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Addressing adipose niche senescence is crucial for preventing obesity‐related aging. Telomerase reverse transcriptase (TERT) is a promising target for gene therapy, but traditional methods lack precision and safety. A novel mitochondrion‐located TERT (mito‐TERT) activating approach is presented by injectable gene/short‐fiber complexes (gene/fiber‐plexes) to safely reverse adipose niche senescence from mitochondrial enhancement. The gene/fiber‐plexes are prepared from polydopamine‐coated short‐fibers to adsorb cationic dendrimers (PAMAM G3, PG3) carrying TERT plasmids and Coenzyme Q10 (CoQ10), termed PG3‐TERT@CoQ10. Upon intraperitoneal injection, the gene/fiber‐plexes adhere to the peritoneum and release PG3‐TERT@CoQ10, precisely targeting the adipose niche. Transient active oxygen scavenging by CoQ10 activates TERT transfection and endogenous mitochondrion translocation sequentially, enhancing mitochondrial function. In vitro and in vivo studies shows that gene/fiber‐plexes effectively targeted visceral adipose tissue, increased mito‐TERT levels and restored mitochondrial function. In an obese mouse model, they restored adipose tissue homeostasis and metabolic stability. RNA sequencing indicated reduced senescence‐related genes and restored cell cycle. This mito‐TERT activation strategy shows great promise for treating premature aging and metabolic diseases linked to adipose tissue senescence. [ABSTRACT FROM AUTHOR]

Xiangbo Zeng,1,2,* Dingrui Nie,1,3,* Zhen Liu,2 Xueting Peng,1 Xianfeng Wang,1 Kangjie Qiu,1 Shuxin Zhong,1 Ziwei Liao,4 Xianfeng Zha,1,5 Yangqiu Li,1,2 Chengwu Zeng1 1Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 4Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510180, People’s Republic of China; 5Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yangqiu Li; Chengwu Zeng, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of China, Email yangqiuli@hotmail.com; bio-zcw@163.comIntroduction: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease with limited targeted therapy options. Overexpression of B-cell lymphoma/leukemia 11B is frequently observed in T-ALL and contributes to leukemogenesis. Knockdown of BCL11B inhibits T-ALL cell proliferation and induces apoptosis, making it a potential therapeutic target. However, the clinical application of siRNA therapies is hindered by challenges such as poor delivery efficiency and limited clinical outcomes.Methods: We developed a targeted delivery system for BCL11B siRNA (siBCL11B) using generation 5 polyamidoamine (G5-PAMAM) dendrimers conjugated with the sgc8 aptamer, which specifically binds to the T-ALL cell membrane protein PTK7. This nanoparticle, designated G5-sgc8-siBCL11B, was designed to selectively deliver siRNA to T-ALL cells. In vitro and in vivo experiments were conducted to evaluate its therapeutic efficacy and safety.Results: We demonstrate that sgc8-conjugated siBCL11B nanoparticles selectively and efficiently target BCL11B-overexpressing T-ALL cells, significantly inhibiting cell viability and promoting apoptosis while exhibiting minimal impact on the viability of normal T cells. In T-ALL mouse model studies, G5-sgc8-siBCL11B and G5-siBCL11B significantly inhibited the progression of T-ALL in vivo, extending the survival of mice compared to the control (CTR), G5, and G5-sgc8 groups. Although there was no significant difference in survival between the G5-sgc8-siBCL11B and G5-siBCL11B groups, a trend towards improved survival was observed (p = 0.0993).Conclusion: The G5-sgc8-siBCL11B nanoparticle system demonstrated efficient delivery and significant therapeutic efficacy, highlighting its potential as a promising novel approach for the treatment of T-ALL.Keywords: BCL11B, T-ALL, aptamer, sgc8, siBCL11B, PAMAM

Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Magnetic particles with active groups on their surfaces can be applied to wastewater purification to remove harmful ions, but the insufficient number of active groups on their surfaces tends to limit their removal rate of ions. Herein, we grafted different generations of dendritic macromolecular polyamidoamine (PAMAM) onto the magnetic chitosan microspheres (MCS) using ethylenediamine tetraacetic acid (EDTA) as core (MCEPs) for the removal of Cu (II). Firstly, 7 μm-sized MCS with good dispersibility was prepared by adjusting conditions such as glacial acetic acid content, emulsifier content and raw material ratio. Secondly, the effect of MCEPs generation, pH and contact time on the adsorption capacity were investigated. The adsorption experiments showed that the MCEPs had a high adsorption capacity, when the adsorbent was the second generation of MCEP (MCEP G2.0), the maximum adsorption capacity can up to 702.9 mg/g and the adsorption process can be completed in 60 min. Moreover, among various isotherms models, MCEP G2.0 was well-fitted by Langmuir adsorption isotherm. Also, adsorption kinetic studies proved that the adsorption mechanism of MCEP G2.0 adsorbent followed the pseudo-second-order kinetic model, demonstrating that the process was chemisorption. The adsorbent has renewability as well, after five adsorption cycles, its adsorption efficiency was still higher than 80%. Therefore, the adsorbent showed a superior adsorption capacity and renewability to remove Cu (II). [ABSTRACT FROM AUTHOR]

Abstract Hydatidosis causes a serious health hazard to humans and animals leading to significant economic and veterinary and public health concern worldwide. The present study aimed to evaluate the in vitro and ex vivo protoscolicidal effects of synthesized poly(amidoamine), PAMAM, nanoemulsion. In this study, PAMAM was characterized through dynamic light scattering technique to investigate the particle size and zeta potential of nanoemulsified polymer. For the in vitro and ex vivo assays, we used eosin dye exclusion test and scanning electron microscope (SEM) to evaluate the effects of the prepared and characterized PAMAM nanoemulsion against protoscoleces from Echinococcus granulosus sensu lato G6 (GenBank: OQ443068.1) isolated from livers of naturally infected camels. Various concentrations (0.5, 1, 1.5 and 2 mg/mL) of PAMAM nanoemulsion at different exposure times (5, 10, 20 and 30 min) were tested against protoscolices. Our findings showed that PAMAM nanoemulsion had considerable concentration- and time-dependent protoscolicidal effect at both in vitro and ex vivo experiments. Regarding in vitro assay, PAMAM nanoemulsion had a potent protoscolicidal effect when compared with the control group with a highest protoscolicidal activity observed at the concentration of 2 mg/mL at all exposure times, such that 100% of protoscolices were killed after 20 min of exposure. Also, the mortality of protoscolices was 100% after 30 min of exposure to 1 and 1.5 mg/mL of PAMAM nanoemulsion, in vitro. Concerning ex vivo assay PAMAM nanoemulsion recorded the highest mortality rates at the concentration of 2 mg/mL (55, 99.4 and 100% at 10, 20, 30 min, respectively). Ultrastructure examination of examined protoscolices after 20 min of exposure to PAMAM nanoemulsion showed a complete loss of rostellar hooks, disruption of suckers with disorganization of hooks with partial or complete loss of them, and damage of protoscolices tegument with loss of their integrity in the form of holes and contraction of the soma region were observed in 1.5 and 2 mg/mL of PAMAM, in vitro and ex vivo, showing more damage in the in vitro conditions. It can be concluded that PAMAM nanoemulsion is a promising protoscolicidal agent offering a high protoscolicidal effect at a short exposure time. Further in vivo studies and preclinical animal trials are required to evaluate its efficacy and clinical applications against hydatid cysts.

This study was aimed to develop and evaluate the TMZ-PAMAM-siRNA [temozolomide-polyamidoamine dendimer-siRNA] dendriplexes for the effective treatment of glioblastoma multiforme (GBM). In the present study, TMZ-PAMAM-siRNA dendriplexes were designed with optimized N/P ratio for the effective management of GBM. Complexation was performed using mixing followed by incubation in nuclease free water. The particle size and zeta potential of the developed dendriplexes were found to be 121.54 ± 8.21 nm and 12.56 ± 0.91 mV, respectively. Drug loading and entrapment efficiency of TMZ-PAMAM-siRNA were observed to be 38.41 ± 3.47% and 56.24 ± 3.94%, respectively. TMZ-PAMAM-siRNA exhibited minimal toxicity towards RBCs with controlled drug release behaviour in the acidic medium. TMZ-PAMAM-siRNA complex was reversible in nature and was able to release siRNA from dendriplexes. IC50 values were reduced in case of TMZ-PAMAM (p < 0.0001) and TMZ-PAMAM-siRNA (p < 0.0001). TMZ-PAMAM resulted in the IC50 values to be 419.47 ± 17.24 and 252.21 ± 15.64 μM after 24 and 48 h of treatment, respectively. The developed dendriplexes showed significantly higher cytotoxic effect with IC50 values of 295.30 ± 21.56 μM after 24 h of treatment against LN229 cells. However, maximum cytotoxic effect was observed after 48 h of treatment and calculated IC50 value was 197.52 ± 18.12 μM. The results of cellular internalization supported the results obtained through MTT assay. The siRNA complexed PAMAM dendrimers have shown excellent potential in delivering drugs to the targeted cells. Such dendriplex-based approach can result into promising output if explored further. [ABSTRACT FROM AUTHOR]

Hydatidosis causes a serious health hazard to humans and animals leading to significant economic and veterinary and public health concern worldwide. The present study aimed to evaluate the in vitro and ex vivo protoscolicidal effects of synthesized poly(amidoamine), PAMAM, nanoemulsion. In this study, PAMAM was characterized through dynamic light scattering technique to investigate the particle size and zeta potential of nanoemulsified polymer. For the in vitro and ex vivo assays, we used eosin dye exclusion test and scanning electron microscope (SEM) to evaluate the effects of the prepared and characterized PAMAM nanoemulsion against protoscoleces from Echinococcus granulosus sensu lato G6 (GenBank: OQ443068.1) isolated from livers of naturally infected camels. Various concentrations (0.5, 1, 1.5 and 2 mg/mL) of PAMAM nanoemulsion at different exposure times (5, 10, 20 and 30 min) were tested against protoscolices. Our findings showed that PAMAM nanoemulsion had considerable concentration- and time-dependent protoscolicidal effect at both in vitro and ex vivo experiments. Regarding in vitro assay, PAMAM nanoemulsion had a potent protoscolicidal effect when compared with the control group with a highest protoscolicidal activity observed at the concentration of 2 mg/mL at all exposure times, such that 100% of protoscolices were killed after 20 min of exposure. Also, the mortality of protoscolices was 100% after 30 min of exposure to 1 and 1.5 mg/mL of PAMAM nanoemulsion, in vitro. Concerning ex vivo assay PAMAM nanoemulsion recorded the highest mortality rates at the concentration of 2 mg/mL (55, 99.4 and 100% at 10, 20, 30 min, respectively). Ultrastructure examination of examined protoscolices after 20 min of exposure to PAMAM nanoemulsion showed a complete loss of rostellar hooks, disruption of suckers with disorganization of hooks with partial or complete loss of them, and damage of protoscolices tegument with loss of their integrity in the form of holes and contraction of the soma region were observed in 1.5 and 2 mg/mL of PAMAM, in vitro and ex vivo, showing more damage in the in vitro conditions. It can be concluded that PAMAM nanoemulsion is a promising protoscolicidal agent offering a high protoscolicidal effect at a short exposure time. Further in vivo studies and preclinical animal trials are required to evaluate its efficacy and clinical applications against hydatid cysts. [ABSTRACT FROM AUTHOR]

Composites of rhenium (ReNP) and rhenium–copper nanoparticles (ReCuNP) were studied as catalysts for the decomposition of the oxidizer ammonium perchlorate (AP) for composite solid propellants. Both composites were prepared by reducing ammonium perrhenate (NH4ReO4) and copper chloride (CuCl2) in the presence of polyamidoamine (PAMAM) dendrimers. The PAMAM-based nanostructures were characterized by transmission electron microscopy (TEM), high resolution TEM, and X-ray photoelectron spectroscopy. ReNP@PAMAM samples showed rhenium clusters and partially oxidized spherical nanoparticles of approx. 1 nm in diameter, while ReCuNP@PAMAM comprised nanoparticles of 6 nm in average size with different shapes and high-size dispersion. The computational description demonstrated the higher stability of the interaction between copper and PAMAM than perrhenate anion due to the charge transfer from the dendrimer to the cation. The materials were evaluated for the catalytic decomposition of AP by calorimetry. The catalytic performance of ReCuNP@PAMAM was superior to that of ReNP@PAMAM, lowering the decomposition of AP at high temperatures. However, the latter composite increased the energy release drastically due to the exothermic oxidation of rhenium metal. [ABSTRACT FROM AUTHOR]

Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper. However, copper is also known to induce the proliferation of cancer cells. In view of these contradictory results, there is a need to find the most suitable copper chelators, among which Schiff-based derivatives offer a wide range of possibilities. Gathering several metal complexes in a single, larger entity may provide enhanced properties. Among the nanometric objects suitable for such purpose are dendrimers, precisely engineered hyperbranched macromolecules, which are outstanding candidates for improving therapy and diagnosis. In this review article, we present an overview of the use of a particular Schiff base, namely pyridine–imine, linked to the surface of dendrimers, suitable for complexing copper, and the use of such dendrimer complexes in biology, in particular against cancers. [ABSTRACT FROM AUTHOR]

This study details the effect of surface and bulk functionalization of poly(lactic acid) (PLA) with an amine‐terminated dendritic polymer, poly(amidoamine) (PAMAM), on the thermal and mechanical properties of PLA‐based formulations. Fourier‐transform infrared spectroscopy (FTIR) confirmed the presence of –NH2 groups derived from PAMAM, through emerging new peaks at around 1650 cm−1 associated with –NH bending vibration and separate double peak between 3705 and 3110 cm−1 associated with stretching vibration of –NH amide groups, in both surface and bulk functionalized PLA samples. Differential scanning calorimetry (DSC) measurements revealed a lowering of cold‐crystallization temperature (Tcc) for both surface and bulk functionalized PLA, suggesting that PAMAM served as a nucleating agent. According to thermogravimetric results (TGA), bulk treatment deteriorated the thermal stability of the polymer; while surface modification did not influence the decomposition pathway. Mechanical test results revealed that PAMAM greatly influenced the stiffens and ductility of the composites, with more pronounced changes for higher aminolysis rates. Therefore, the 3‐h PAMAM surface functionalization of PLA limits its affinity to solvents' content and enhances crystallization upon permissible deterioration in mechanical properties. Highlights: Development of aminolyzed‐PLA by surface and bulk modification with PAMAM dendritic polymer.PAMAM as a nucleating agent for PLA.Surface modification as the favorable condition to introduce NH2 groups to PLA. [ABSTRACT FROM AUTHOR]

Development of novel nano therapeutic material is of great interest among the researchers and with continuous advancement in nanotechnology, dendrimer a monodispersed unimicellar nanosize drug carrier with spacious globular 3D architecture in which the drug can be encapsulated is widely explored. This encapsulation of drug improves its pharmacokinetic and pharmacodynamics properties and more importantly enhances their bioavailability. A dendrimer based drug delivery system is a boon in targeted drug delivery. Its applications are not restricted to the pharmaceutical or medical field but also in other fields of science. The presence of various functional groups on the periphery has made their surface modifiable with therapeutic drugs, diagnostic agents, and targeting ligands. The vast surface area shows its capability to be used as a catalyst in chemical reactions too. And its biocompatibility makes its use much more effective and safer than other nano-carriers. This review tries to give a comprehensive description of this nano therapeutic, its properties, characteristics, method of synthesis, pharmacokinetics, toxicity, and recent applications in various fields, which can help the researchers for producing more promising outcomes of the dendrimers. [ABSTRACT FROM AUTHOR]

In this study, an attempt was made to synthesize a new sorbent based on the second generation of silica coated magnetic poly(amidoamine) (Fe3O4@SiO2@PAMAM) to improve the performance of magnetic solid phase extraction (MSPE) of some antifungal drugs including miconazole, clotrimazole and ticonazole in various real samples such as urine and human plasma. The extracted analytes were measured by high performance liquid chromatography equipped with ultraviolet detection (HPLC-UV). Field emissionscanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and Fourier transform-infrared spectroscopy (FT-IR) were used to study the morphology and structure of the prepared sorbent. The various factors such as: extraction time, sorbent amount, solvent desorption volume, desorption time, ionic strength and pH were studied and optimized. The method was validated according to ICH guidelines with respect to precision, accuracy, linearity, specificity, robustness, and limits of detection and quantification. Under the optimized condition, the linearity of the method was in the range of 1-500 µg L-1 (miconazole= 1-200 µg L-1, clotrimazole = 1-500 µg L-1 and ticonazole = 1-200 µg L-1). The obtained coefficient of determination (r²) were between 0.9871-0.9977. The limits of detection (LODs) were also calculated to be 0.14-0.18 µg L-1 (miconazole= 0.16 µg L-1, clotrimazole = 0.18 µg L-1 and ticonazole=0.14 µg L-1). The limits of quantification (LOQs) were also in the range of 0.46-0.60 µg L-1 for the selected analytes. The relative standard deviations (RSDs%), were obtained in the range of 4.6 to 5.9%. Moreover, the calculated enrichment factors were between 85 and 93. The proposed method was employed for the analysis of various real samples such as urine and plasma samples. The obtained recoveries (higher than 92%) indicated that the method was useful and applicable in complicated real samples. [ABSTRACT FROM AUTHOR]

In this study, an attempt was made to synthesize a new sorbent based on the second generation of silica coated magnetic poly(amidoamine) (Fe3O4@SiO2@PAMAM) to improve the performance of magnetic solid phase extraction (MSPE) of some antifungal drugs including miconazole, clotrimazole and ticonazole in various real samples such as urine and human plasma. The extracted analytes were measured by high performance liquid chromatography equipped with ultraviolet detection (HPLC-UV). Field emission-scanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and Fourier transform-infrared spectroscopy (FT-IR) were used to study the morphology and structure of the prepared sorbent. The various factors such as: extraction time, sorbent amount, solvent desorption volume, desorption time, ionic strength and pH were studied and optimized. The method is validated according to ICH guidelines with respect to precision, accuracy, linearity, specificity, robustness, and limits of detection and quantification. Under the optimized condition, the linearity of the method was in the range of 1–500 µg L-1 (miconazole= 1-200 µg L-1, clotrimazole = 1-500 µg L-1 and ticonazole = 1-200 µg L-1). The obtained correlation coefficients (r^2) were between 0.9871-0.9977. The limits of detection (LODs) were also calculated to be 0.14-0.18 µg L-1 (miconazole= 0.16 µg L-1, clotrimazole = 0.18 µg L-1 and ticonazole=0.14 µg L-1). The limits of quantification (LOQs) were also in the range of 0.46-0.60 µg L-1 for the selected analytes. The relative standard deviations (RSDs%), were obtained in the range of 4.6 to 5.9%. Moreover, the calculated enrichment factors were between 85 and 93. The proposed method was also employed for the analysis of various real samples such as urine and plasma samples. The obtained recoveries indicated that the method was useful and applicable in complicated real samples

Abstract Background Osteoporosis, among other bone diseases, has become a prevalent cause of decreased quality of life in older and postmenopausal women. Traditional anti-osteoporotic therapies, though widely prescribed, are limited by a lack of cell- or tissue-specific targeting ability and effectiveness without side effects. Gene therapy is rapidly replacing traditional therapeutics, primarily because of its specific targeting ability and efficiency. Among viral- and non-viral-based gene therapies, the latter is often preferred over the former due to lower cytotoxicity, immunogenicity, and ease of modification with different molecules to improve efficiency and extend gene expression. We designed and synthesized a multifunctional bone-targeting ribonucleic acid (RNA) delivery system based on polyamidoamine (PAMAM). PAMAM was modified with the serine-aspartate-serine-serine-aspartate (SDSSD) peptide to deliver antagomir 138-5p to osteoblasts (MC3T3-E1 cell line) in vitro and in vivo using the ovariectomized (OVX) mouse model. Results The results showed that this system was less cytotoxic than polyethylenimine (PEI) and could bind to RNA favorably while maintaining gene delivery ability in vitro. In vivo data showed that the distal tibia and femur of the mice in the PAMAM-SDSSD (PS) + RNA group had improved bone mineral density (BMD), bone mineral content (BMC), and bone volume compared to those in the PS + Negative Control (NC) or OVX groups. Moreover, the femurs of the PS + RNA group mice demonstrated a higher breaking point, stress, stiffness, and elasticity than those of the PS + NC or OVX mice, suggesting improved femur strength in the OVX mice treated with RNA delivered through SDSSD-modified PAMAM. Conclusion This study shows that SDSSD modification of PAMAM not only improves gene delivery capacity but also enhances the cell targeting efficiency of nanoparticles towards osteoblasts. The successful delivery of antagomir 138-5p to osteoblasts demonstrates cell-specificity and gene delivery to alleviate osteoporotic symptoms.

Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.

Dendrimers are a family of nano‐sized three‐dimensional polymers with unique dendritic branching structures and compact spherical geometries. In recent years, dendrimers have made a series of breakthroughs in the biomedical field. In this review, we introduce the synthesis principles, modification methods, and new materials designed based on dendrimers; discuss the importance of cytotoxicity of dendrimers for applications; and elaborate on their applications in the field of molecular assembly and cancer diagnosis and treatment. We speculate that in the near future, more new materials based on dendrimers will be applied in the biomedical field. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis, among other bone diseases, has become a prevalent cause of decreased quality of life in older and postmenopausal women. Traditional anti-osteoporotic therapies, though widely prescribed, are limited by a lack of cell- or tissue-specific targeting ability and effectiveness without side effects. Gene therapy is rapidly replacing traditional therapeutics, primarily because of its specific targeting ability and efficiency. Among viral- and non-viral-based gene therapies, the latter is often preferred over the former due to lower cytotoxicity, immunogenicity, and ease of modification with different molecules to improve efficiency and extend gene expression. We designed and synthesized a multifunctional bone-targeting ribonucleic acid (RNA) delivery system based on polyamidoamine (PAMAM). PAMAM was modified with the serine-aspartate-serine-serine-aspartate (SDSSD) peptide to deliver antagomir 138-5p to osteoblasts (MC3T3-E1 cell line) in vitro and in vivo using the ovariectomized (OVX) mouse model. Results: The results showed that this system was less cytotoxic than polyethylenimine (PEI) and could bind to RNA favorably while maintaining gene delivery ability in vitro. In vivo data showed that the distal tibia and femur of the mice in the PAMAM-SDSSD (PS) + RNA group had improved bone mineral density (BMD), bone mineral content (BMC), and bone volume compared to those in the PS + Negative Control (NC) or OVX groups. Moreover, the femurs of the PS + RNA group mice demonstrated a higher breaking point, stress, stiffness, and elasticity than those of the PS + NC or OVX mice, suggesting improved femur strength in the OVX mice treated with RNA delivered through SDSSD-modified PAMAM. Conclusion: This study shows that SDSSD modification of PAMAM not only improves gene delivery capacity but also enhances the cell targeting efficiency of nanoparticles towards osteoblasts. The successful delivery of antagomir 138-5p to osteoblasts demonstrates cell-specificity and gene delivery to alleviate osteoporotic symptoms. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface. In this study, we successfully conjugated an RRHRH oligopeptide to the surface of PAMAM generation 2 (PAMAM G2) to create RRHRH-PAMAM G2. This construction aims to condense plasmid DNA (pDNA) and facilitate its penetration into cell membranes, leading to its promising potential for gene therapy. RRHRH-PAMAM G2/pDNA complexes were smaller than 100 nm and positively charged. Nano-polyplexes can enter the cell and show a high transfection efficiency after 24 h of transfection. The RRHRH-PAMAM G2 was non-toxic to HeLa, NIH3T3, A549, and MDA-MB-231 cell lines. These results strongly suggest that RRHRH-PAMAM G2 holds promise as a gene carrier for gene therapy owing to its biocompatibility and ability to deliver genes to the cell. [ABSTRACT FROM AUTHOR]

Sensitive detection of ochratoxin A (OTA) is significant and essential because OTA may pose risks to human and animal health. Here, we developed an electrochemical aptasensor for OTA analysis using polyamidoamine (PAMAM) dendrimers as a signal amplifier. As a carrier, PAMAM has numerous primary amino groups that can be coupled with thiolated complementary strand DNA (cDNA), allowing it to recognize aptamers bound to the surface of horseradish peroxidase (HRP)-modified gold nanoparticles (AuNPs), thereby improving the sensitivity of the aptasensor. When monitoring the positive samples, OTA was captured by the aptamer fixed on the HRP-conjugated AuNP surface by specific recognition, after which the formed OTA-aptamer conjugates were detached from the electrode surface, ultimately decreasing the electrochemical signal monitored by differential pulse voltammetry. The novel aptasensor achieved a broad linear detection range from 5 to 105 ng L−1 with a low detection limit of 0.31 ng L−1. The proposed aptasensor was successfully applied for OTA analysis in red wine, with recovery rates ranging from 94.15 to 106%. Furthermore, the aptasensor also exhibited good specificity and storage stability. Therefore, the devised aptasensor represents a sensitive, practical and reliable tool for monitoring OTA in agricultural products, which can also be adapted to other mycotoxins. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polyamidoamine dendrimers (PAMAM) are nanoscale monodisperse compounds with a multifunctional terminal surface. Structural features of PAMAM, such as a nanosize of high homogeneity, highly developed terminal surface and cavities in the structure open up wide possibilities for their application. The most promising use of PAMAM is for biomedical purposes, in particular for the targeted drug delivery (for example, anticancer drugs). The interaction of PAMAM with target cells can be assessed using fluorescent imaging. This suggests the preliminary modification of PAMAM with various fluorescent molecules or the development of approaches to increase the intrinsic fluorescence of PAMAM. Materials and Methods: In this paper, we will consider a one-step modification of PAMAM based on the double cyclization reaction of PAMAM terminal groups and citric acid. Two approaches are chosen for modification: hydrothermal and boiling methods. The methods of optical spectroscopy and dynamic light scattering will be used as the main research tools. The methods used make it possible to determine the efficiency of fluorophore formation under given conditions. Results: In this work, we have proposed and implemented a one-step modification of PAMAM with a bright blue fluorophore (1,2,3,5-tetrahydro-5-oxo-imidazo[1,2-a] pyridine-7-carboxylic acid, IPCA), which is formed by a double cyclization reaction between citric acid and terminal ethylenediamine fragments of PAMAM. It has been shown that as a result of modification the hydrodynamic diameter of PAMAM does not change, the fluorescence intensity increases significantly (the quantum yield increases from < 1 to 28%), ζ-potential changes from 42 ± 5 to −24 ± 4 mV. Conclusion: Reaction of PAMAM and citric acid leads to the appearance of bright-blue fluorescence, which is significantly higher than the intrinsic fluorescence of PAMAM. A combination of bright fluorescence and a multifunctional terminal surface make it possible to further use the obtained structures for biovisualization.

Abstract Dendrimers are a family of nano‐sized three‐dimensional polymers with unique dendritic branching structures and compact spherical geometries. In recent years, dendrimers have made a series of breakthroughs in the biomedical field. In this review, we introduce the synthesis principles, modification methods, and new materials designed based on dendrimers; discuss the importance of cytotoxicity of dendrimers for applications; and elaborate on their applications in the field of molecular assembly and cancer diagnosis and treatment. We speculate that in the near future, more new materials based on dendrimers will be applied in the biomedical field.

Graph G has two sets of information: the vertices, V(G), and the edges, E(G). The definitions for the Connectivity, Geometric Arithmetic, Atomic Bond, and Sum Connectivity Indices of G: were deg(u), deg(v) are a degree of vertices. Dendrimers are synthetic, man-made molecules that are composed of monomers organized in a branching structure. in this article, we calculate Connectivity, Geometric Arithmetic, Atom Bond Connectivity, and Sum Connectivity Index for the PAMAM, POPAM, and HACN1J dendrimers.

A mixed-matrix nanofiltration membrane was fabricated by introducing a PAMAM dendrimer functionalized multiwall carbon nanotubes as a hydrophilic nanofiller and the membrane was prepared by phase inversion method. Fourier transform infrared spectra (FTIR), Transmission electron microscopy (TEM) and Field emission scanning electron microscope (FE-SEM) image analyses were used to identify the modified membranes and nanocomposite. The hydrophilicity and surface roughness of the prepared membrane was determined by Atomic force microscopy (AFM), Zeta potential, Thermogravimetric analysis (TGA) and Water contact angle (WCA), respectively. These results showed higher surface roughness and hydrophilicity of the modified membrane. The rejection performance of the membrane was measured by filtering Direct red 2 and Direct blue 1 solution (100 mg/L). The cellulose acetate (CA) membrane that was mixed with 1.0 wt% exhibited optimum performance above 90% rejection of both dyes with pore diameter of 0.73 nm and molecular weight cut off (MWCO) of 570 Da. Also, the antifouling properties of the prepared membrane were studied by filtration of bovine serum albumin (BSA) protein as a fouling agent. According to the data, compared to the bare CA membrane, the membrane containing nanofiller shows better antifouling. In addition, the membranes containing hydrophilic nanofiller showed better mechanical strength compared to the empty membrane. [ABSTRACT FROM AUTHOR]

In this study, a novel electrochemical aptamer sensor for detecting ochratoxin A (OTA) was constructed. First, a gold-copper alloy film was prepared via electrochemical deposition, and copper was selectively dissolved in constant potential mode for obtaining the nano-porous gold modified screen-printed carbon electrodes (NPG/SPCE). Then, 2-mercaptoethylamine was dropped on the NPG/SPCE surface and Au-S covalent bonds were formed for immobilizing the metal. Glutaraldehyde as cross-linking agent was added, which resulted in immobilization and attachment of PAMAM to the 2-mercaptoethylamine through the dehydration condensation reaction. During the preparation process, the nano-porous gold and PAMAM-modified layers were characterized by SEM, XRD, and IR spectroscopy, respectively. The characterization results showed that the nano-porous gold and PAMAM composite films were successfully modified. Finally, the OTA aptamer was cross-linked with PAMAM by glutaraldehyde to complete construction of the Apt/PAMAM/NPG/SPCE sensor. The electrochemical performance of this sensor was tested in ochratoxin A solutions with the DPV method. The results showed that the sensor's reproducibility, stability, and specificity were good. The spiked recoveries in red wine ranged from 99.65%∼101.6%, with a linear range of 0.5 ng/mL∼20 ng/mL and a minimum detection limit of 0.141 ng/mL. Thus, the novel biosensor may provide a promising tool for the trace detection of OTA. [ABSTRACT FROM AUTHOR]

The circadian clock controls behavior and physiology. Presently, there is clear evidence of a connection between this timing system and cancer development/progression. Moreover, circadian rhythm consideration in the therapeutic action of anticancer drugs can enhance the effectiveness of cancer therapy. Nanosized drug delivery systems (DDS) have been demonstrated to be suitable engineered platforms for drug targeted/sustained release. The investigation of the chronobiology-nanotechnology relationship, i.e., timing DDS performance according to a patient's circadian rhythm, may greatly improve cancer clinical outcomes. In the present work, we synthesized nanosystems based on an octa-arginine (R8)-modified poly(amidoamine) dendrimer conjugated with the anticancer drug paclitaxel (PTX), G4-PTX-R8, and its physicochemical properties were revealed to be appropriate for in vitro delivery. The influence of the circadian rhythm on its cellular internalization efficiency and potential therapeutic effect on human cervical cancer cells (HeLa) was studied. Cell-internalized PTX and caspase activity, as a measure of induced apoptosis, were monitored for six time points. Higher levels of PTX and caspase-3/9 were detected at T8, suggesting that the internalization of G4-PTX-R8 into HeLa cells and apoptosis are time-specific/-regulated phenomena. For a deeper understanding, the clock protein Bmal1—the main regulator of rhythmic activity, was silenced by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. Bmal1 silencing was revealed to have an impact on both PTX release and caspase activity, evidencing a potential role for circadian rhythm on drug delivery/therapeutic effect mediated by G4-PTX-R8. [ABSTRACT FROM AUTHOR]

Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge. Nanoparticle-based drug delivery systems offer a potential therapeutic strategy; however, the low loading efficiency, non-responsiveness, and single effect of conventional nanoparticles hinder their clinical application. In this study, we designed a novel self-assembled, dual responsive, and dual drug-loading nanocarrier system, which comprised two parts: the hydrophobic lipid core formed by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG) loaded with alpha-lipoic acid (ALA); and a hydrophilic shell comprising a poly (amidoamine) dendrimer (PAMAM) that electrostatically adsorbed minocycline hydrochloride (Mino). This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment. In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions, and ameliorated periodontal bone resorption. This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.

We propose and demonstrate dendrimer-based coatings for a sensitive biochip surface that enhance the high-performance sorption of small molecules (i.e., biomolecules with low molecular weights) and the sensitivity of a label-free, real-time photonic crystal surface mode (PC SM) biosensor. Biomolecule sorption is detected by measuring changes in the parameters of optical modes on the surface of a photonic crystal (PC). We describe the step-by-step biochip fabrication process. Using oligonucleotides as small molecules and PC SM visualization in a microfluidic mode, we show that the PAMAM (poly-amidoamine)-modified chip's sorption efficiency is almost 14 times higher than that of the planar aminosilane layer and 5 times higher than the 3D epoxy-dextran matrix. The results obtained demonstrate a promising direction for further development of the dendrimer-based PC SM sensor method as an advanced label-free microfluidic tool for detecting biomolecule interactions. Current label-free methods for small biomolecule detection, such as surface plasmon resonance (SPR), have a detection limit down to pM. In this work, we achieved for a PC SM biosensor a Limit of Quantitation of up to 70 fM, which is comparable with the best label-using methods without their inherent disadvantages, such as changes in molecular activity caused by labeling. [ABSTRACT FROM AUTHOR]

Contamination of deoxynivalenol (DON) in grains has attracted widespread concern. It is urgently needed to develop a highly sensitive and robust assay for DON high-throughput screening. Antibody against DON was assembled on the surface of immunomagnetic beads orientationally by the aid of Protein G. AuNPs were obtained under the scaffolding of poly(amidoamine) dendrimer (PAMAM). DON-horseradish peroxidase (HRP) was combined on the periphery of AuNPs/PAMAM by a covalent link to develop DON-HRP/AuNPs/PAMAM. Magnetic immunoassay based on DON-HRP/AuNPs/PAMAM was optimized and that based on DON-HRP/AuNPs and DON-HRP was adopted as comparison. The limits of detection (LODs) were 0.447 ng/mL, 0.127 ng/mL and 0.035 ng/mL for magnetic immunoassays based on DON-HRP, DON-HRP/Au and DON-HRP/Au/PAMAM, respectively. Magnetic immunoassay based on DON-HRP/AuNPs/PAMAM displayed higher specificity towards DON and was utilized to analyze grain samples. The recovery for the spiked DON in grain samples was 90.8–116.2% and the method presented a good correlation with UPLC/MS. It was found that the concentration of DON was in the range of ND-3.76 ng/mL. This method allows the integration of dendrimer–inorganic NPs with signal amplification properties for applications in food safety analysis. [ABSTRACT FROM AUTHOR]

Oxanorbornene cored 0.5, 1.5 and 2.5 generation ester terminated PAMAM dendronized monomers with 2 and 6 carbon-containing alkyl spacer in the middle of oxanorbornene core and dendronized branching were synthesized. Monomers were polymerized through the ring-opening metathesis polymerization (ROMP) technique by using 2nd and 3rd generation Grubbs catalysts to get dendronized ROMP polymers. It was found that Grubbs 3rd generation catalyst works well for 0.5 generation dendronized ROMP polymer whereas Grubbs 2nd generation catalyst works for the higher generation. We also found the linker effect during polymerization as six-carbon linker monomers polymerize with high yield along with higher generation. Finally, dendronized ROMP-based PAMAM encapsulated zero valent Cu nanoparticle was synthesized by using a reducing agent, NaBH4. The catalytic activity of this nanoparticle was further investigated from the reduction of 4-nitrophenol to 4-aminophenol. [ABSTRACT FROM AUTHOR]

Here, we aimed to chemically modify PAMAM dendrimers using lysine as a site-selective anchor for successfully delivering mRNA while maintaining a low toxicity profile. PAMAM dendrimers were multi-functionalised by amidation reactions in a regioselective, quantitative and stepwise manner with carefully selected property-modifying surface groups. Alternatively, novel lysine-based dendrimers were prepared in the same manner with the aim to unlock their potential in gene delivery. The modified dendrimers were then formulated with Cy5-EGFP mRNA by bulk mixing via liquid handling robotics across different nitrogen to phosphate ratios. The resulting dendriplexes were characterised by size, charge, mRNA encapsulation, and mRNA binding affinity. Finally, their in-vitro delivery activity was systematically investigated across key cellular trafficking stages to relate chemical design to cellular effect. We demonstrate our findings in different cell lines and benchmarked relative to a commercially available transfection agent, jetPEI®. We demonstrate that specific surface modifications are required to generate small, reliable and well-encapsulated positively charged dendriplex complexes. Furthermore, we show that introduction of fusogenic groups is essential for driving endosomal escape and achieving cellular delivery and translation of mRNA in these cell lines. [Display omitted] • PAMAM & lysine dendrimers were modified with functional groups for mRNA delivery • Automated formulation established optimal mRNA cargo loading conditions • In-vitro testing identified dendrimers with improved endosomal escape, particularly by p-toluylsulfonyl arginine groups • Dendrimers outperformed a commercial standard, jetPEI® • Effective dendrimers for mRNA delivery were well tolerated in vitro. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) (PAMAM) dendrimers are widely studied as drug vectors due to their particular structure and excellent properties. Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface. In this paper, the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs (doxorubicin (DOX), paclitaxel (TAX), hydroxycamptothecin (HCPT)) is studied by molecular dynamics (MD) simulations. Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations, including particle size, drug loading, drug release, and biocompatibility. The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open, and most drug molecules are not completely wrapped. The internal structure of PAMAM dendrimers became looser with more extended nuclei, which increased the non-covalent interactions between PAMAM dendrimers and drug molecules. The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate. This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are versatile nanomaterials that can be used as drug delivery systems and photothermal agents for cancer therapy. In this study, we developed a novel nanoplatform based on AuNPs using a modified one-pot chemical method for the synthesis of AuNPs using generation 3.0 highly branched biphasic polymeric (polyamidoamine) dendrimers as reducing and stabilizing agent, and hyaluronic acid (HA) as functional moiety. Tetrahydrocurcumin (THC) was chosen for this formulation to be encapsulated in the synthesized AuNPs and their efficacy as nanotherapeutics was investigated in vitro. The developed nanoplatform was characterized by various techniques and evaluated for its drug loading and release, cellular uptake, and cytotoxicity on Caco-2 cells. We found that the nanoplatform had optimal size, charge, stability, and solubility, and showed high encapsulation efficiency of THC. The nanoplatform exhibited pH-responsive drug release and enhanced cellular uptake of THC. The nanoplatform also induced apoptosis in Caco-2 cell line. The HA coating on the nanoplatform improved its biocompatibility and specificity, by facilitating its targeting to CD44 glycoprotein on Caco-2 cells. Our results suggest that the developed nanoplatform is a promising nanotherapeutic strategy for cancer therapy by co-delivering of anti-cancer agents and AuNPs to cancer cells.

Neonatal brain injury affects thousands of babies each year and may lead to long-term and permanent physical and neurological problems. Currently, therapeutic hypothermia is standard clinical care for term newborns with moderate to severe neonatal encephalopathy. Nevertheless, it is not completely protective, and additional strategies to restore and promote regeneration are urgently needed. One way to ensure recovery following injury to the immature brain is to augment endogenous regenerative pathways. However, novel strategies such as stem cell therapy, gene therapies and nanotechnology have not been adequately explored in this unique age group. In this perspective review, we describe current efforts that promote neuroprotection and potential targets that are unique to the developing brain, which can be leveraged to facilitate neuroregeneration.

The rheological properties of macromolecules represent one of the fundamental features of polymer systems which expand the possibilities of using and developing new materials based on them. In this work, we studied the shear-stress relaxation of the second generation PAMAM and PPI dendrimer melts by atomistic molecular dynamics simulation. The time dependences of relaxation modulus G(t) and the frequency dependences of the storage G′(ω) and loss G″(ω) moduli were obtained. The results were compared with the similar dependences for the polycarbosilane (PCS) dendrimer of the same generation. The chemical structure of the dendrimer segments has been found to strongly influence their mechanical relaxation. In particular, it has been shown that hydrogen bonding in PAMAM dendrimers leads to an entanglement of macromolecules and the region is observed where G′(ω) > G″(ω). This slows down the mechanical relaxation and rotational diffusion of macromolecules. We believe that our comprehensive research contributes to the systematization of knowledge about the rheological properties of dendrimers. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface. In this study, we successfully conjugated an RRHRH oligopeptide to the surface of PAMAM generation 2 (PAMAM G2) to create RRHRH-PAMAM G2. This construction aims to condense plasmid DNA (pDNA) and facilitate its penetration into cell membranes, leading to its promising potential for gene therapy. RRHRH-PAMAM G2/pDNA complexes were smaller than 100 nm and positively charged. Nano-polyplexes can enter the cell and show a high transfection efficiency after 24 h of transfection. The RRHRH-PAMAM G2 was non-toxic to HeLa, NIH3T3, A549, and MDA-MB-231 cell lines. These results strongly suggest that RRHRH-PAMAM G2 holds promise as a gene carrier for gene therapy owing to its biocompatibility and ability to deliver genes to the cell.

Sensitive detection of ochratoxin A (OTA) is significant and essential because OTA may pose risks to human and animal health. Here, we developed an electrochemical aptasensor for OTA analysis using polyamidoamine (PAMAM) dendrimers as a signal amplifier. As a carrier, PAMAM has numerous primary amino groups that can be coupled with thiolated complementary strand DNA (cDNA), allowing it to recognize aptamers bound to the surface of horseradish peroxidase (HRP)-modified gold nanoparticles (AuNPs), thereby improving the sensitivity of the aptasensor. When monitoring the positive samples, OTA was captured by the aptamer fixed on the HRP-conjugated AuNP surface by specific recognition, after which the formed OTA-aptamer conjugates were detached from the electrode surface, ultimately decreasing the electrochemical signal monitored by differential pulse voltammetry. The novel aptasensor achieved a broad linear detection range from 5 to 105 ng L−1 with a low detection limit of 0.31 ng L−1. The proposed aptasensor was successfully applied for OTA analysis in red wine, with recovery rates ranging from 94.15 to 106%. Furthermore, the aptasensor also exhibited good specificity and storage stability. Therefore, the devised aptasensor represents a sensitive, practical and reliable tool for monitoring OTA in agricultural products, which can also be adapted to other mycotoxins.

Abstract Background Cartilage defects pose a significant burden on medical treatment, leading to an urgent need to develop regenerative medicine approaches for cartilage repair, such as stem cell therapy. However, the direct injection of stem cells can result in insufficient delivery or inaccurate differentiation. Hence, it is necessary to choose appropriate stem cell delivery scaffolds with high biocompatibility, injectability and chondral differentiation induction ability for cartilage regeneration. Methods In this study, the photocrosslinked gelatin methacrylate (GelMA) hydrogel with high cell affinity and plasticity was selected and strengthened by incorporating methacrylic anhydride-modified poly(amidoamine) (PAMAM-MA) to fabricate an adipose-derived stromal/stem cells (ASCs) delivery scaffold for cartilage repair. The physiochemical properties of the GelMA/PAMAM-MA hydrogel, including the internal structure, stability and mechanical properties, were tested. Then, ASCs were encapsulated into the hydrogels to determine the in vitro and in vivo chondrogenic differentiation induction abilities of the GelMA/PAMAM-MA hydrogel. Results Compared with the GelMA hydrogel, the GelMA/PAMAM-MA hydrogel exhibited more uniform structure, stability and mechanical properties. Moreover, on the basis of good biocompatibility, the hybrid hydrogel was proven to exert a sufficient ability to promote cartilage regeneration by in vitro three-dimensional (3D) culture of rASCs and in vivo articular cartilage defect repair. Conclusions The injectable photocrosslinked GelMA/PAMAM-MA hydrogel was proven to be a capable stem cell carrier for cartilage repair and provides new insight into the design strategy of stem cell delivery scaffolds.

A convenient method for the synthesis of the second generation of PAMAM dendrimers based on a p-tert-butylthiacalix[4]arene core in cone, partial cone and 1,3-alternate conformations was developed. Unusual fluorescence of the obtained PAMAM-calix-dendrimers has been found and explained. The binding ability of the synthesized dendrimers toward catecholamines (dopamine, L-adrenaline and L-noradrenaline) was shown by UV-Vis, fluorescence, 1D and 2D NMR spectroscopy and the binding constants (logKa 3.85–4.74) calculated. As was shown, the PAMAM-calix-dendrimers bind catecholamines by the internal cavities. All the studied hormones were most efficiently bound by the dendrimers bearing a macrocyclic core in 1,3-alternate conformation. The size of the formed supramolecular systems of dendrimer/catecholamine was established by the DLS method. A decrease in hemolytic activity of the PAMAM-calix-dendrimers with an increase in the generation number of a dendrimer was shown for the dendrimers with a core in 1,3-alternate conformation. The prospects for the use of the synthesized dendrimers with the macrocyclic core as drug delivery agents were discussed. [ABSTRACT FROM AUTHOR]

The objective of the present work is to evaluate the ability of the radiolabeled PAMAM dendrimers (polyamidoamine) towards facilitating the delivery of an in‐house synthesized porphyrin derivative in the tumorous lesions to evaluate their candidature for possible application in endo‐radionuclide therapy. For this, PAMAM particles were conjugated with a porphyrin derivative namely, 5,10,15,20‐tetrakis‐(4‐carboxymethyleneoxyphenyl)porphyrin (STAP), synthesized in‐house following a two‐step reaction. The average number of porphyrin molecules loaded per PAMAM particle was evaluated using ultraviolet‐visible spectrophotometry and was found to be approximately 2. STAP conjugated PAMAM particles were further conjugated with p‐NCS‐benzyl‐DOTA (subsequently referred as DOTA) to facilitate radiolabeling with 177Lu. On an average, two p‐NCS‐benzyl‐DOTA molecules were observed to be attached per PAMAM‐STAP particle. DOTA‐PAMAM‐STAP conjugate was radiolabeled with 177Lu with a final radiochemical purity of >95%, which was determined by paper chromatography using two different mobile phases viz. 0.1 M sodium citrate buffer (pH 5.0) and 10 mM DTPA. Biological behavior of [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate was investigated in fibrosarcoma bearing Swiss mice model wherein accumulation of radiolabeled particles was observed in liver, GIT, spleen, and kidneys at 3 h post‐administration. However, accumulated activity exhibited rapid clearance from majority of the organs at 24 h post‐administration. [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate exhibited an appreciable uptake in tumor mass [6.09 ± 1.22 percentage injected activity/organ (% IA/organ)] at 3 h post‐administration (p.i.) which was found to reduce to 1.05 ± 0.13 % IA/organ at 24 h post‐administration. The results obtained in biodistribution studies were further corroborated through scintigraphic imaging performed in the same animal model. Despite of an appreciable accumulation in tumor mass, the lower retention of the [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate therein, at longer time point (24 h p.i.) may limit its possible potential as a radio‐therapeutic agent and indicates towards need for further structural manoeuvring to attain favorable in vivo performance. [ABSTRACT FROM AUTHOR]

The novel PAMAM perylene tetracarboxydiimide 5 was synthesized via PAMAM divergent strategy, involves initial Michael addition of aminofunctional core 3 with methyl acrylate followed by exhaustive amidation of the resulting ester 4 with a large excess of ethylenediamine to afford the fluorescent dendrimer 5 with reactive amine groups of its periphery, The chosen fluorophore units are suitable donor–acceptor pair for light-harvesting materials which was in agreement with their good antibacterial activity. [ABSTRACT FROM AUTHOR]

Self-healing alginate hydrogels play important roles in the biological field due to their biocompatibility and ability to recover after cracking. One of the primary targets for researchers in this field is to increase the self-healing speed. Sodium alginate was oxidized, generating aldehyde groups on the chains, which were then crosslinked by poly(amino) amine (PAMAM) via Schiff base reaction. The dendritic structure was introduced to the alginate hydrogel in this work, which was supposed to promote intermolecular interactions and accelerate the self-healing process. Results showed that the hydrogel (ADA-PAMAM) formed a gel within 2.5 min with stable rheological properties. Within 25 min, the hydrogel recovered under room temperature. Furthermore, the aldehyde degree of alginate dialdehyde with a different oxidation degree was characterized through gel permeation chromatograph aligned with multi-angle laser light scattering and ultraviolet (UV) absorption. The chemical structure of the hydrogel was characterized through Fourier transform infrared spectroscopy and UV-vis spectra. The SEM and laser scanning confocal microscope (CLSM) presented the antibiotic ability of ADA-PAMAM against both S. aureus and E. coli when incubated with 10−7 CFU microorganism under room temperature for 2 h. This work presented a strategy to promote the self-healing of hydrogel through forming a dendritic dynamic crosslinking network. [ABSTRACT FROM AUTHOR]

Background: Cartilage defects pose a significant burden on medical treatment, leading to an urgent need to develop regenerative medicine approaches for cartilage repair, such as stem cell therapy. However, the direct injection of stem cells can result in insufficient delivery or inaccurate differentiation. Hence, it is necessary to choose appropriate stem cell delivery scaffolds with high biocompatibility, injectability and chondral differentiation induction ability for cartilage regeneration. Methods: In this study, the photocrosslinked gelatin methacrylate (GelMA) hydrogel with high cell affinity and plasticity was selected and strengthened by incorporating methacrylic anhydride-modified poly(amidoamine) (PAMAM-MA) to fabricate an adipose-derived stromal/stem cells (ASCs) delivery scaffold for cartilage repair. The physiochemical properties of the GelMA/PAMAM-MA hydrogel, including the internal structure, stability and mechanical properties, were tested. Then, ASCs were encapsulated into the hydrogels to determine the in vitro and in vivo chondrogenic differentiation induction abilities of the GelMA/PAMAM-MA hydrogel. Results: Compared with the GelMA hydrogel, the GelMA/PAMAM-MA hydrogel exhibited more uniform structure, stability and mechanical properties. Moreover, on the basis of good biocompatibility, the hybrid hydrogel was proven to exert a sufficient ability to promote cartilage regeneration by in vitro three-dimensional (3D) culture of rASCs and in vivo articular cartilage defect repair. Conclusions: The injectable photocrosslinked GelMA/PAMAM-MA hydrogel was proven to be a capable stem cell carrier for cartilage repair and provides new insight into the design strategy of stem cell delivery scaffolds. [ABSTRACT FROM AUTHOR]

Nanoscale size, a multi-functionalized surface, high branching, a cavernous interior, and other distinctive structural features of dendrimers make them perfect drug delivery systems. In the past forty years, dendrimer research has expanded tremendously from synthesis to use since Fritz Vögtle originally published the first dendrimer in 1978. Nanoscale size, a multi-functionalized surface, high branching, a cavernous interior, and other distinctive structural features of dendrimers make them perfect drug delivery systems. This review focuses on the most recent advancements in the use of dendrimers as drug and gene carriers, including active drug release strategies to release the drug or gene from the dendrimer in response to stimuli, size-adaptive and charge-reversal dendrimer delivery systems that can better utilise the size and surface characteristics of dendrimer bulk and micro/nano dendrimer gel delivery systems, and other recent developments. Recent developments in dendrimer formulations may result in the creation of novel gene and drug products as well as combination medicines. [ABSTRACT FROM AUTHOR]

The oral route is the preferred way of drug administration for most drugs, whose treatment success is directly related to the compound intestinal absorption. This absorption process, in its turn, is influenced by several factors impacting the drug bioavailability, which is extremely dependent on the maximum solubility and permeability. However, optimizing these last two factors, without chemical structural modification, is challenging. Although poly(amidoamine) dendrimers (PAMAM) are an innovative and promising strategy as drug delivery compounds, there are few studies that determine the permeability and solubility of PAMAM-drugs derivatives. Considering this scenario, this paper aimed to carry out a literature review of the last five years concerning biopharmaceutical characterizations of dendrimer delivery systems. In vitro methodologies, such as the Parallel artificial membrane permeability assay (PAMPA) (non-cellular based model) and Caco-2 cells (cellular based model), used for the permeability evaluation in the early stages of drug discovery proved to be the most promising methodologies. As a result, we discussed, for instance, that through the usage of PAMPA it was possible to evaluate the higher capacity for transdermal delivery of DNA of TAT-conjugated PAMAM, when in comparison with unmodified PAMAM dendrimer with a P <0.05. We also presented the importance of choosing the best methods of biopharmaceutical characterization, which will be essential to guarantee the efficacy and safety of the drug candidate. [Display omitted] • Poly(amidoamine) (PAMAM) dendrimers are currently attracting growing interest in the field of nanotechnology and Nanomedicine, especially as drug delivery systems that are capable of enhancing the permeability and solubility of compounds. • The studies of the biopharmaceutical properties employed questionable methodologies when in the development of PAMAM-drugs derivatives. These properties directly affect the bioavailability of the compounds. • In vitro methodologies, such as the parallel artificial membrane permeability assay (PAMPA) and Caco-2 cells, used for the permeability evaluation in the early stages of drug discovery proved to be the most promising methodologies. [ABSTRACT FROM AUTHOR]

Scientists have recently paid a lot of attention to the use of dendrimers in biomedicine. The properties of dendrimers, such as their branching, well-defined globular structures, excellent structural regularity, multivalency, diverse chemical composition, and great biological compatibility, make them appealing for biomedical applications. Several biologically active substances can be incorporated into the three- dimensional structure of dendrimers to create biologically active conjugates. First, a brief overview of dendrimers is given in this state-of-art review, with an emphasis on Poly(amidoamine) (PAMAM) dendrimers and optical sensors. Dendrimers are a newer type of monodisperse polymer with tree-like spherical structures and well-defined sizes and forms. Their peculiar structure significantly affects both their chemical and physical characteristics. PAMAM dendrimer-based optical sensors, employed for the detection of pH, cations, and other analytes, have recently seen advancements, according to reports. Due to its robust synthesis, availability, dendritic structure, and peptide/protein mimic properties, poly(amidoamine) (PAMAM) dendrimers have received the most research attention of all the dendrimers that have been described. The current review is thorough and addresses a different generation of PAMAM dendrimer and related aspects, including i) properties, ii) synthesis, and iii) characterization. The focus is on their uses as well as the state of ongoing medication targeting research at the moment. [ABSTRACT FROM AUTHOR]

Smart hydrogels, owing to their exceptional viscoelastic and deformable capacity in response to environmental stimulation involving temperature and pH, have been successfully applied in oilfields for purposes such as water and/or gas shutoff treatments. However, the CO2 breakthrough problem in low permeability reservoirs has not been well solved. In this work, a rheological method-based Avrami dynamics model and Dickinson dynamics model were employed to investigate the dynamic gelation process of thermo-/pH-dual-sensitive PEG/PAMAM nanogels to further our understanding of the microstructure of their gelation and pertinence plugging application. Plugging experiments were performed by alternating injections of CO2 and hydrogel solution in a slug type on three fractured low permeability cores with a backpressure of 13 MPa. The nanogels presented a secondary growth pattern from three to one dimension from micrometer to nanometer size with a morphological transformation from a sphere to an irregular ellipsoid or disk shape. The phase transition temperature was 50 °C, and the phase transition pH was 10. If both or either were below these values, the hydrogel swelled; otherwise, it shrank. Plugging results show that the plugging efficiency was higher than 99%. The maximum breakthrough pressure was 19.93 MPa, and the corresponding residual pressure remained 17.64 MPa for a 10 mD core, exhibiting great plugging performance and high residual resistance after being broken through by CO2. [ABSTRACT FROM AUTHOR]

Although polyvinyl alcohol (PVA) membranes are commonly used for CO2 separation, there is still large development space in mechanical properties and high selectivity of the gas separation process. In this study, the gas separation performance and mechanical properties of the (PVA/Cu2+) substrate membranes were improved by introducing polyamidoamine (PAMAM). PAMAM had an important effect on the gas adsorption and separation performance of the membrane. In addition, the gas adsorption and separation properties of the PVA/Cu2+/PAMAM membrane (PPCm) were analyzed and studied when the inlet gas pressure and the species of mixed gases were variable. The results showed that the crystallinity and mechanical properties of the membrane with the PAMAM had been significantly improved. Young's modulus of PPCm with 30% PAMAM was 132% higher than that of the PVA/Cu2+ composite membrane without PAMAM. In addition, efficient separation efficiency and high selectivity of the gas separation process were observed. The separation factors of the PPCm for CO2/H2 and CO2/N2 were about three times higher than that of the PVA/Cu2+ substrate membranes. These results suggested that the introduction of PAMAM was promising for CO2 separation and permeance. [ABSTRACT FROM AUTHOR]