Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

A Proof-of-Concept Study on the Theranostic Potential of 177 Lu-labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177 Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177 Lu-DOTA-PEG-CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177 Lu-DOTA-PEG-CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177 Lu-DOTA-PEG-CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177 Lu-DOTA-PEG-CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177 Lu-DOTA-PEG-CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177 Lu radiolabeled compounds efficiently.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([211At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice. In biodistribution analysis, [211At]SAB-Oct achieved the highest concentration in the SCLC tumors up to 3 h after injection as time proceeded. A single intravenous injection of [211At]SAB-Oct (370 kBq) was sufficient to suppress SSTR2-positive SCLC tumor growth in treated mice by inducing DNA double-strand breaks. Additionally, a multitreatment course (370 kBq followed by twice doses of 370 kBq for a total of 1110 kBq) inhibited the growth of the tumor compared to the untreated control group without significant off-target toxicity. Surprisingly, we found that [211At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [211At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.

Multimodal Imaging-Guided Strategy for Developing 177Lu-Labeled Metal-Organic Framework Nanomedicine with Potential in Cancer Therapy.

Nano-metal-organic frameworks (nano-MOFs) labeled with radionuclides have shown great potential in the anticancer field. In this work, we proposed to combine fluorescence imaging (FI) with nuclear imaging to systematically evaluate the tumor inhibition of new nanomedicines from living cancer cells to the whole body, guiding the design and application of a high-performance anticancer radiopharmaceutical to glioma. An Fe-based nano-MOF vector, MIL-101(Fe)/PEG-FA, was decorated with fluorescent sulfo-cyanine7 (Cy7) to investigate the binding affinity of the targeting nanocarriers toward glioma cells in vitro, as well as possible administration modes for in vivo cancer therapy. Then, lutetium-177 (177Lu)-labeled MIL-101(Fe)/PEG-FA was prepared for high-sensitive imaging and targeted radiotherapy of glioma in vivo. It has been demonstrated that the obtained 177Lu-labeled MIL-101(Fe)/PEG-FA can work as a complementary probe to rectify the cancer binding affinity of the prepared nanocarrier given by fluorescence imaging, providing more precise biodistribution information. Besides, 177Lu-labeled MIL-101(Fe)/PEG-FA has excellent antitumor effect, leading to cell proliferation inhibition, upregulation of intracellular reactive oxygen species, tumor growth suppression, and immune response-related protein and cytokine upregulation. This work reveals that optical imaging and nuclear imaging can work complementarily as multimodal imaging in the design and evaluation of anticancer nanomedicine, offering a MIL-101(Fe)/PEG-FA-based pharmaceutical with potential in tumor endoradiotherapy.

Sequencing, Functional Annotation, and Interaction Prediction of mRNAs and Candidate Long Noncoding RNAs Originating from Tea Leaves During Infection by the Fungal Pathogen Causing Tea Leaf Spot, Didymella bellidis.

Tea leaf spot caused by Didymella bellidis can seriously reduce the productivity and quality of tea (Camellia sinensis var. sinensis) leaves in Guizhou Province, southwest China. Analysis of the relationship between messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) of tea could provide insights into the plant-pathogen interaction. In this study, high-throughput sequencing of mRNAs and lncRNAs from tea leaves during infection by D. bellidis was conducted using the Illumina Novaseq 6000 platform. Infection by D. bellidis hyphae resulted in up- or downregulation of 553 and 191 of the differentially expressed mRNAs (DEmRNAs), respectively. As the S gene number (total number of genes with significantly differential expression annotated in the specified Gene Ontology [GO] database), three were enriched with respect to the defense response to the fungus at the biological process level. Expression of the DEmRNAs peroxidase 21 (TEA000222.1) and mcht-2 (TEA013240.1) originating from tea leaves were upregulated during challenge by D. bellidis hyphae, whereas expression of the LRR receptor-like serine/threonine-protein kinase ERECTA (TEA016781.1) gene was downregulated. The infection of D. bellidis hyphae resulted in up- or downregulation of 227 and 958 of the differentially expressed lncRNAs (DElncRNAs). The DEmRNAs associated with uncharacterized LOC101499401 (TEA015626.1), uncharacterized protein (TEA014125.1), structural maintenance of chromosomes protein 1 (TEA001660.1), and uncharacterized protein (TEA017727.1) occurred as a result of cis regulation by DElncRNAs MSTRG.20036, MSTRG.3843, MSTRG.26132, and MSTRG.56701, respectively. The expression profiling and lncRNA/mRNA association prediction in the tea leaves infected by D. bellidis will provide a valuable resource for further research into disease resistance.

Sorption behavior and mechanism of U(VI) on Tamusu clay in the presence of U(VI)-CO3 complexes.

The sorption behavior of U(VI) on Tamusu clay sampled from a pre-selected high-level radioactive waste (HLW) disposal site in Inner Mongolia (China) was studied systematically in the U(VI)-CO3 solution at pH 7.8 by batch experiments. The results demonstrated that the distribution coefficients (Kd) decreased with the increasing values of pHinitial, [U(VI)]initial, and ionic strength, but increased with the extended time and the rising temperature. The sorption was a pH-dependent, heterogeneous, spontaneous, and endothermic chemical process, which could be better described by Freundlich isothermal model and pseudo-second-order kinetic model. The presence of humic acid (HA) or fulvic acid (FA) significantly inhibited the U(VI) sorption, due to the enhanced electrostatic repulsion between the negatively charged HA/FA adsorbed on the clay surface and the negative U(VI) species, as well as the well dispersed HA/FA aggregates in solution wrapping the U(VI) species. The FTIR and XPS spectra indicated that the HCO3- groups on the surface of Tamusu clay after hydroxylation and the ‒OH groups in HA/FA were involved in the U(VI) sorption. The results reported here provide valuable insights into the further understanding of U(VI) migration in geological media.

Porphyrin-based hydrogen-bonded organic framework for visible light driven photocatalytic removal of U(VI) from real low-level radioactive wastewater.

The reduction of soluble U(VI) to insoluble U(IV) precipitates by visible light is an environmentally friendly and highly effective strategy to remove uranium from uranium-containing radioactive wastewater. Herein, a porous hydrogen-bonded organic framework (HOF) of UPC-H4a was self-assembled by intermolecular hydrogen bonds of 5,10,15,20-tetra(4-(2,4-diaminotriazine)phenyl) porphyrin to remove U(VI) from aqueous solution. UPC-H4a has high crystallinity with permanent porosity, excellent photocatalytic property, good chemical stability, and strong photocatalytic reducibility. The experiments showed that UPC-H4a removed 98.18% of U(VI) after illumination for 120 min, with high selectivity, strong ion interference resistance, and good reusability. A real low-level radioactive wastewater was employed to estimate the potential of UPC-H4a for practical application and its removal rate can reach 66.14% in the presence of redox competing metal ions, exhibiting great potential for practical application. The DFT calculations and EPR spectra revealed that a more negative electrostatic potential of DAT-porphyrin and the formed intermolecular hydrogen bonds in UPC-H4a can facilitate the participation of photogenerated electrons in the O2/∙O2- reaction, and the radical of ∙O2- was proved to be the critical participant in U(VI) photoreduction. The discovery of UPC-H4a in this work will help to develop more potential applications of HOFs as photocatalysts in radioactive wastewater treatment.

A Smart Benzothiazole-Based Conjugated Polymer Nanoplatform with Multistimuli Response for Enhanced Synergistic Chemo-Photothermal Cancer Therapy.

The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.

Extracellular biomineralization of uranium and its toxicity alleviation to Bacillus thuringiensis X-27.

Uranium biomineralization can slow uranium migration in the environment and thus prevent it from further contaminating the surroundings. Investigations into the uranium species, pH, inorganic phosphate (Pi) concentration, and microbial viability during biomineralization by microorganisms are crucial for understanding the mineralization mechanism. In this study, Bacillus thuringiensis X-27 was isolated from soil contaminated with uranium and was used to investigate the formation process of uranium biominerals induced by X-27. The results showed that as biomineralization proceeded, amorphous uranium-containing deposits were generated and transformed into crystalline minerals outside cells, increasing the overall concentration of uramphite. This is a cumulative rather than abrupt process. Notably, B. thuringiensis X-27 precipitated uranium outside the cell surface within 0.5 h, while the release of Pi into the extracellular environment and the change of pH to alkalescence further promoted the formation of uramphite. In addition, cell viability determination showed that the U(VI) biomineralization induced by B. thuringiensis X-27 was instrumental in alleviating the toxicity of U(VI) to cells. This work offers insight into the mechanism of U(VI) phosphate biomineralization and is a reference for bioremediation-related studies.

Unusual uranium biomineralization induced by green algae: Behavior investigation and mechanism probe.

As a biosorbent, algae are frequently used for the biotreatment or bioremediation of water contaminated by heavy metal or radionuclides. However, it is unclear that whether or not the biomineralization of these metal or radionuclides can be induced by algae in the process of bioremediation and what the mechanism is. In this work, Ankistrodsemus sp. has been used to treat the uranium-contaminated water, and more than 98% of uranium in the solution can be removed by the alga, when the initial uranium concentration ranges from 10 to 80 mg/L. Especially, an unusual phenomenon of algae-induced uranium biomineralization has been found in the process of uranium bioremediation and its mineralization mechanism has been explored by multiple approaches. It is worth noticing that the biomineralization of uranium induced by Ankistrodsemus sp. is significantly affected by contact time and pH. Uranium is captured rapidly on the cell surface via complexation with the carboxylate radical, amino and amide groups of the microalgae cells, which provides nucleation sites for the precipitation of insoluble minerals. Uranium stimulates Ankistrodsemus sp. to metabolize potassium ions (K+), which may endow algae with the ability to biomineralize uranium into the rose-like compreignacite (K2[(UO2)6O4(OH)6]•8H2O). As the time increased, the amorphous gradually converted into compreignacite crystals and a large number of crystals would expand over both inside and outside the cells. To the best of our knowledge, this is the first investigated microalgae with a time-dependent uranium biomineralization ability and superior tolerance to uranium. This work validates that Ankistrodsemus sp. is a promising alga for the treatment of uranium-contaminated wastewater.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression.

BACKGROUND: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. METHODS: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. RESULTS: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. CONCLUSIONS: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TAT-CDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

Targeted Alpha Therapy of Glioma Using 211At-Labeled Heterodimeric Peptide Targeting Both VEGFR and Integrins.

Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.

Emerging Function of Ecotype-Specific Splicing in the Recruitment of Commensal Microbiome.

In recent years, host-microbiome interactions in both animals and plants has emerged as a novel research area for studying the relationship between host organisms and their commensal microbial communities. The fitness advantages of this mutualistic interaction can be found in both plant hosts and their associated microbiome, however, the driving forces mediating this beneficial interaction are poorly understood. Alternative splicing (AS), a pivotal post-transcriptional mechanism, has been demonstrated to play a crucial role in plant development and stress responses among diverse plant ecotypes. This natural variation of plants also has an impact on their commensal microbiome. In this article, we review the current progress of plant natural variation on their microbiome community, and discuss knowledge gaps between AS regulation of plants in response to their intimately related microbiota. Through the impact of this article, an avenue could be established to study the biological mechanism of naturally varied splicing isoforms on plant-associated microbiome assembly.

Multi-Omics Analysis Reveals that the Antimicrobial Kasugamycin Potential Targets Nitrate Reductase in Didymella segeticola to Achieve Control of Tea Leaf Spot.

Because of the lack of effective disease management measures, tea leaf spot-caused by the fungal phytopathogen Didymella segeticola (syn. Phoma segeticola)-is an important foliar disease. The important and widely used agricultural antimicrobial kasugamycin (Ksg), produced by the Gram-positive bacterium Streptomyces kasugaensis, effects high levels of control against crop diseases. The results of this study indicated that Ksg could inhibit the growth of D. segeticola hyphae in vitro with a half-maximal effective concentration (EC50) of 141.18 µg ml-1. Meanwhile, the curative effect in vivo on the pathogen in detached tea leaves also demonstrated that Ksg induced some morphological changes in organelles, septa, and cell walls as observed by optical microscopy and by scanning and transmission electron microscopy. This may indicate that Ksg disturbs biosynthesis of key metabolites, inhibiting hyphal growth. Integrated transcriptomic, proteomic, and bioinformatic analyses revealed that differentially expressed genes or differentially expressed proteins in D. segeticola hyphae in response to Ksg exposure were involved with metabolic processes and biosynthesis of secondary metabolites. Molecular docking studies indicated that Ksg may target nitrate reductase (NR), and microscale thermophoresis assay showed greater affinity with NR, potentially disturbing nitrogen assimilation and subsequent metabolism. The results indicated that Ksg inhibits the pathogen of tea leaf spot, D. segeticola, possibly by binding to NR, disturbing fungal metabolism, and inducing subsequent changes in hyphal growth and development.

The dynamic behavior and mechanism of uranium (VI) biomineralization in Enterobacter sp. X57.

The important role of microbes in the biomineralization and migration behavior of uranium in the field of environmental chemistry has been well emphasized in previous work. However, limited work on mineralization processes of indigenous microorganism has prevented us from a deeper understanding of the process and mechanisms of uranium biomineralization. In this work, the dynamic process and mechanism of uranium biomineralization in Enterobacter sp. X57, a novel uranium-tolerant microorganism separated from uranium contaminated soil, were systematically investigated. Enterobacter sp. X57 can induce intracellular mineralization of U (VI) to Uramphite (NH4UO2PO4·3H2O) under neutral conditions by alkaline phosphatase. In this biomineralization process, soluble U (VI) first bonded with the amino and phosphate groups on the plasma membrane, providing initial nucleation site for the formation of U (VI) biominerals. Then the impairment of cell barrier function and the enhancement of alkaline phosphatase metabolism occurred with the accumulation of uranium in cells, creating a possible pathway for soluble U (VI) to diffuse into the cell and be further mineralized into U (VI)-phosphate minerals. All the results revealed that the intracellular biomineralization of uranium by Enterobacter sp. X57 was a combined result of biosorption, intracellular accumulation and phosphatase metabolism. These findings may contribute to a better understanding of uranium biomineralization behavior and mechanism of microorganisms, as well as possible in-situ bioremediation strategies for uranium by indigenous microorganisms.

In Vitro Anticancer Ability of Nano Fluorescent 111 In-MIL-68/PEG-FA on Hela Cells.

In past decades, nanoscale metal-organic frameworks (NMOFs) have drawn more and more attention in multimodal imaging and targeting therapy of various malignant cancers. Here, we proposed to dope 111 In into fluorescent In-based NMOFs (In-MIL-68-NH2 ), with an attempt to prepare a new nanomedicine with great anticancer potential. As a proof of concept, the obtained NMOF (In-MIL-68/PEG-FA) with targeting motifs is able to act as a fluorescent probe to achieve Hela cell imaging. Moreover, the Auger electron emitter 111 In built in corresponding radioactive NMOF (111 In-MIL-68/PEG-FA) can bring clear damage to cancer cells, leading to a high cell killing rate of 59.3 % within 48 h. In addition, the cell cycle presented a significant dose-dependent G2/M inhibiting mode, which indicates that 111 In-MIL-68/PEG-FA has the ability to facilitate the cancer cells to enter apoptotic program. This work demonstrated the potential of 111 In-labelled NMOFs in specific killings of cancer cells, providing a new approach to develop nanomedicines with theranostic function.