Dual-functional Nanoparticles Research Articles

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

Coordination-Polymer-Derived Cu-CoO/C Nanocomposite Used in Fenton-like Reaction to Achieve Efficient Degradation of Organic Compounds.

In this paper, carbon-matrix-supported copper (Cu) and cobaltous oxide (CoO) nanoparticles were obtained by using coordination polymers (CPs) as a precursor. The aqueous solutions of copper methacrylate (CuMA) and cobalt methacrylate (CoMA) were preferentially prepared, which were then mixed with anhydrous ethanol to fabricate dual metal ion coordination polymers (CuMA/CoMA). After calcination under an argon atmosphere, the Cu-CoO/C nanocomposite was obtained. Scanning electron microscope (SEM) and transmission electron microscope (TEM) showed that the material has banded morphology, and the dual functional nanoparticles were highly dispersed in the carbon matrix. The prepared material was used in a heterogeneous Fenton-like reaction, with the aim of replacing traditional ferric catalysts to solve pH constraints and the mass production of ferric slime. The obtained nanocomposite showed excellent catalytic performance on the degradation of methylene blue (MB) at near-neutral conditions; the discoloration efficiency is about 98.5% within 50 min in the presence of 0.15 mmol/mL H2O2 and 0.5 mg/mL catalyst. And good reusability was verified via eight cycles. The plausible pathway for MB discoloration and the possible catalytic mechanism was also proposed.

Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer.

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Preparation and in Vitro Property Research of Cholic Acid Nanoparticles with Dual-functions of Hemostasis and Antibacterial.

Hemorrhage control and anti-infection play a crucial role in promoting wound healing in trauma-related injuries. This study aimed to prepare nanoparticles with dual functions of hemostasis and antibacterial properties. The dual-functional nanoparticles (CDCA-PLL NPs) were developed using a self-assembly method based on the electrostatic forces between poly-L-lysine (PLL) and Chenodeoxycholic acid (CDCA). The physicochemical properties, hemostatic properties, and antibacterial activities were investigated. The prepared nanoparticles displayed a spherical structure, exhibiting a high drug loading capacity, encapsulation efficiency, and good stability. The CDCA-PLL NPs could reduce the hemolysis caused by PLL and promote the proliferation of human fibroblasts, indicating excellent biosafety. Moreover, CDCA-PLL NPs demonstrated a shorter in vivo hemostasis time and reduced blood loss in mouse tail vein hemorrhage, femoral vein hemorrhage, femoral artery hemorrhage, and liver hemorrhage models. Also, CDCA-PLL NPs showed excellent antibacterial efficacy against E. coli and S. aureus. CDCA-PLL NPs have great potential to be extensively applied as a hemostatic and antibacterial agent in various clinical conditions.

Isorhamnetin and anti-PD-L1 antibody dual-functional mesoporous silica nanoparticles improve tumor immune microenvironment and inhibit YY1-mediated tumor progression

BackgroundThe immune checkpoint inhibitor (ICI) anti-PD-L1 monoclonal antibody can inhibit the progress of hepatocellular carcinoma (HCC). Epithelial–mesenchymal transformation (EMT) can promote tumor migration and the formation of immune-suppression microenvironment, which affects the therapeutic effect of ICI. Yin-yang-1 (YY1) is an important transcription factor regulating proliferation, migration and EMT of tumor cells. This work proposed a drug-development strategy that combined the regulation of YY1-mediated tumor progression with ICIs for the treatment of HCC.MethodsWe first studied the proteins that regulated YY1 expression by using pull-down, co-immunoprecipitation, and duo-link assay. The active compound regulating YY1 content was screened by virtual screening and cell-function assay. Isorhamnetin (ISO) and anti-PD-L1 antibody dual-functional mesoporous silica nanoparticles (HMSN-ISO@ProA-PD-L1 Ab) were prepared as an antitumor drug to play a synergistic anti-tumor role.ResultsYY1 can specifically bind with the deubiquitination enzyme USP7. USP7 can prevent YY1 from ubiquitin-dependent degradation and stabilize YY1 expression, which can promote the proliferation, migration and EMT of HCC cells. Isorhamnetin (ISO) were screened out, which can target USP7 and promote YY1 ubiquitin-dependent degradation. The cell experiments revealed that the HMSN-ISO@ProA-PD-L1 Ab nanoparticles can specifically target tumor cells and play a role in the controlled release of ISO. HMSN-ISO@ProA-PD-L1 Ab nanoparticles inhibited the growth of Hepa1-6 transplanted tumors and the effect was better than that of PD-L1 Ab treatment group and ISO treatment group. HMSN-ISO@ProA-PD-L1 Ab nanoparticles also exerted a promising effect on reducing MDSC content in the tumor microenvironment and promoting T-cell infiltration in tumors.ConclusionsThe isorhamnetin and anti-PD-L1 antibody dual-functional nanoparticles can improve tumor immune microenvironment and inhibit YY1-mediated tumor progression. This study demonstrated the possibility of HCC treatment strategies based on inhibiting USP7-mediated YY1 deubiquitination combined with anti-PD-L1 monoclonal Ab.

NIR‐triggered Synergetic Photothermal and Chemotherapy Cancer Treatment Based on SiO2@Au@SiO2@QDs‐DOX Composite Structural Particles

AbstractThis paper reports the synthesis of multi‐layer SiO2@Au@SiO2@QDs nanoparticles with a dual‐functionality of simultaneous heating and temperature sensing and their applications to in vitro chemo‐thermal therapy. The heating is activated by a NIR‐light through resonance excitation of surface plasma while in‐situ thermal sensing is accomplished by the QDs photoluminescent (PL) effect. These dual function nanoparticles are used as a drug carrier for in vitro chemotherapy‐photothermal co‐treatment for malignant cells. A comparative study of drug release profiles was performed with and without 808 nm laser irradiation. The drug release rate was accelerated by a rise of temperature, which is induced by plasmonic heat generation associated with Au nanoshells; while the temperature change is monitored by the QD nanoparticles at the same time. The results showed that SiO2@Au@SiO2@QDs‐DOX platform enabled the combination of local specific chemotherapy with external near‐infrared (NIR) photothermal therapy and significantly improved the efficacy of cancer treatment. This combined treatment demonstrated synergistic chemotherapeutic‐thermal effects compared to chemotherapy or photothermal therapy alone, resulting in higher efficacy.

Evaluation of a Tumor-Targeting Oligosaccharide Nanosystem in BNCT on an Orthotopic Hepatocellular Carcinoma Model.

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.

Bioinspired surface functionalization of biodegradable mesoporous silica nanoparticles for enhanced lubrication and drug release

Osteoarthritis is associated with the significantly increased friction of the joint, which results in progressive and irreversible damage to the articular cartilage. A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis. In the present study, bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages, a biomimetic self-adhesive dopamine methacrylamide—poly(2-methacryloyloxyethyl phosphorylcholine) (DMA—MPC) copolymer was designed and synthesized via free radical polymerization. The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles (bMSNs) by the dip-coating method to prepare the dual-functional nanoparticles (bMSNs@DMA—MPC), which were evaluated using a series of surface characterizations including the transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectrum, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), etc. The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug, i.e., diclofenac sodium (DS). In addition, the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d. Furthermore, the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). In summary, the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.

Surface fabrication of magnetic core-shell silica nanoparticles with perylene diimide as a fluorescent dye for nucleic acid visualization

• Design and synthesis of non-toxic and economic magnetic nanoparticle colorant dye for nucleic acid visualization. • Development dual-functional nanoparticle have strong magnetic properties and intense fluorescent light. • Evaluation of particle adsorption loading efficiency and their release of nucleic acid. • The magnetic dye can be easy recovered and controlled their movement by applying external magnetic. Up to date most traditional fluorescent dyes that serve to detect nucleic acids in a selective manner face growing environmental and economic challenges due to their high toxicity, expensiveness, the long staining times required and the low sensitivities. Further attention went to replace the current widely used ethidium bromide (EB) by more safe and stable dyes but still some of the above drawbacks persist. In this work an innovative fluorescent dye has been designed and synthesized via impregnating perylene diimide into the functionalized surface of magnetic core–shell silica nanoparticles. One of the free hydroxyl groups on the perylene diimide enables the colored magnetic nanoparticles to easily disperse in water and their movement can be controlled with magnetism which allow the separation after their used. These particles are of low toxicity, environmentally friendly and have high sensitivity. Fluorescent properties and molecular interaction were studied. The designed particles show high DNA binding capacity which makes the developed particle promising for DNA extraction, delivery and fluorescent labeling. Theoretical studies confirm that the dye is placed between two DNA base pair similar with pervious observation with EB and the distance was less than 6 Å which is much less than the distance of EB dye interaction (15 Å) as reported before [1] .

Dual functional amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles for the monitoring and inhibition of insulin amyloid fibrillation based on carbohydrate-protein interactions.

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.

Evaluating the biocompatibility and biological performance of FePt-decorated nano-epoxy nanoparticles in mesenchymal stem cells.

Nanoparticles have wide potential applications in biolabeling, bioimaging, and cell tracking. Development of dual functional nanoparticles increases the versatility. We combined the fluorescent property of nano-epoxy (N-Epo) and the magnetic characteristic of FePt to fabricate the FePt-decorated N-Epo (N-Epo-FePt). The size in diameter of N-Epo-FePt (177.38 ± 39.25 nm) was bigger than N-Epo (2.28 ± 1.01 nm), both could be absorbed into mesenchymal stem cells (MSCs) via clathrin-mediated endocytosis and have multiple fluorescent properties (blue, green, and red). N-Epo-FePt prevented N-Epo-induced platelet activation, CD68+-macrophage differentiation in blood, and intracellular ROS generation in MSCs. The induction of apoptosis and the inhibitory effects of N-Epo-FePt on cell migration, MMP-9 activity, and secretion of SDF-1α were less than that of N-Epo in MSCs. N-Epo-FePt was more biocompatible without altering biological performance than N-Epo in MSCs. These results suggest that N-Epo-FePt nanoparticle can be used for fluorescence labeling of MSCs and is potential to apply to bioimaging and cell tracking of MSCs in vivo by magnetic resonance imaging or computed tomography.

Hybrid nanoparticles based on ortho ester-modified pluronic L61 and chitosan for efficient doxorubicin delivery

Tumor intrinsic or acquired multidrug resistance (MDR) is still one of the major obstacles to the success of nanomedicine. To address this, the pH-sensitive nanoparticles (L61-OE-CS) with MDR-reversal ability were prepared by the crosslinking between acid-labile ortho-ester-modified pluronic (L61-OE) and chitosan (CS) for efficient doxorubicin (DOX) delivery. The size and micromorphology of the prepared nanoparticles were observed by dynamic light scanning and scanning electron microscopy and the nanoparticles displayed a uniform spherical shape with a diameter around 200 nm. The pH-triggered morphology change of the nanoparticles was also observed by scanning electron microscope. Drug release profiles under different pH values showed that DOX release amount within 72 h reached 16% (pH 7.4) and 76.5% (pH 5.0), respectively. In vitro cellular uptake and MTT assay demonstrated that the ortho ester and pluronic-based nanoparticles had higher cytotoxicity than non-sensitive nanoparticles. In vivo antitumor experiments also proved the superiority of the dual-functional nanoparticles, and the tumor growth inhibition rate (TGI) on day 14 was higher than 80%. Therefore, L61-OE-CS nanoparticles have great potential to be used as drug carriers in anticancer therapy.

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment.

PurposeWith the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men’s health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment.MethodsBy a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation.ResultsWith a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa.ConclusionThe dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis.

AimIridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats.Materials and MethodsWe prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model.ResultsSEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2.ConclusionWe confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.

Preparation and Preliminary Evaluation of Dual-functional Nanoparticles for MRI and siRNA Delivery.

In order to improve the transfection efficiency of gene vectors and monitor the effect of gene therapy, this study prepared a drug delivery vector with dual functions. The thiourea reaction was used to synthesize polyethyleneimine (PEI, MW: 1.8 kDa) with superparamagnetic iron oxide nanoparticles (SPION) (PEI1800-SPION), and the lipid polycationic gene vector PEI1800-SPION loaded cationic liposome (LP-PEI1800-SPION) was further prepared by ethanol injection method. Agarose gel electrophoresis experiment, cytotoxicity experiment, and In-vitro gene silencing experiment were used to evaluate the vector and screen the optimal prescription of LP-PEI1800-SPION/siRNA. When the weight ratio of LP-PEI1800-SPION to siRNA is 20, the transfection efficiency of the nanoparticles was the highest, and the silencing efficiency of the target protein was the largest. The cytotoxicity of LP-PEI1800-SPION was low; when the concentration was in the range of 1-50 μg/mL, the survival rate of the four types of cells was above 80%. Prussian blue staining experiments and In-vitro MRI imaging experiments showed that cells had significant uptake and imaging capabilities for LP-PEI1800-SPION. In conclusion, the visualized polycationic lipid siRNA delivery vehicle (LP-PEI1800-SPION) was successfully prepared in this experiment, which provides a research basis for further theranostics of liver cancer.

Dual functional nanoparticles efficiently across the blood–brain barrier to combat glioblastoma via simultaneously inhibit the PI3K pathway and NKG2A axis

The blood–brain barrier (BBB) and complex tumour immunosuppressive micro-environment posed austere challenges for combatting brain tumours such as the glioblastoma. In this study, we have developed a novel dual functional dendrimer drug delivery system (DDS) by the PAMAM and loaded with siLSINCT5 (NP- siRNA) for efficiently across the BBB to inhibit glioblastoma. To achieve the goal of BBB crossing, on the surface of NP-siRNA was decorated with the cell penetrating peptides tLyp-1 (tLypNP-siRNA). Moreover, to overcome the immunosuppressive microenvironment within the glioblastoma (GBM) tissues, a checkpoint inhibitor named as anti-NKG2A monoclonal antibody (aNKG2A), which was able of promoting anti-tumour immunity by unleashing both T and NK Cells, was further conjugated on the surface of siLSINCT5-loaded nanoparticles via the pH-sensitive linkage. Therefore, the developed dual functional and siLSINCT5-loaded dendrimer nanoparticles (tLyp/aNKNP-siRNA) was supposed to have the ability to efficiently cross the BBB and inhibit GBM by simultaneously inhibit the LSINCT5-activated signalling pathways and activate the anti-tumour immunity. The hypothesis was thoroughly confirmed by in vitro cellular and in vivo animal experiments, and provided a novel strategy for combating glioblastoma.

Mediating the Fate of Cancer Cell Uptake: Dual-Targeted Magnetic Nanovectors with Biotin and Folate Surface Ligands.

Recognition of folate and biotin surface receptors by dual-functionalized nanoparticles (NPs) is key for site-selective receptor-mediated transport of anticancer drugs to cancer cells. We present here dopamine-capped iron oxide nanoprobes (Fe3O4, 10 ± 2 nm) containing two surface-grafted biologically relevant ligands, namely, folic acid (FA) and biotin (BT). The covalent attachment of both FA and BT on Fe3O4 nanoparticles was achieved by following carbodiimide coupling and click-chemistry protocols. The dual-function Fe3O4 probes were delivered into E-G7 and human HeLa cancer cell lines and tested toward their cellular uptake by immunofluorescence and flow cytometry analysis. Owing to receptor-mediated endocytosis, enhanced accumulation of nanoprobes in cancer cells was successfully monitored by confocal laser microscopy. When compared to dual-function probes, single-functionalized nanoparticles possessing either FA or BT ligands showed significantly reduced uptake in the tested cell lines, underlining the superior interaction potential of dual-purpose probes. A time-dependent receptor-mediated endocytosis of FA-Fe3O4-BT nanovectors was demonstrated by flow cytometry analysis, whereas the unfunctionalized NPs did not show any specificity in terms of uptake. Besides their specific uptake, the surface-functionalized nanoparticles exhibited promising cytotoxicity profiles by demonstrating good viability of more than 95% with analogous cancer cell lines. Our results demonstrate that dual and/or multivariate conjugation of receptor-specific ligands on NPs is highly effective in molecular recognition of surface biomarkers that enhances their potential in anticancer treatment for pretargeting-radio strategies based on biotin/avidin interactions.

High payload nanoparticles composed of 7-ethyl-10-hydroxycamptothecin and chlorin e6 for synergistic chemo-photodynamic combination therapy

Combined chemo-photodynamic therapy strategy is regarded as a potential strategy for advanced cancer treatments. Herein, novel high payload 7-ethyl-10-hydroxycamptothecin (SN38)/chlorin e6 (Ce6) NPs based on the collaborative assembly of the pre-obtained SN38–Ce6 complex and biocompatible amphiphilic block polymer DSPE-PEG2000 were successfully constructed. The self-assembly mechanism of the NPs was corporately disclosed as static quenching resulted from complex formation between DSPE-PEG2000 and the pre-acquired SN38–Ce6 complex via fluorescence quenching experiment. The high payload SN38/Ce6 NPs exhibited uniform rod-like morphology with a hydrodynamic radius of about 200 nm, a zeta potential of around −25 mV, and excellent storage stability. The high payload NPs showed efficient singlet oxygen generation capacity both in tube and in murine mammary carcinoma (4T1) cells under laser irradiation. Moreover, the in vitro cytotoxicity and in vivo antitumor efficacy of the NPs (with laser) against 4T1 cell lines model were proved to be statistically significant compared to CPT-11 injection and single-drug NPs due to synergistic chemo-photodynamic therapy and high cellular uptake efficiency. Meanwhile, the systemic toxicity of the NPs was basically absent. Conclusively, the high payload dual-functional nanoparticles could be served as a promising strategy for cancer treatment in clinic.

The Impact of Covalent Functionalization on Single-Walled Carbon Nanotube Biosensor Fluorescence and Function

Single-walled carbon nanotubes (SWCNTs) are advantageous signal transduction elements for biological imaging and sensing due to their notable fluorescence in the near-infrared (NIR) region with minimal light absorbance by water or scattering by tissue (1). Recently, exciting developments in SWCNT surface chemistry have shown the retention and improvement of fluorescence intensity in SWCNTs after covalent surface functionalization (2). These chemistries provide chemical handles for specific attachment of molecules of interest to the SWCNT surface while keeping the intrinsic SWCNT NIR fluorescence intact for bioimaging and sensing applications. However, despite their unperturbed fluorescence, it is unclear whether functionalized SWCNTs maintain their ability for molecular sensing, which necessitates a modulation in SWCNT fluorescence provided by the molecular recognition of a noncovalently surface-adsorbed polymer. We compare the photophysical properties of functionalized SWCNTs to their pristine counterparts, and show SWCNT optical properties remain available for sensing applications, however with noted attenuation of fluorescence modulation between certain surface coating and analyte pairs. Molecular recognition provided by phospholipid SWCNT surface coatings maintain their ability to detect molecular analytes such as fibrinogen and insulin. Conversely, DNA oligonucleotide surface coatings under-perform for molecular recognition of dopamine compared to sensors constructed from pristine SWCNTs. We also discuss the use of covalent handles to tune the intrinsic properties of the SWCNT surface for use as biological tools. Lastly, we explore the application of covalently functionalized SWCNTs as dual-functional nanoparticles with both targeting and sensing capabilities. Our work establishes the potential advantages and drawbacks of covalent SWCNT functionalization, despite preservation of SWCNT fluorescence, and implications for applications in molecular sensing.(1) Bonis-O’Donnell, J. T. D.; Page, R. H.; Beyene, A. G.; Tindall, E. G.; McFarlane, I. R.; Landry, M. P. Dual Near-Infrared Two-Photon Microscopy for Deep-Tissue Dopamine Nanosensor Imaging. Adv. Funct. Mater. 2017, 27 (39), 1–10.(2) Setaro, A.; Adeli, M.; Glaeske, M.; Przyrembel, D.; Bisswanger, T.; Gordeev, G.; Maschietto, F.; Faghani, A.; Paulus, B.; Weinelt, M.; et al. Preserving π-Conjugation in Covalently Functionalized Carbon Nanotubes for Optoelectronic Applications. Nat. Commun. 2017, 8, 1–7.

Facile synthesis of polypyrrole-rhodamine B nanoparticles for self-monitored photothermal therapy of cancer cells.

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.