silica nanofiber. With the reduced F127/Tetraethyl orthosilicate (TEOS) mass ratio, from 0.28 to 0.14, the diameter of silica nanofibers decreased from 453 nm to 130 nm, and more importantly, the size and the orientation of the internal mesopores were remarkably regulated. It has therefore been a critical step forward to a new hierarchical silica fiber for modern optical and biomedical applications.Highlights► A range of silica nanofibers with adjustable diameters were successfully synthesized via the sol–gel method and electrospinning. ► The silica nanofibers with orientated mesoporous structure have been achieved via the reduction of F127/TEOS mass ratio from 0.28 to 0.14. ► During the “disordered to ordered” process, the dominant pore-forming mechanism was found to be phase separation under rapid solvent evaporation.

•Ag-silica composite nanotubes with controlled wall structures, from dense to ‘lace-like’.•Ag doping weakens silica network integrity dramatically.•‘Lace-like’ nanotube wall structure is induced by the Ag particles reduced from AgOSi bondings in the nanotubes.•The ‘lace-like’ wall structure induces the enhanced antibacterial property.A range of Ag-silica composite nanotubes with tailored wall structures were successfully synthesized in situ by single-nozzle electrospinning. By increasing AgNO3 concentration, the wall structure of Ag-silica tubes changes from dense to porous, and eventually turns into a ‘lace-like’ structure. This is attributed to Ag ions doping into the SiOSi network of precursors, as illustrated in FTIR study. More importantly, Ag-silica composite nanotubes show robust antibacterial activity against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli microorganisms. Therefore, it is a breakthrough of the nanostructure biomaterial research for future medical applications that require strong antibacterial properties.

•The sandwich structural low-e glass was prepared on an industrial line.•The film showed stable morphology and functional property under low temperature.•The functional property decreased dramatically after long time tempering at 650 °C.The low-emission glass was prepared via depositing fluorine-doped tin oxide thin film on glass substrate by atmospheric pressure chemical vapor deposition method. The as-deposited low-emission glass was found to present a SnO2:F/SiCxOy/glass sandwich structure via focused ion beam technique and transmission microscopic measurement. After tempering process at ~ 650 °C with varied periods, the electrical and optical properties of the SnO2:F thin film remained stable for less than 10 min, but decreased dramatically when the tempering period exceeded 10 min, which was mainly due to the oxygen chemisorptions and fluorine ion diffusion. It was observed that the SnO2:F thin films presented uniform polycrystalline nature of cassiterite structure throughout the tempering process. The study has therefore suggested the appropriate tempering conditions for the SnO2:F low-emission glass, and provided a critical guidance for further energy-saving glass applications.

A series of amorphous carbon-based films were deposited on the nanostructured Ag layers to observe surface plasmon (SP) enhanced photoluminescence (PL). The dependence of PL peak wavelength and intensity on the film composition and the nanostructure of the Ag layers were systematically investigated. The PL wavelength was tuned from 442 nm to 635 nm by varying the carbon content of the as-deposited carbon-based films. The nanostructure of Ag layers varied from nanoparticles (NPs) to continuous films via process control. With the SPs generated at the carbon-based film/Ag layer interface, the PL intensity was found to be significantly enhanced with a peak enhancement factor of 6, and the light emission range of the composite films was extended to 434–653 nm. The dependence of PL intensity on the spectral overlap between the carbon-based films and plasmon resonant Ag layers, Ag surface morphology and the internal quantum efficiency (IQE) of the carbon-based films was discussed. The redshift of SP resonance with the increasing refractive index of the upper carbon-based films was observed.Highlights► The light emission of amorphous carbon-based films is enhanced by surface plasmons. ► The light emission range is extended by surface plasmons. ► SP resonance redshifts with increasing refractive indices of the luminescent films. ► SPs are promising to enhance the full-color light emission of carbon-based films.

A range of mesoporous silica nanoparticles (MSNs) with controlled microstructural characteristics were successfully prepared via the binary surfactant templated synthesis approach with varied concentration of triblock copolymer Pluronic F127. The relationship between the MSNs structural evolution and the surfactant concentration was extensively discussed. Ibuprofen (IBU) was loaded as drug model to uncover the in vitro drug releasing kinetics. It was found that the quantity of the drug loaded mainly depended on the specific surface area, while the drug releasing rate was dominantly determined by the length and curvature of the mesopores. This study has uncovered the core influential factors of MSNs system on its drug releasing properties, and thus demonstrated a facile approach to prepare MSNs with manipulated structural characteristics for drug delivery applications.Graphical abstractHighlights► The as-prepared MSNs with manipulated morphology and structural characteristics by varying F127 concentration. ► The pore length and curvature was changed with the shape of MSNs. ► The drug-loading amount was determined by specific surface areas. ► The length and curvature of the mesopores impact on the drug releasing characteristics.

Ferroelectric oxides with excellent electrical, mechanical and optical multifunctions play a vital role in future microdevices with diverse applications in energy, sensors and actuators. A series of Er doped PbZr0.52Ti0.48O3 (PZT:Er3+) nanofibers with tunable upconversion photoluminescence (PL) properties were successfully synthesized via a sol–gel based electrospinning process. By controlled crystallization, PZT:Er3+ nanofibers evolve from a polycrystalline to a single-crystalline-like structure, resulting in a remarkable increase in the visible upconversion emission intensity. It was uncovered that Er3+ doping site in PZT shifts from B site to A site with increase in crystallinity and crystal size. In addition, remarkable enhancement in red emission is observed with increased Er3+ doping concentration, which facilitates the modulation of emission colour from green to orange. Combined with the excellent ferroelectric properties of PZT, such spectral tunable PZT:Er3+ nanofibers are considered as a promising multifunctional candidate for integrated electro-mechano-optical devices.

750–850 nm (NIR I) and 1000–1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been explored widely for application in cancer treatment. In this work, we describe the synthesis of CaTiO3:Yb,Er (CTO) nanofibers co-conjugated with Rose Bengal (RB) and gold nanorods (AuNRs), which offer the potential for combined upconversion photoluminescence (UCPL) and enhanced, synergistic PDT and PTT. Based on this delivery platform, RB and AuNRs served as the PDT and PTT agents, respectively. RB and AuNRs have strong and well-matched absorption with the green and red emissions of UCPL CTO nanofibers respectively, hence a single 980 nm continuous wave laser with deep tissue penetration can be employed to allow PDT and PTT to occur simultaneously. The nanocomposite can effectively convert the near-infrared (NIR) radiation from the laser into a combination of targeted hyperthermia and generation of reactive oxygen species (ROS). In comparison with PDT or PTT alone, the combined PDT/PTT treatment showed significantly enhanced suppression of the viability of Hep G2 cells in vitro, demonstrating its potential for use in oncology.