Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Low-to-moderate fluoride exposure in relation to overweight and obesity among school-age children in China.

High fluoride exposure has been related to harmful health effects, but the impacts of low-to-moderate fluoride on child growth and obesity-related outcomes remain unclear. We performed a large-scale cross-sectional study to examine the association between low-to-moderate fluoride in drinking water and anthropometric measures among Chinese school-age children. We recruited 2430 resident children 7-13 years of age, randomly from low-to-moderate fluorosis areas of Baodi District in Tianjin, China. We analyzed the fluoride contents in drinking water and urine samples using the national standardized ion selective electrode method. Multivariable linear and logistic analyses were used to assess the relationships between fluoride exposure and age- and sex-standardized height, weight and body mass index (BMI) z-scores, and childhood overweight/obesity (BMI z-score > 1). In adjusted models, each log unit (roughly 10-fold) increase in urinary fluoride concentration was associated with a 0.136 unit increase in weight z-score (95% CI: 0.039, 0.233), a 0.186 unit increase in BMI z-score (95% CI: 0.058, 0.314), and a 1.304-fold increased odds of overweight/obesity (95% CI: 1.062, 1.602). These associations were stronger in girls than in boys (Pinteraction = 0.016), and children of fathers with lower education levels were more vulnerable to fluoride (Pinteraction = 0.056). Each log unit (roughly 10-fold) increase in water fluoride concentration was associated with a 0.129 unit increase in height z-score (95% CI: 0.005, 0.254), but not with other anthropometric measures. Our results suggest low-to-moderate fluoride exposure is associated with overweight and obesity in children. Gender and paternal education level may modify the relationship.

Three-Dimensional Evaluation on the Effect of Maxillary Dentition Distalization With Miniscrews Implanted in the Infrazygomatic Crest.

OBJECTIVE: To evaluate the effect of the maxillary dentition distalization with miniscrews implanted in the infrazygomatic (IZ) crest with 3D reconstruction module from cone-beam computed tomography (CBCT). METHODS: Twenty patients who previously underwent dentition distalization treatment with miniscrews were recruited. A total of 40 images were obtained using CBCT, taken immediately before placement of the miniscrew anchorage and at the end of distalization. The 3D-line measurements were recorded to monitor dental changes. RESULTS: There was significant movement of maxillary dentition before and after treatment with miniscrews. The miniscrews induced maxillary dentition distalization and corrected Class II relationship in 8 months on average. The incisors were retracted 4.3 mm and extruded 3.8 mm at the crown on average. The crown of canines showed 3.7 mm of distalization and the width increased by 3.1 mm averagely. The mesial buccal cusp of first molars' crowns showed 3.5-mm distalization and 2.1-mm intrusion, and the width increased by 5.0 mm averagely. The distal buccal cusp of first molars' crowns showed 2.8-mm distalization and 3.7-mm intrusion, and the width increased by 6.2 mm averagely. CONCLUSIONS: The anchorage of miniscrews implanted in the IZ crest is an efficient device for maxillary dentition distalization.

Effects of different oxidants on the behaviour of microplastic hetero-aggregates.

Microplastic hetero-aggregates are stable forms of microplastics in the aqueous environment. However, when disinfecting water containing microplastic hetero-aggregates, the response of them in water to different oxidizing agents and the effect on water quality have not been reported. Our results showed that Ca(ClO)2, K2S2O8, and sodium percarbonate (SPC) treatment could lead to the disaggregation of microplastic hetero-aggregates as well as a rise in cell membrane permeability, which caused a large amount of organic matter to be released. When the amount of oxidant dosing is insufficient, the oxidant cannot completely degrade the released organic matter, resulting in DOC, DTN, DTP and other indicators being higher than before oxidation, thus causing secondary pollution of the water body. In comparison, K2FeO4 can purify the water body stably without destroying the microplastic hetero-aggregates, but it only weakly inhibits the toxic cyanobacteria Microcystis and Pseudanabaena, which may cause cyanobacterial bloom as well as algal toxin and odorant contamination in practical application. Compared with the other oxidizers, K2S2O8 provides better inhibition of toxic cyanobacteria and has better ecological safety. Therefore, when treating microplastic-containing water bodies, we should consider both water purification and ecological safety, and select appropriate oxidant types and dosages to optimize the water treatment.

A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

Neural Progenitor Cell-Mediated Magnetic Nanoparticles for Magnetic Resonance Imaging and Photothermal Therapy of Glioma.

Glioma is the most common primary malignant tumor in the brain. The diagnostic accuracy and treatment efficiency of glioma are facing great challenges due to the presence of the blood-brain barrier (BBB) and the high infiltration of glioma. There is an urgent need to explore the combination of diagnostic and therapeutic approaches to achieve a more accurate diagnosis, as well as guidance before and after surgery. In this work, we induced human induction of pluripotent stem cell into neural progenitor cells (NPCs) and synthesized nanoprobes labeled with enhanced green fluorescent protein (EGFP, abbreviated as MFe3O4-labeled EGFP-NPCs) for photothermal therapy. Nanoprobes carried by NPCs can effectively penetrate the BBB and target glioma for the purpose of magnetic resonance imaging and guiding surgery. More importantly, MFe3O4-labeled EGFP-NPCs can effectively induce local photothermal therapy, conduct preoperative tumor therapy, and inhibit the recurrence of postoperative glioma. This work shows that MFe3O4-labeled EGFP-NPCs is a promising nanoplatform for glioma diagnosis, accurate imaging-guided surgery, and effective photothermal therapy.

The establishment of a novel upper cervical complex fracture classification system.

BACKGROUND CONTEXT: Upper cervical complex fractures are associated with high rates of neurological damage and mortality. The Dickman's classification is widely used in the diagnosis of upper cervical complex fractures. However, it falls short of covering the full spectrum of complex fractures. This limitation hinders effective diagnosis and treatment of these injuries. PURPOSE: To address the diagnostic gap in upper cervical complex fractures, the study introduces a novel classification system for these injuries, assessing its reliability and usability. STUDY DESIGN: Proposal of a new classification system for upper cervical complex fractures. PATIENT SAMPLE: The study comprised the clinical data of 242 patients with upper cervical complex fractures, including 32 patients treated at our hospital, along with an additional 210 cases from the literature. OUTCOME MEASURES: The inter-observer and intra-observer reliability (kappa coefficient, κ) of this classification system were investigated by 3 spine surgeons. The 3 researchers independently re-evaluated the upper cervical complex fracture classification system 3 months later. METHODS: The proposed classification categorizes upper cervical complex fractures into 3 main types: Type I combines odontoid and Hangman's fractures into 2 subtypes; Type II merges C1 with odontoid/Hangman's fractures into 3 subtypes; and Type III encompasses a combination of C1, odontoid, and Hangman's fractures, divided into 2 subtypes. Meanwhile, a questionnaire was administered in 15 assessors to evaluate the system's ease of use and clinical applicability. RESULTS: A total of 45 cases (18.6%) unclassifiable by Dickman's classification were successfully categorized using our system. The mean κ value of inter-observer reliability was 0.783, indicating substantial reliability. The mean κ value of intra-observer reliability was 0.862, indicating almost perfect reliability. Meanwhile, thirteen assessors (87.7%) stated that the classification system is easy to remember, easy to apply, and they expressed intentions to apply it in clinical practice in the future. CONCLUSIONS: This system not only offers high confidence and reproducibility but also serves as a precise guide for clinicians in formulating treatment plans. Future prospective applications are warranted to further evaluate this classification system.

PEGylated FePt@Fe2O3 core-shell magnetic nanoparticles: potential theranostic applications and in vivo toxicity studies.

Herein, we develop FePt@Fe2O3 core-shell magnetic nanoparticles as a T2 magnetic resonance (MR) imaging contrast agent as well as a drug carrier for potential cancer theranostic applications. The FePt@Fe2O3 core-shell nanoparticles are synthesized and then functionalized with polyethylene glycol (PEG). Folic acid (FA) is conjugated on the surface of FePt@Fe2O3-PEG nanoparticles for effective targeting of folate receptor (FR)-positive tumor cells. A chemotherapy drug, doxorubicin (DOX), is then loaded onto those nanoparticles via hydrophobic physical adsorption, for targeted intracellular drug delivery and selective cancer cell killing. We then use those FePt@Fe2O3-PEG nanoparticles for in vivo MR imaging, observing obvious tumor MR contrasts, which resulted from both passive tumor accumulation and active tumor targeting of nanoparticles. Moreover, both in vitro and in vivo studies uncover no obvious toxicity for FePt@Fe2O3-PEG nanoparticles. Therefore, our PEGylated FePt@Fe2O3 core-shell nanoparticles could serve as a promising multifunctional theranostic nano-platform in imaging guided cancer therapy. FROM THE CLINICAL EDITOR: In this study of PEGylated FePt@Fe2O3 core-shell magnetic nanoparticles, both therapeutic and diagnostic applications are demonstrated. Folic acid surface-conjugation resulted in uptake by folate receptor positive cancer cells, the iron oxide particles enabled MRI imaging using T2* weighted sequences, and the absorbed doxorubicin provided treatment effects in this model. Similar multi-modality approaches will hopefully find their way to clinical applications in the near future.

X-band TE101 rectangular aperture cavity for in vivo EPR tooth dosimetry after radiation emergency.

The TE101 mode rectangle EPR cavity was newly developed to achieve X-band in vivo EPR tooth dosimetry for the rescue of nuclear emergency. An aperture for sample detection was opened on the cavity's surface. Its characteristics were evaluated by measuring DPPH and intact human incisor samples. Remarkable radiation induced signal from EPR spectrum of 1Gy-8Gy irradiated teeth was observed. In vivo measurements of rat was performed to verify its application for in vivo tooth dosimetry.

Ultrasmall Oxygen-Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue-penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging-guided enhanced SDT against cancer. As-made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX -PEG nanoparticles exhibit highly efficient US-triggered production of 1 O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen-deficient structure of MnWOX serves as an electron trap site to prevent electron-hole recombination. The glutathione depletion capability of MnWOX -PEG can also further favor SDT-triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX -PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX -PEG can be metabolized by the mouse body without any long-term toxicity. Herein, a new type of sono-sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Recombinant fimbriae protein of Porphyromonas gingivalis induces an inflammatory response via the TLR4/NF­κB signaling pathway in human peripheral blood mononuclear cells.

Porphyromonas gingivalis (P. gingivalis) is a periodontal pathogen that may accumulate with other organisms in subgingival plaque biofilms and is associated with periodontal disease. P. gingivalis fimbriae (FimA) is a filamentous structure on the surface of bacteria that is closely associated with bacterial adhesion to and colonization of host tissues, and serves an essential role in biofilm formation. The present study aimed to construct P. gingivalis FimA prokaryotic expression plasmids, purify a FimA fusion protein and explore the effect of a recombinant FimA protein on the inflammatory response in human peripheral blood mononuclear cells (PBMCs). P. gingivalis FimA prokaryotic expression plasmids were constructed by gene cloning and recombination technology. SDS­PAGE was used to evaluate the purified recombinant FimA protein. The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll­like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK­8 assays and ELISAs, respectively. The expression levels of TLR4, nuclear factor kappa­light­chain­enhancer of activated B cells (NF­κB) and myeloid differentiation primary response 88 (MyD88) in PBMCs were detected by western blot analysis and reverse transcription quantitative polymerase chain reaction. A FimA fusion protein with high purity was obtained. FimA fusion protein treatment significantly increased PBMC proliferation and promoted the release of tumor necrosis factor­α (TNF­α), interleukin (IL)­6, matrix metalloproteinase (MMP)­8 and MMP­9 in PBMCs. TLR4 interference reversed the effects of the FimA fusion protein on PBMC proliferation and inflammatory cytokine release. The expression levels of TLR4, NF­κB and MyD88 in PBMCs were significantly increased following treatment with the FimA fusion protein, while the expression levels of these genes at the mRNA and protein levels decreased significantly in PBMCs following FimA fusion protein treatment and TLR4 interference. The FimA fusion protein increased PBMC proliferation and promoted the release of the inflammatory cytokines TNF­α, IL­6, MMP­8 and MMP­9 via the TLR4/NF­κB signaling pathway. FimA may serve as a promising therapeutic strategy for periodontal disease.

[Dynamic changes of B7-H1 expression on mDCs and T cells in chronic hepatitis B patients treated with PEG-IFN alpha-2a].

OBJECTIVE: To study the dynamic changes of B7-H1 expression on myeloid dendritic cells (mDCs) and T cells in chronic hepatitis B (CHB) patients undergoing PEG-IFN alpha-2a therapy, and to analyze the association of the changes with the efficiency of interferon-alpha therapy. METHODS: Expressions of B7-H1 on mDCs and T cells in 14 patients with chronic HBV infection, including 6 responders and 8 non-responders to the antiviral therapy, were monitored by using flow cytometric analysis. Peripheral blood mononuclear cells from patients were incubated in vitro and the numbers of IFN-gamma-producing antigen-specific T cells were measured using ELISPOT assay. RESULTS: B7-H1 expressions by mDCs, CD4+ T cells and CD8+ T cells were all significantly upregulated at 4 weeks after starting PEG-IFN alpha-2a therapy. After this time point, B7-H1 expressions persistently decreased in the responders to the antiviral treatment, while non-responders maintained high levels of B7-H1 expression. In addition, the frequency of HBV-specific IFN-gamma-producing T cells significantly increased in the responders, but significantly decreased in the non-responders. Blocking the B7-H1 signal pathway increased the numbers of HBV-specific IFN-gamma-producing T cells in both the responders and non-responders. CONCLUSION: Dynamic changes of B7-H1 expression by mDCs and T cells in CHB patients undergoing PEG-IFN alpha-2a therapy can predict the efficiency of the therapy. Blocking the B7-H1 inhibitory pathway likely enhances the antiviral cellular T-cell responses.

In vitro effect of Porphyromonas gingivalis combined with influenza A virus on respiratory epithelial cells.

OBJECTIVE: Respiratory epithelial cells are the first natural barrier against bacteria and viruses; hence, the interactions among epithelial cells, bacteria, and viruses are associated with disease occurrence and development. The effect of co-infection by P. gingivalis and influenza A virus (IAV) on respiratory epithelial cells remains unknown. The aim of this study was to analyze in vitro cell viability and apoptosis rates in respiratory epithelial A549 cells infected with P. gingivalis or IAV alone, or a combination of both pathogens. DESIGN: A549 cells were first divided into a control group, a P. gingivalis group, an IAV group, and a P. gingivalis + IAV group, to examine cell viability and apoptosis rates, the levels of microtubule associated protein 1 light chain 3 B (LC3-II), microtubule associated protein 1 light chain 3A (LC3-I), and sequestosome 1 (P62), and the formation of autophagosomes. The autophagy inhibitor, 3-methyladenine (3MA), was used to assess autophagy and apoptosis in A549 cells infected with P. gingivalis or IAV. RESULTS: An MTT assay revealed that cell viability was significantly lower in the IAV group than in the P. gingivalis + IAV group (P < 0.05). Flow cytometry indicated that the apoptosis rate was significantly higher in the IAV group than in the P. gingivalis + IAV group (P < 0.05). The fluorescence levels of GFP-LC3 increased significantly, the LC3-II/LC3-I ratio was significantly higher, and the P62 protein levels were statistically lower in the P. gingivalis + IAV group compared with the IAV group (all P < 0.05). Western blotting revealed that the LC3- II/LC3-I ratio was significantly lower, and caspase-3 levels were significantly higher in the 3MA + P. gingivalis + IAV group compared to the P. gingivalis + IAV group (all P < 0.05). CONCLUSION: In vitro studies showed that infection by P. gingivalis combined with IAV temporarily inhibited apoptosis in respiratory epithelial cells, and this may be related to the initiation of autophagy.

Strontium incorporation improves the bone-forming ability of scaffolds derived from porcine bone.

Although heterogeneous bone scaffolds have shown potential in bone defect repair, their capability of aiding bone regeneration need to be further enhanced. Strontium, one important trace element in bone, has a well-known favorable effect on bone repair. Here a strontium containing scaffold (CPB/PCL/Sr) based on superficially porous calcined porcine bone (CPB) was obtained straightforwardly by sequential coating of SrCl2 and polycaprolactone (PCL). The basic characterization revealed that PCL coating could simultaneously improve the mechanical properties and, more importantly, restrain strontium release. Moreover, in vitro behaviors of human MSCs on CPB, CPB/PCL, and CPB/PCL/Sr were studied in detail. The comprehensive results of proliferation, osteogenic gene expression, ALP staining, and ALP activity demonstrated that PCL coating slightly impaired the bone repair potential of CPB. In contrast, CPB/PCL/Sr better supported the osteogenic differentiation of MSCs than CPB，highlighting the role of strontium. The in vivo test confirmed a better new bone formation of CPB/PCL/Sr than CPB and CPB/PCL. These results verified the superiority of incorporating strontium to improve the bone-forming ability of CPB, offering a promising alternative for bone defect repair.

Threshold effects of moderately excessive fluoride exposure on children's health: A potential association between dental fluorosis and loss of excellent intelligence.

BACKGROUND: Excessive fluoride exposure is associated with adverse health outcomes, but little is known of the effects of moderately chronic fluoride exposure on children's health. OBJECTIVES: We conducted a cross-sectional study to explore the health impact of moderately excessive fluoride in drinking water. METHODS: We recruited 2886 resident children, aged 7 to 13 years, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. The fluoride levels in drinking water and urine were measured using the national standardized ion selective electrode method. We examined the dose-response effects of low-to-moderate fluoride exposure on dental fluorosis (DF) and intelligence quotient (IQ), and evaluated the potential relationships between DF grades and intelligence levels using piecewise linear regression and multiple logistic regression, respectively. RESULTS: The adjusted odds ratios (ORs) of DF were 2.24 (95% confidence interval [CI]: 2.02 to 2.48) for every 0.1 mg/L increment in the water fluoride concentration in the range of 0.80 to 1.50 mg/L, and 2.61 (95% CI: 2.32 to 2.93) for every 0.5 mg/L increment in the urinary fluoride level up to 1.80 mg/L. Every 0.5 mg/L increment in the water fluoride level was associated with a reduction of 4.29 in the IQ score (95% CI: -8.09 to -0.48) in the range of 3.40 to 3.90 mg/L, and a decreased probability of developing excellent intelligence (IQ ≥ 130, OR = 0.60, 95% CI: 0.47 to 0.77) in the range of 0.20-1.40 mg/L, respectively. Every 0.5 mg/L increment in the urinary fluoride level was related to a decrease of 2.67 in the IQ scores (95% CI: -4.67 to -0.68) between 1.60 mg/L to 2.50 mg/L. Excellent intelligence decreased by 51% in children with higher urinary fluoride, and by 30% with each degree increment of DF. CONCLUSIONS: Our study suggests threshold and saturation effects of moderately excessive fluoride exposure on DF and intelligence loss in children, and a potential association between DF and the loss of excellent intelligence.

Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-guided Cancer Combination Therapy.

Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects. Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy. In this system, ICG acts as a photothermal agent, which shows red-shifted near-infrared (NIR) absorbance and enhanced photostability compared with free ICG. DOX, a model chemotherapy drug, is then loaded onto the surface of PDA-ICG-PEG with high efficiency. With Mn(2+) ions intrinsically chelated, PDA-ICG-PEG/DOX(Mn) is able to offer contrast under T1-weighted magnetic resonance (MR) imaging. In a mouse tumor model, the MR imaging-guided combined chemo- & photothermal therapy achieves a remarkable synergistic therapeutic effect compared with the respective single treatment modality. This work demonstrates that PDA nanoparticles could serve as a versatile molecular loading platform for MR imaging guided combined chemo- & photothermal therapy with minimal side effects, showing great potential for cancer theranostics.

Nanoscale Metal-Organic Particles with Rapid Clearance for Magnetic Resonance Imaging-Guided Photothermal Therapy.

Nanoscale metal-organic particles (NMOPs) are constructed from metal ions and organic bridging ligands via the self-assembly process. Herein, we fabricate NMOPs composed of Mn(2+) and a near-infrared (NIR) dye, IR825, obtaining Mn-IR825 NMOPs, which are then coated with a shell of polydopamine (PDA) and further functionalized with polyethylene glycol (PEG). While Mn(2+) in such Mn-IR825@PDA-PEG NMOPs offers strong contrast in T1-weighted magnetic resonance (MR) imaging, IR825 with strong NIR optical absorbance shows efficient photothermal conversion with great photostability in the NMOP structure. Upon intravenous injection, Mn-IR825@PDA-PEG shows efficient tumor homing together with rapid renal excretion behaviors, as revealed by MR imaging and confirmed by biodistribution measurement. Notably, when irradiated with an 808 nm laser, tumors on mice with Mn-IR825@PDA-PEG injection are completely eliminated without recurrence within 60 days, demonstrating the high efficacy of photothermal therapy with this agent. This study demonstrates the use of NMOPs as a potential photothermal agent, which features excellent tumor-targeted imaging and therapeutic functions, together with rapid renal excretion behavior, the latter of which would be particularly important for future clinical translation of nanomedicine.

Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing.

Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.

PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy.

Magnetic targeting that utilizes a magnetic field to specifically delivery theranostic agents to targeted tumor regions can greatly improve the cancer treatment efficiency. Herein, we load chlorin e6 (Ce6), a widely used PS molecule in PDT, on polyethylene glycol (PEG) functionalized iron oxide nanoclusters (IONCs), obtaining IONC-PEG-Ce6 as a theranostic agent for dual-mode imaging guided and magnetic-targeting enhanced in vivo PDT. Interestingly, after being loaded on PEGylated IONCs, the absorbance/excitation peak of Ce6 shows an obvious red-shift from ~650 nm to ~700 nm, which locates in the NIR region with improved tissue penetration. Without noticeable dark toxicity, Ce6 loaded IONC-PEG (IONC-PEG-Ce6) exhibits significantly accelerated cellular uptake compared with free Ce6, and thus offers greatly improved in vitro photodynamic cancer cell killing efficiency under a low-power light exposure. After demonstrating the magnetic field (MF) enhanced PDT using IONC-PEG-Ce6, we then further test this concept in animal experiments. Owing to the strong magnetism of IONCs and the long blood-circulation time offered by the condensed PEG coating, IONC-PEG-Ce6 shows strong MF-induced tumor homing ability, as evidenced by in vivo dual modal optical and magnetic resonance (MR) imaging. In vivo PDT experiment based magnetic tumor targeting using IONC-PEG-Ce6 is finally carried out, achieving high therapeutic efficacy with dramatically delayed tumor growth after just a single injection and the MF-enhanced photodynamic treatment. Considering the biodegradability and non-toxicity of iron oxide, our IONC-PEG-Ce6 presented in this work may be a useful multifunctional agent promising in photodynamic cancer treatment under magnetic targeting.