Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

An electrochemical sensor based on AuPd@FexOy nanozymes for a sensitive and in situ quantitative detection of hydrogen peroxide in real samples.

The hydrogen peroxide (H2O2) levels in living organisms and environment have strong effects on many biological processes inducing cell apoptosis/cell necrosis and wound disinfection. Therefore, it is important to have an accurate and in situ detection of H2O2. Herein, an AuPd@FexOy nanozyme-based electrochemical (EC) sensor (termed as AuPd@FexOy NPs/GCE) with good stability and anti-interference ability has been prepared for the detection of H2O2 by differential pulse voltammetry (DPV) and chronoamperometry dual-measurement modes. The AuPd@FexOy NPs/GCE exhibits good linear relationships in the ranges from 13.0 to 6.0 × 103 µM (DPV measurement) and 50 to 1.0 × 103 µM (chronoamperometry measurement), low detection limits (LODs) of 1.6 µM (DPV measurement) and 3.0 µM (chronoamperometry measurement) and high sensitivities of 83.8 nA µM-1 cm-2 (DPV measurement) and 120.7 nA µM-1 cm-2 (chronoamperometry measurement). The practicability of the as-prepared AuPd@FexOy NPs/GCE has been demonstrated by an in situ real-time detection of H2O2 released from adherent living MCF-7 cells triggered by varying amounts of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) from 0.5 to 3.0 µM and the quantitative determination of H2O2 in commercial disinfectants.

Laser desorption/ionization on nanostructured silicon: morphology matters.

The surface morphology of the silicon nanostructure plays a crucial role in the laser desorption/ionization (LDI) process. Understanding the correlation between the surface morphology and LDI performance is the foundation for creating silicon substrates with high LDI efficiency. Most of the present studies focus only on the structural parameters (such as porosity, depth, total surface area, dimension, etc.) of a single structure, but their effects on LDI efficiency vary with the types of silicon structures. Herein, two representative types of silicon nanostructures, porous silicon (PSi) and thorny silicon (TSi), were created to address this issue. The results indicate that the PSi substrate can generate a stronger heat effect and is beneficial to desorption; the TSi substrate can facilitate electron transfer and is favorable to ionization. Subsequently, the assertion was further confirmed by simultaneously detecting a dozen of standard samples and a real sample on both the TSi and PSi substrates, in which PSi can significantly enhance the detection signals of organic salts, whereas the TSi substrate can greatly increase the LDI efficiencies of neutral analytes. This finding provides a foundation for improving the LDI performance by tailoring silicon nanostructures, which is helpful for designing and creating substrates with high LDI performance.

Generation of an induced pluripotent stem cell line from a patient with Angelman syndrome carrying UBE3A mutation.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression or function defects of the UBE3A gene in the maternal chromosome region 15q11-13. In order to study the pathogenesis of Angelman syndrome and further search for its effective treatment, we established a human induced pluripotent stem cells (iPSCs) from an AS patient carrying the mutation p.Asp563Gly of UBE3A gene at maternal 15q11.2-q13. The established patient-derived iPSC showed normal karyotype, expressed pluripotency markers, and had the capacity to differentiate into three germ layers.

Lateral flow immunoassay with peptide-functionalized gold nanoparticles for rapid detection of protein tyrosine phosphatase 1B.

In this work, a lateral flow immunoassay (LFIA) with peptide functionalized gold nanoparticles (termed as biotin-ppeptide-AuNPs) has been developed for rapid, semi-quantitative detection of PTP1B activity without using any sophisticated equipment. In this method, the anti-phosphotyrosine (anti-pY) monoclonal antibody and streptavidin were used as test line and control line, respectively. The biotin-ppeptide-AuNPs contain 10% biotinylated peptide ligand carry a motif SDGHEpYIYVDP with pY (phosphotyrosine) and 90% pentapeptide (CALNN) ligand, which are used as PTP1B substrates and LFIA labelling probes. The experimental results demonstrate that the as-proposed LFIA with biotin-ppeptide-AuNPs exhibits a wide linear range (from 50 ng/mL to 10 µg/mL), a relatively low limit of detection (LOD, 44 ng/mL), and good specificity. In addition, the LFIA with biotin-ppeptide-AuNPs has been successfully used to evaluate activity levels of PTP1B in four cell lysates and the detection results exhibit a consistent trend with that of commercial kit.

Enhancement of the Detection Performance of Paper-Based Analytical Devices by Nanomaterials.

Paper-based analytical devices (PADs), including lateral flow assays (LFAs), dipstick assays and microfluidic PADs (µPADs), have a great impact on the healthcare realm and environmental monitoring. This is especially evident in developing countries because PADs-based point-of-care testing (POCT) enables to rapidly determine various (bio)chemical analytes in a miniaturized, cost-effective and user-friendly manner. Low sensitivity and poor specificity are the main bottlenecks associated with PADs, which limit the entry of PADs into the real-life applications. The application of nanomaterials in PADs is showing great improvement in their detection performance in terms of sensitivity, selectivity and accuracy since the nanomaterials have unique physicochemical properties. In this review, the research progress on the nanomaterial-based PADs is summarized by highlighting representative recent publications. We mainly focus on the detection principles, the sensing mechanisms of how they work and applications in disease diagnosis, environmental monitoring and food safety management. In addition, the limitations and challenges associated with the development of nanomaterial-based PADs are discussed, and further directions in this research field are proposed.

Application of thermosensitive-hydrogel combined with dental pulp stem cells on the injured fallopian tube mucosa in an animal model.

Objectives: Fallopian tube (FT) injury is an important factor that can lead to tubal infertility. Stem-cell-based therapy shows great potential for the treatment of injured fallopian tube. However, little research has shown that mesenchymal stem cells (MSCs) can be used to treat fallopian tube damage by in situ injection. In this study, we in situ transplanted PF127 hydrogel encapsulating dental pulp stem cells (DPSCs) into the injured sites to promote the repair and regeneration of fallopian tube injury. Materials and methods: The properties of dental pulp stem cells were evaluated by flow cytometry, immunofluorescence analysis, and multi-differentiation detection. The immunomodulatory and angiogenic characteristics of dental pulp stem cells were analyzed on the basis of the detection of inflammatory factor expression and the formation of capillary-like structures, respectively. The biocompatibility of PF127 hydrogel was evaluated by using Live/Dead and CCK-8 assays. The effects of PF127 hydrogel containing dental pulp stem cells on the repair and regeneration of fallopian tube injury were evaluated by histological analysis [e.g., hematoxylin and eosin (H&E) and Masson's trichrome staining, TUNEL staining, immunofluorescence staining, and immunohistochemistry], Enzyme-linked immunosorbent assay (ELISA), and RT-PCR detections. Results: Dental pulp stem cells had MSC-like characteristics and great immunomodulatory and angiogenic properties. PF127 hydrogel had a thermosensitive feature and great cytocompatibility with dental pulp stem cells. In addition, our results indicated that PF127 hydrogel containing dental pulp stem cells could promote the repair and regeneration of fallopian tube damage by inhibiting cell apoptosis, stimulating the secretion of angiogenic factors, promoting cell proliferation, modulating the secretion of inflammatory factors, and restoring the secretion of epithelial cells. Conclusion: In this study, our results reported that in situ injection of PF127 hydrogel encapsulating dental pulp stem cells into the injured sites could provide an attractive strategy for the future treatment of fallopian tube injury in clinical settings.

The Peptide Functionalized Inorganic Nanoparticles for Cancer-Related Bioanalytical and Biomedical Applications.

In order to improve their bioapplications, inorganic nanoparticles (NPs) are usually functionalized with specific biomolecules. Peptides with short amino acid sequences have attracted great attention in the NP functionalization since they are easy to be synthesized on a large scale by the automatic synthesizer and can integrate various functionalities including specific biorecognition and therapeutic function into one sequence. Conjugation of peptides with NPs can generate novel theranostic/drug delivery nanosystems with active tumor targeting ability and efficient nanosensing platforms for sensitive detection of various analytes, such as heavy metallic ions and biomarkers. Massive studies demonstrate that applications of the peptide-NP bioconjugates can help to achieve the precise diagnosis and therapy of diseases. In particular, the peptide-NP bioconjugates show tremendous potential for development of effective anti-tumor nanomedicines. This review provides an overview of the effects of properties of peptide functionalized NPs on precise diagnostics and therapy of cancers through summarizing the recent publications on the applications of peptide-NP bioconjugates for biomarkers (antigens and enzymes) and carcinogens (e.g., heavy metallic ions) detection, drug delivery, and imaging-guided therapy. The current challenges and future prospects of the subject are also discussed.

Light-Trapping SERS Substrate with Regular Bioinspired Arrays for Detecting Trace Dyes.

Recently, few studies have focused on the light-trapping surface-enhanced Raman scattering (SERS) substrate combined with Si micropyramids and Ag (or Au). However, the Si micropyramids possess no ordered period, which not only affects the repeatability of the SERS signal but also affects the theoretical exploration. Here, the ordered micropyramids with strong light-trapping capability were fabricated by utilizing unconventional nanosphere lithography and anisotropy wet etching technique. Then, the Ag nanobowls were assembled on the ordered micropyramids to form the SERS substrate with bioinspired compound-eyes structure by utilizing the liquid-solid interface self-assembly and transfer technique. Especially, the evidence for the contribution of antireflective Si micropyramids to Raman enhancement was first presented. For this bioinspired SERS substrate, the lowest concentration of R6G that can be detected is 10-13 M with the level of a single molecule, and the relative standard deviation (RSD) is 3.68%. Meanwhile, the quantitative analysis and qualitative analysis can be realized. Especially, simultaneous trace detection of four common dyes (R6G, CV, MG, and MB) in food can be realized, suggesting that this SERS substrate will have a good application prospect in the field of optical sensors.

Silver-nanoparticle-grafted silicon nanocones for reproducible Raman detection of trace contaminants in complex liquid environments.

Super-hydrophobic delivery (SHD) is an efficient approach to enrich trace analytes into hot spot regions for ultrasensitive surface-enhanced Raman scattering (SERS) detection. In this article, we propose an efficient and simple method to prepare a highly-uniform SHD-SERS platform of high performance in trace detection, named as "silver-nanoparticle-grafted silicon nanocones" (termed AgNPs/SiNC) platform. It is fabricated via droplet-confined electroless deposition on the super-hydrophobic SiNC array. The AgNPs/SiNC platform allows trace analytes enriched into hot spots formed by AgNPs, leading to an excellent reproducibility and sensitivity. The relative standard deviation (RSD) for detecting R6G (10-7 M) is down to 4.70% and the lowest detection concentration for R6G is 10-14 M. Moreover, various contaminants in complex liquid environments, such as, crystal violet (10-9 M) in lake water, melamine (10-7 M) in liquid milk and methyl parathion (10-7 M) in tap water, can be detected using the SERS platform. This result demonstrates the great potential of the AgNPs/SiNC platform in the fields of food safety and environmental monitoring.

Development of a gold-nanorod-based lateral flow immunoassay for a fast and dual-modal detection of C-reactive protein in clinical plasma samples.

Fast and simple detection of C-reactive protein (CRP) is highly significant for the diagnosis and prognosis of inflammatory or infectious diseases. Lateral flow immunoassay has the advantages of rapid detection, simple operation and low cost, but it is usually limited by the quantitative ability and speed of data extraction. Herein, a gold-nanorod-based lateral flow immunoassay was developed to rapidly detect CRP by simultaneously monitoring the colorimetric and temperature signals. In this method, anti-CRP antibody-modified gold nanorods (GNRs) were designed as colorimetric and photothermal conversion probes. A mouse anti-CRP monoclonal antibody and goat anti-mouse IgG were used as test and control lines, respectively. Then, a lateral flow immunochromatographic strip was constructed by a sandwich-type method for detecting CRP by introducing antibody-modified GNRs, and this procedure needed less than 15 min. Finally, the detection signals can be directly observed by eyes and directly read using a thermal imager. The as-synthesized GNR showed high photothermal conversion efficiency (η = 39%) and strong localized surface plasmon resonance (LSPR) absorption. For CRP detection, the proposed immunochromatographic strip exhibited good specificity, high sensitivity, good linearity within the range of 50-10 000 ng mL-1 and a low limit of detection (LOD, 1.3 ng mL-1). This method was successfully applied for CRP detection in clinical plasma samples, and it correlated very well with the diagnostic kit of immunoturbidimetry (r = 0.96). The results indicated that the developed GNR-based immunochromatographic strip has immense potential for use as a rapid and cost-effective in vitro diagnostic kit.

Eliminating sweet spot in MALDI-MS with hydrophobic ordered structure as target for quantifying biomolecules.

In matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the analyte is usually distributed unevenly throughout the sample spot. The area with aggregated analyte molecules contributing abundant signal, is termed as "sweet spot", which results in poor detection reproducibility and makes it impossible to quantify analytes without internal standards. We proposed a strategy to eliminate sweet spot in MALDI-MS by using a hydrophobic ordered structure as target. The target is fabricated by creating a hydrophobic silicon nanopillar array and subsequently decorating it uniformly with poly(methyl methacrylate) nanodots for capturing analytes. The sweet spot is eliminated by distributing analyte molecules uniformly on this target, and then result in a uniform MS image, which demonstrates an ideal reproducibility. Finally, with the target assisted MALDI-MS as biosensor was suitable to analyze practical sample such as bacitracin A in milk. Horse heart myoglobin and, angiotensin III molecules can be quantified without internal standard using α-cyano-4-hydroxycinnamic acid as matrix. This biosensor presented good linearity, high salts tolerance and high signal-to-noise ratio (up to 271.8), even the 1 mol/L salt concentration. This strategy could provide an alternative for improving the performance of MALDI-MS.

Confining analyte droplets on visible Si pillars for improving reproducibility and sensitivity of SALDI-TOF MS.

We present a universal method to efficiently improve reproducibility and sensitivity of surface-assisted laser desorption/ionization time of flight mass spectrometry (SALDI-TOF MS). In this method, the Si pillar array with unique surface wettability is used as substrate for ionizing analyte. The Si pillar is fabricated based on the combination of photolithography and metal-assisted chemical etching, which is of hydrophilic top and hydrophobic bottom and side wall. Based on the surface wettability of the Si pillar, a droplet of an aqueous analyte solution can be confined on the top of the Si pillar. After evaporation of solvent, an analyte deposition spot is formed on the top of Si pillar. The visible size of the Si pillar allows the sample spot to be easily found. Meanwhile, the diameter of the Si pillar is smaller than that of the laser, allowing the observation of all analyte molecules under one laser shot. Therefore, the reproducibility and sensitivity are highly improved with this method, which allows for the quantitative analysis. Furthermore, this method is applicable for different analytes dissolved in water, including amino acids, dye molecules, polypeptides, and polymers. The application of this substrate is demonstrated by analyzing real samples at low concentration. It should be a promising method for sensitive and reproducible detection for SALDI-TOF MS. Graphical abstract ᅟ.

Using Recombinant Human Collagen With Basic Fibroblast Growth Factor to Provide a Simulated Extracellular Matrix Microenvironment for the Revascularization and Attachment of Islets to the Transplantation Region.

Islet transplantation is considered a potential therapeutic option to reverse diabetes. The pancreatic basement membrane contains a variety of extracellular matrix (ECM) proteins. The abundant ECM is essential for the survival of transplanted islets. However, the ECM proteins necessary for maintaining islet vascularization and innervation are impaired by enzymatic digestion in the isolation process before islet transplantation, leading to destruction of islet microvessels. These are the primary concern and major barrier for long-term islet survival and function. Thus, it is crucial to create an appropriate microenvironment for improving revascularization and islet function to achieve better transplantation outcome. Given the importance of the presence of ECM proteins for islets, we introduce recombinant human collagen (RHC) to construct a simulated ECM microenvironment. To accelerate revascularization and reduce islet injury, we add basic fibroblast growth factor (bFGF) to RHC, a growth factor that has been shown to promote angiogenesis. In order to verify the outcome, islets were treated with RHC combination containing bFGF and then implanted into kidney capsule in type 1 diabetic mouse models. After transplantation, 30-day-long monitoring displayed that 16 mg-60 ng RHC-bFGF group could serve as superior transplantation outcome. It reversed the hyperglycemia condition in host rapidly, and the OGTT (oral glucose tolerance test) showed a similar pattern with the control group. Histological assessment showed that 16 mg-60 ng RHC-bFGF group attenuated apoptosis, promoted cellular proliferation, triggered vascularization, and inhibited inflammation reaction. In summary, this work demonstrates that application of 16 mg-60 ng RHC-bFGF and islets composite enhance the islet survival, function, and long-term transplantation efficiency.

Ag nanoparticles/ZnO nanorods for highly sensitive detection of small molecules with laser desorption/ionization mass spectrometry.

In this report, a matrix-free method for high-efficiency detection of small molecules with a Ag nanoparticles/ZnO nanorods (Ag NPs/ZnO NRs) substrate as platform for surface-assisted laser desorption/ionization mass spectrometry (SALDI MS) was carried out for the first time. Ag NPs were decorated on the ZnO NRs substrate by vapor deposition. The charge separation efficiency of composite substrate was optimized by regulating the amount of evaporated Ag NPs. The excellent electron-hole separation efficiency of the Ag NPs/ZnO NRs was measured by surface photovoltage (SPV). For the same analytes, the Ag NPs/ZnO NRs substrate in negative ion mode possesses higher signal intensity and lower limit of detection (LOD). The LOD of Arginine on the Ag NPs/ZnO NRs composite substrate is only 1.0 × 10-15 M, which is 2 orders of magnitude lower than that on the ZnO NRs substrate. The other 3 amino acids (Tryptophan, Tyrosine and Lysine) could be also detected, the Ag NPs/ZnO NRs substrate showed better sensitivity and lower LODs. It indicates that the charge separation of the ZnO NRs can promote the accumulation of electrons on Ag NPs surface, which enhances laser desorption/ionization (LDI) efficiency in negative ion mode. Finally, the application of this substrate was demonstrated by analyzing the real samples, including malachite green in lake water, methadone in urine, verapamil in serum and Bradykinin 1-7 in serum, it performs highly sensitivity and linear correlation for actual samples.

Superhydrophobic candle soot/PDMS substrate for one-step enrichment and desalting of peptides in MALDI MS analysis.

Superhydrophobic substrate is applied in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) detection due to its confinement effect. The weak interaction of superhydrophobic surface with water/salts makes it potential in one-step enrichment and desalting of peptide in MALDI MS analysis. We fabricate a superhydrophobic substrate by spin-coating poly(dimethyl siloxane) (PDMS) on a candle soot layer. On this substrate, the peptide analytes can be confined and enriched in a small area due to the confinement effect and its strong hydrophobic interactions with PDMS. Meanwhile, the desalting can be easily realized by removing the residual solution after the absorption of analyst molecules due to the weak interaction between water/salt contaminants and the superhydrophobic surface. Using this substrate, angiotensin III (Ang III) in the presence of salt with high concentration (2 M or saturated) can be analyzed, and the peptide sequence coverage of 10 µg/mL myoglobin (MYO) and bovine serum albumin (BSA) digests is enhanced to 51% and 26%, which is 37% and 21% analyzed with the commercial ZipTipC18 pipette tips. The LOD of bacitracin A (Bac A) in milk with this substrate is 100 pM and nearly 360 times lower than the LOD of standard testing method. This substrate has potential practical applications in proteomics research and actual sample analysis.

Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core-shell nanoparticles targeting the heterogeneous tumor cells of glioma.

Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core-shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of -30.5 mV, while its core-shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats.

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

Enhancing reproducibility of SALDI MS detection by concentrating analytes within laser spot.

Surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI TOF MS) has become one of the most important analytical methods due to its less interference at low molecular weight range. However, it is still a challenge to obtain a good reproducibility of SALDI TOF MS because of the inhomogeneous distribution of analyte molecules induced by coffee ring effect. We propose a universal and reliable method to eliminate the coffee ring effect by concentrating all the analyte molecules within the laser spot. This method exhibits an excellent reproducibility of spot-to-spot and substrate-to-substrate, and the relative standard deviations (RSDs) for different concentrations are lower than 12.6%. It also performs good linear dependency (R2 > 0.98) in the log-log plot with the concentration range of 1nM to 1µM, and the limit of detection for R6G is down to 1fmol.

Glioma-Targeted Delivery of a Theranostic Liposome Integrated with Quantum Dots, Superparamagnetic Iron Oxide, and Cilengitide for Dual-Imaging Guiding Cancer Surgery.

Herein, a theranostic liposome (QSC-Lip) integrated with superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into one platform is constructed to target glioma under magnetic targeting (MT) for guiding surgical resection of glioma. Transmission electron microscopy and X-ray photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs in liposome. Besides, CGT is also effectively encapsulated into the liposome with an encapsulation efficiency of ∼88.9%. QSC-Lip exhibits a diameter of 100 ± 1.24 nm, zeta potential of -17.10 ± 0.11 mV, and good stability in several mediums. Moreover, each cargo shows a biphasic release pattern from QSC-Lip, a rapid initial release within initial 10 h followed by a sustained release. Cellular uptake of QSC-Lip is significantly enhanced by C6 cells under MT. In vivo dual-imaging studies show that QSC-Lip not only produces an obvious negative-contrast enhancement effect on glioma by magnetic resonance imaging but also makes tumor emitting fluorescence under MT. The dual-imaging of QSC-Lip guides the accurate resection of glioma by surgery. Besides, CGT is also specifically distributed to glioma after administration of QSC-Lip under MT, resulting in an effective inhibition of tumors. The integrated liposome may be a potential carrier for theranostics of tumor.