Nanostructure Mediated Piezoelectric Effect of Tetragonal BaTiO3 Coatings on Bone Mesenchymal Stem Cell Shape and Osteogenic Differentiation.

In recent years, porous titanium (Ti) scaffolds with BaTiO3 coatings have been designed to promote bone regeneration. However, the phase transitions of BaTiO3 have been understudied, and their coatings have yielded low effective piezoelectric coefficients (EPCs < 1 pm/V). In addition, piezoelectric nanomaterials bring many advantages in eliciting cell-specific responses. However, no study has attempted to design a nanostructured BaTiO3 coating with high EPCs. Herein, nanoparticulate tetragonal phase BaTiO3 coatings with cube-like nanoparticles but different effective piezoelectric coefficients were fabricated via anodization combining two hydrothermal processes. The effects of nanostructure-mediated piezoelectricity on the spreading, proliferation, and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMSCs) were explored. We found that the nanostructured tetragonal BaTiO3 coatings exhibited good biocompatibility and an EPC-dependent inhibitory effect on hJBMSC proliferation. The nanostructured tetragonal BaTiO3 coatings of relatively smaller EPCs (<10 pm/V) exhibited hJBMSC elongation and reorientation, broad lamellipodia extension, strong intercellular connection and osteogenic differentiation enhancement. Overall, the improved hJBMSC characteristics make the nanostructured tetragonal BaTiO3 coatings promising for application on implant surfaces to promote osseointegration.

RGD-modified multifunctional nanoparticles encapsulating salvianolic acid A for targeted treatment of choroidal neovascularization.

BACKGROUND: The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4'-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA. RESULTS: We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by retinal pigment epithelium (RPE) cells which highly expressed ɑvß5 integrin receptors in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confirmed the biocompatibility of RGD-PEI/SAA. CONCLUSIONS: The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

Bivalent Peptide- and Chelator-Containing Bioconjugates as Toolbox Components for Personalized Nanomedicine.

While personalized therapy bears an enormous potential in cancer therapy, the development of flexible, tailorable delivery systems remains challenging. Here, we present a "tool-kit" of various avidin-based bioconjugates (BCs) for the preparation of personalized delivery systems. Corresponding BCs were synthesized using the self-assembly of avidin with various biotinylated ligands, such as one cationic glycodendrimer for dendriplex adsorption and two functional ligands for imaging (glycodendrimers with DOTA or NOTA units) or targeting (biotinylated PEG decorated with ligands). Substituting antibodies for targeting small molecules were coupled to biotin-PEG compounds for addressing the folate receptor (FR), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA). After successful characterization and proof of good storage and redispersion properties of BCs, cytotoxicity assays and first in vivo imaging studies with 99mTc-complexing bioconjugates provide evidence that these BCs and their avidin analogues can be used as tool-kit components in theranostic systems for personalized medicine.

Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery.

BACKGROUND: Glioma is the deadliest brain cancer in adults because the blood-brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. RESULTS: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. CONCLUSIONS: These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

99mTc-Labeled Polyethylenimine-Entrapped Gold Nanoparticles with pH-Responsive Charge Conversion Property for Enhanced Dual Mode SPECT/CT Imaging of Cancer Cells.

Development of tumor dual mode contrast agents is still a great challenge due to the relative low accumulation at tumor site, which result in the poor imaging efficiency. In this study, we constructed functional technetium-99m (99mTc) labeled polyethylenimine (PEI)-entrapped gold nanoparticles (Au PENs) with pH-responsive charge conversion property for enhanced single photon emission computed tomography (SPECT)/computed tomography (CT) dual mode imaging of cancer cells. PEI with amine functional groups (PEI.NH2) was successively modified with monomethyl ether and carboxyl functionalized polyethylene glycol (mPEG-COOH), maleimide and succinimidyl valerate functionalized PEG (MAL-PEG-SVA), diethylenetriaminepentaacetic dianhydride (DTPA), and fluorescein isothiocyanate (FI), and used to entrapped gold nanoparticles inside, followed by conjugation with the alkoxyphenyl acylsulfonamide (APAS) through the PEG maleimide, acetylation of the PEI leftover surface amines and 99mTc labeling. The created nanosystem with the mean Au core diameter of 3.3 nm and with a narrow size distribution displays an excellent colloidal stability and desired cytocompatibility in the investigated Au concentration range. Due to the fact that the attached APAS moieties are responsive to pH, the functionalized Au PENs with a neutral surface charge can switch to be positively charged under slightly acidic pH condition, which could improve the cellular uptake by cancer cells. With these properties, the developed functionalized Au PENs could achieve enhanced dual mode SPECT/CT imaging of cancer cells in vitro. The constructed PEI-based nanodevices may be adopted as an excellent dual mode contrast agent for SPECT/CT imaging of cancer cells of different types.

Chlorotoxin peptide-functionalized polyethylenimine-entrapped gold nanoparticles for glioma SPECT/CT imaging and radionuclide therapy.

BACKGROUND: Malignant glioma is the most common and deadliest brain cancer due to the obstacle from indistinct tumor margins for surgical excision and blood brain barrier (BBB) for chemotherapy. Here, we designed and prepared multifunctional polyethylenimine-entrapped gold nanoparticles (Au PENPs) for targeted SPECT/CT imaging and radionuclide therapy of glioma. RESULTS: Polyethylenimine was selected as a template for sequential modification with polyethylene glycol (PEG), glioma-specific peptide (chlorotoxin, CTX) and 3-(4-hydroxyphenyl)propionic acid-OSu (HPAO), and were then used to entrap gold nanoparticles (Au NPs). After 131I radiolabeling via HPAO, the 131I-labeded CTX-functionalized Au PENPs as a multifunctional glioma-targeting nanoprobe were generated. Before 131I radiolabeling, the CTX-functionalized Au PENPs exhibited a uniform size distribution, favorable X-ray attenuation property, desired water solubility, and cytocompatibility in the given Au concentration range. The 131I-labeled CTX-functionalized Au PENPs showed high radiochemical purity and stability, and could be used as a nanoprobe for the targeted SPECT/CT imaging and radionuclide therapy of glioma cells in vitro and in vivo in a subcutaneous tumor model. Owing to the unique biological properties of CTX, the developed nanoprobe was able to cross the BBB and specifically target glioma cells in a rat intracranial glioma model. CONCLUSIONS: Our results indicated that the formed nanosystem had the significant potential to be applied for glioma targeted diagnosis and therapy.

Nanorod diameter modulated osteogenic activity of hierarchical micropore/nanorod-patterned coatings via a Wnt/ß-catenin pathway.

Hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca9Sr1(PO4)6(OH)2, Sr1-HA) structures (MNRs) with different nanorod diameters of about 30, 70 and 150 nm were coated on titanium, to investigate the effect of nanorod diameter on osteogenesis and the involved mechanism. Compared to micropore/nanogranule-patterned Sr1-HA coating (MNG), MNRs gave rise to dramatically enhanced in vitro mesenchymal stem cell functions including osteogenic differentiation in the absence of osteogenic supplements and in vivo osseointegration related to the nanorod diameter with about 70 nm displaying the best effects. MNRs activated the cellular Wnt/ß-catenin pathway by increasing the expression of Wnt3a and LRP6 and decreasing the expression of Wnt/ß-catenin pathway antagonists (sFRP1, sFRP2, Dkk1 and Dkk2). The exogenous Wnt3a significantly enhanced the ß-catenin signaling activation and cell differentiation on MNG, and the exogenous Dkk1 attenuated the enhancing effect of MNRs on them. The data demonstrate that MNRs favor osseointegration via a Wnt/ß-catenin pathway.

The osteogenic capacity of biomimetic hierarchical micropore/nanorod-patterned Sr-HA coatings with different interrod spacings.

Advanced titanium based bone implant with fast established, rigid and stable osseointegration is stringently needed in clinic. Here the hierarchical micropore/nanorod-patterned strontium doped hydroxyapatite (Ca9Sr1(PO4)6(OH)2, Sr1-HA) coatings (MNRs) with different interrod spacings varying from about 300 to 33nm were developed. MNRs showed dramatically differential biological performance closely related to the interrod spacing. Compared to micropore/nanogranule-patterned Sr1-HA coating (MNG), MNRs with an interrod spacing of larger than 137nm resulted in inhibited in vitro mesenchymal stem cell functions and in vivo osseointegration, while those of smaller than 96nm gave rise to dramatically enhanced the biological effect, especially those of mean 67nm displayed the best effect. The differential biological effect of MNRs was related to their modulation on the focal adhesion mediated mechanotransduction. These results suggest that MNRs with a mean interrod spacing of 67nm may give rise to an advanced implant of improved clinical performance.

Treatment of Advanced Gingival Recession Secondary to Surgical Failure with Large Size Deepithelized Gingival Graft Associated with a Modified Tunnel Flap.

Objective: To describe the use of a large size deepithelized gingival graft (DGG) associated with full-split tunnel technique in a clinical case of advanced gingival recession secondary to surgical failure (GRSF). Clinical Considerations. The presented case report helped to achieve satisfactory root coverage, ideal keratinized tissue gain, improvement in soft tissue quality and esthetics, scar deformity correction, and vestibular depth deepening with a one-step procedure of large size DGG associated with full-split tunnel technique for a condition of deep gingival recessions of 7-11 mm caused by a failed bone implantation surgery. Conclusions: The large size DGG associated with full-split tunnel technique provided a versatile one-step procedure to obtain ideal results for advanced GRSF. Clinical Significance. GRSF that is generally associated with inadequate keratinized tissue and scar formation could be rather difficult to deal with. The large size DGG associated with full-split tunnel technique, as a one-step procedure, provided a predictable and practical treatment modality.

Near-infrared light-activated ROS generation using semiconducting polymer nanocatalysts for photodynamic-chemodynamic therapy.

Chemodynamic therapy (CDT) is an emerging treatment strategy for cancer, but the low therapeutic efficacy and potential side effects still limit its applications. In this study, we report a semiconducting polymer nanocatalyst (PGFe) that can generate reactive oxygen species (ROS) only upon near-infrared (NIR) light-activation for photodynamic therapy (PDT)-synergized CDT. Such PGFe consists of a semiconducting polymer as a photosensitizer, iron oxide (Fe3O4) nanoparticles as CDT agents, and glucose oxidase (GOx), all of which are loaded into a singlet oxygen (1O2)-responsive nanocarrier. Under NIR laser irradiation, PGFe produces 1O2 through a photosensitizer-mediated PDT effect, and the produced 1O2 destroys the 1O2-responsive nanocarriers, leading to controlled releases of Fe3O4 nanoparticles and GOx. In a tumor microenvironment, GOx catalyzes glucose degradation to form hydrogen peroxide (H2O2), and thus the CDT effect of Fe3O4 nanoparticles is greatly improved. As such, an amplified ROS level in tumor cells is obtained by PGFe to induce cell death. PGFe can be utilized to treat subcutaneous 4T1 tumors, observably inhibiting the tumor growth and suppressing lung and liver metastasis. This study thus provides a NIR light-activated ROS generation strategy for precise and effective treatments of tumors.

Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing.

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes (HDs) with integrin α6ß4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6ß4, which can promote adhesion, migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules, including integrin α6ß4, LN332 and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.

131I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors.

INTRODUCTION: Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge. METHODS: In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems. RESULTS: The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sustainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo. DISCUSSION: The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.

Charge-conversional polyethylenimine-entrapped gold nanoparticles with 131I-labeling for enhanced dual mode SPECT/CT imaging and radiotherapy of tumors.

Novel theranostic nanosystems demonstrate great potential to achieve timely diagnosis and effective therapy at the same time. However, due to the relatively low accumulation of theranostic nanosystems at the tumor site, the theranostic efficiency is limited. In this study, a novel theranostic nanosystem with a pH-responsive charge conversion property was constructed to improve the cellular uptake towards cancer cells for enhanced single photon emission computed tomography (SPECT)/computed tomography (CT) dual mode imaging and radiotherapy of tumors. In detail, polyethylenimine (PEI) was utilized as a nanoplatform to link with polyethylene glycol (PEG) monomethyl ether with one end of N-hydroxylsuccinimide (mPEG-NHS), PEG with ends of maleimide and succinimidyl valerate (MAL-PEG-SVA), alkoxyphenyl acylsulfonamide (APAS), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate (FI), successively. The formed functionalized PEI was then utilized to entrap gold nanoparticles, acetylate the remaining amines of PEI and label with radioactive iodine-131 (131I) to build theranostic nanosystems. The result demonstrated that the theranostic nanosystem has a 3.8 nm Au core and showed excellent colloidal stability. On account of the charge conversion property of APAS, the APAS linked PEI entrapped gold nanoparticles could switch from neutral to positive in a slightly acidic microenvironment, which induced improved cellular uptake. Above all, after 131I labeling, the generated theranostic nanosystem could achieve enhanced SPECT/CT dual mode imaging and radiotherapy of cancer cells in vitro and a xenograft tumor model in vivo. The constructed APAS-linked PEI nanosystem has great potential to be used as a model for SPECT/CT imaging and radiotherapy of various types of cancer.

Low-magnitude mechanical vibration may be applied clinically to promote dental implant osseointegration.

Dental implants have been widely used clinically, but there still remain great challenges for a stronger bone-implant bonding and a shorter rehabilitation time. Osseointegration of dental implant is crucial for their long term clinical success. Recently, there are abundant evidences showing that low mechanical stimuli can strengthen bones, inhibit osteopenia and enhance bone healing. It has been showed that low-amplitude mechanical stimuli have favorable influence on osteoblasts and their precursors. Preliminary studies indicated that low-magnitude mechanical stimuli may assist in implant osseointegration. So collectively we hypothesize that low-magnitude mechanical vibration may be applied clinically to strengthen and accelerate osseointegration of dental implants.

Antibacterial, angiogenic, and osteogenic activities of Ca, P, Co, F, and Sr compound doped titania coatings with different Sr content.

Titanium implants are often combined with microporous titania coatings simultaneously doped with various elements to enhance their antibacterial, angiogenic and osteogenic activities. To evaluate how Sr doping levels affect properties of titania coatings simultaneously doped with Ca, P, Co and F (TiCPCF coatings), we prepared coatings with Sr contents equal to 6, 11 and 18 wt% (TiCPCF-S6, TiCPCF-S11 and TiCPCF-S18, respectively) using micro-arc oxidation of titanium. Sr presence in TiCPCF coatings did not affect their phase compositions, microstructure, surface wettability, roughness, and adhesion to titanium. Antibacterial, angio- and osteo-genic activities of all the coatings were evaluated. Sr incorporation improved mesenchymal stem cell proliferation, osteogenic differentiation and implant osseointegration. TiCPCF-S11 showed the most optimum Sr content judging by its enhanced osteogenic activity. While Sr incorporation did not weaken angiogenic and antibacterial abilities of TiCPCF. Thus TiCPCF-S11 coating is a very strong candidate to be used as a next-generation bone implant material.

99mTc-Labeled LyP-1 for SPECT Imaging of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC), the most aggressive breast cancer type, is associated with high mortality and recurrence rates. An active-targeted strategy based on homing peptides is an effective approach to diagnose and treat cancer as it can deliver imaging agents or therapeutic drugs into desired tissues and accumulate less into off-target tissues. As a homing peptide, LyP-1 has shown properties of targeting, internalization, and proapoptosis to TNBC. In the study, we designed a Technetium-99m- (99mTc-) labeled LyP-1 and investigated its feasibility for targeted single-positron emission computed tomography (SPECT) imaging of TNBC. The results showed that the LyP-1 peptide had acceptable biocompatibility in the studied concentration range and could specifically bind to TNBC cells in vitro. 99mTc-labeled LyP-1 showed high radiochemical purity and stability and could be used as a probe for targeted SPECT imaging of TNBC cells in vitro and in a TNBC tumor-bearing mouse model. Our findings indicate that this active-targeted strategy has great potential to be developed into a new imaging tool for TNBC diagnosis.

131 I-Labeled Multifunctional Polyphosphazene Nanospheres for SPECT Imaging-Guided Radiotherapy of Tumors.

Design of theranostic nanoplatforms represents a major topic for current nanomedicine. Here, the preparation of multifunctional poly(cyclotriphosphazene-co-polyethylenimine) nanospheres (PNSs) labeled with radionuclide 131 I for single photon emission computed tomography (SPECT) imaging-guided radiotherapy of tumors is reported. In this work, PNSs are prepared using hexachlorocyclotriphosphazene as a crosslinker to crosslink branched polyethylenimine (PEI) via a nucleophilic substitution reaction, modified with 3-(4'-hydroxyphenyl) propionic acid-OSu (HPAO) for 131 I labeling, and reacted with 1,3-propane sulfonate (1,3-PS) to render the particles with antifouling property, followed by acetylation of the remaining surface amines and labeling with 131 I. The acquired PNS.NHAc-HPAO(131 I)-PS particles are well characterized. It is shown that the multifunctional PNSs with an average size of 184 ± 29.3 nm exhibit favorable antifouling properties, high 131 I labeling efficiency (76.05 ± 3.75%), and excellent radiostability and colloidal stability. With these properties owned, the developed PNS.NHAc-HPAO(131 I)-PS spheres enable much more efficient SPECT imaging and radiotherapy of a xenografted tumor model in vivo than the PEI counterpart material (PEI.NHAc-HPAO(131 I)-PS). The developed PNSs may be used as a versatile platform for further development of different forms of nanomedicine for various biomedical applications.

131I-labeled polyethylenimine-entrapped gold nanoparticles for targeted tumor SPECT/CT imaging and radionuclide therapy.

Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy. Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I). Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo. Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.

Titanium implant functionalized with antimiR-138 delivered cell sheet for enhanced peri-implant bone formation and vascularization.

Patients with compromised bone conditions still suffer the problem of deficient osseointegration during dental implant treatment. Developing mesenchymal stem cell (MSC) sheet functionalized titanium implant with proper inductive cue to promote osteogenesis and angiogenesis coupling shall be a good solution. In the present study, the antimiR-138 delivered MSC sheet is used to functionalize the Ti implant. The cell sheet can well integrate with the Ti implant to form the MSC sheet-implant complex (MSIC). The antimiR-138 delivered MSIC shows greatly improved osteogenesis and angiogenesis coupling both in vitro and in vivo. In vitro, the antimiR-138 delivered MSIC significantly promotes the expression of endogenous osteogenesis and angiogenesis related genes and proteins, alkaline phosphatase activity, extracellular matrix mineralization and collagen secretion compared to the antimiR-control and the nothing delivered control. The in vivo ectopic implantation assay uncovers the robust vascularized bone formation of the antimiR-138 delivered MSIC. The antimiR-138 delivered MSIC with promoted osteogenesis and angiogenesis coupling is anticipated to lead to rigid osseointegration in the compromised bone conditions.

99mTc-labelled multifunctional polyethylenimine-entrapped gold nanoparticles for dual mode SPECT and CT imaging.

In this study, we report the synthesis, characterization and utilization of 99mTc-labelled polyethylenimine-entrapped gold nanoparticles (99mTc-Au-PENPs) for dual mode single-photon emission computed tomography/computed tomography (SPECT/CT) imaging applications. Polyethylenimine (PEI) was selected as a platform to conjugate with diethylene triamine pentacetate acid (DTPA) and polyethylene glycol monomethyl ether to synthesize Au PENPs, followed by acetylation or hydroxylation modification of the remaining PEI surface amine groups and radiolabelling of 99mTc. The generated multifunctional 99mTc-Au-PENPs with different surface groups (acetyl or hydroxyl) were characterized via different methods. The Au PENPs before 99mTc labelling are colloidally stable, haemocompatibility and noncytotoxic at an Au concentration up to 100 µM. The 99mTc-labelled Au PENPs exhibit high radiochemical purity, good stability and SPECT/CT imaging performance of different organs and lymph node. The designed strategy to use the radionuclide labelling technique and PEI-facilitated versatile nanoplatform may be extended to develop various novel nanoprobes for precision imaging applications.