Targeted delivery of interleukin-12 plasmid into HepG2 cells through folic acid conjugated graphene oxide nanocarrier.

Successful gene therapy relies on carriers to transfer genetic materials with high efficiency and low toxicity in a targeted manner. To enhance targeted cell binding and uptake, we developed and synthesized a new gene delivery vector based on graphene oxide (GO) modified by branched polyethyleneimine (BPEI) and folic acid (FA). The GO-PEI-FA nanocarriers exhibit lower toxicity compared to unmodified PEI, as well as having the potential to efficiently condense and protect pDNA. Interestingly, increasing the polymer content in the polyplex formulation improved plasmid transfer ability. Substituting graphene oxide for PEI at an N/P ratio of 10 in the HepG2 and THP1 cell lines improved hIL-12 expression by up to approximately eightfold compared to simple PEI, which is twice as high as GO-PEI-FA in Hek293 at the same N/P ratio. Therefore, the GO-PEI-FA described in this study may serve as a targeting nanocarrier for the delivery of the hIL-12 plasmid into cells overexpressing folic acid receptors, such as those found in hepatocellular carcinoma.

Evaluation of Compounded Transdermal Analgesic Formulations Using the Franz Finite Dose Model.

To evaluate the transdermal delivery of six analgesic drugs (i.e., ketamine, gabapentin, clonidine, lidocaine, ketoprofen, and amitriptyline) that were compounded into three commercially available bases, Salt Stable LS Base, Transdermal Pain Base, and Lipoderm ActiveMax Base, the Franz finite dose model was used for an in vitro penetration study using porcine skin over 48 hours. Rapid penetration with a steady-state flux after the first 24 hours was detected in all the formulations. The present study demonstrates the successful delivery of six compounded analgesic drugs, using all of the noted bases. A high flux rate within 1 hour to 4 hours of application would correlate to effective pain relief, and the prolonged delivery over the first 24 hours would reduce the need for frequent reapplication. This can aid in pain management with the potential for enhanced pain control.

Folic Acid-Functionalized Albumin/Graphene Oxide Nanocomposite to Simultaneously Deliver Curcumin and 5-Fluorouracil into Human Colorectal Cancer Cells: An In Vitro Study.

Background: Nowadays, due to various inherent properties, graphene-based nanoparticles are widely used in drug delivery research. On the other hand, folate receptors are highly expressed on the surface of human tumor cells. In this work, to enhance the 5-fluorouracil (5FU) and curcumin (Cur) effects on colon cancer, we constructed a folic acid- (FA-) modified codelivery carrier based on graphene nanoparticles (GO-Alb-Cur-FA-5FU). Materials and Methods: The HUVEC and HT-29 were selected for evaluating the antitumor effect of the prepared nanocarriers. The structure of nanocarriers was characterized by FTIR spectroscopy, X-ray diffraction analysis, TEM microscopy, and a DLS analyzer. The efficiency of the prepared carrier was evaluated by fluorescence microscopy using Annexin V and the PI kit. The cytotoxicity of the carrier's component individually and the efficacy of the drug carrier GO-Alb-Cur-FA-5FU were assessed by MTT. Results: The results of the pharmacological tests indicated that the new nanoparticles cause increased apparent toxicity in HT-29 cells. The apoptosis rate of the HT-29 and HUVEC cells treated with IC50 values of GO-Alb-Cur-FA-5FU for 48 h was higher than the cells treated with IC50 values of 5FU and Cur individually, which indicated the greater inhibitory efficacy of GO-Alb-Cur-FA-5FU than free drugs. Conclusion: The designed GO-Alb-CUR-FA-5FU delivery system can be applied for targeting colon cancer cells and can be severe as a potential candidate for future drug development.

Unpacking Phthalates from Obscurity in the Environment.

Phthalates (PAEs) are a group of synthetic esters of phthalic acid compounds mostly used as plasticizers in plastic materials but are widely applied in most industries and products. As plasticizers in plastic materials, they are not chemically bound to the polymeric matrix and easily leach out. Logically, PAEs should be prevalent in the environment, but their prevalence, transport, fate, and effects have been largely unknown until recently. This has been attributed, inter alia, to a lack of standardized analytical procedures for identifying them in complex matrices. Nevertheless, current advancements in analytical techniques facilitate the understanding of PAEs in the environment. It is now known that they can potentially impact ecological and human health adversely, leading to their categorization as endocrine-disrupting chemicals, carcinogenic, and liver- and kidney-failure-causing agents, which has landed them among contaminants of emerging concern (CECs). Thus, this review article reports and discusses the developments and advancements in PAEs' standard analytical methods, facilitating their emergence from obscurity. It further explores the opportunities, challenges, and limits of their advancements.

Intercalation of curcumin into liposomal chemotherapeutic agent augments apoptosis in breast cancer cells.

Resistance to common chemotherapeutic agents is a frequent phenomenon in late-stage breast cancers. An ideal system capable of the co-delivery of hydrophobic and hydrophilic chemotherapeutic agents can regulate the dosage and co-localization of pharmaceutical compounds and thereby improve the anticancer efficacy. Here, for the first time, we have intercalated curcumin (Cur) into a double-layered membrane of cisplatin (Cis) liposomes to obtain a dosage controlled co-delivery formulation, capable of inducing apoptosis in breast cancer cells. The concentrations of Cur and Cis in nanoliposome (Cur-Cis@NLP) were optimized by response surface methodology (RSM); RSM optimization showed 99.81 and 23.86% entrapment efficiency for Cur and Cis, respectively. TEM analysis demonstrated the fabrication of nanoparticles with average diameter of 100 nm. The anticancer and apoptotic effects of Cur-Cis@NLPs were also evaluated using MTT assay, fluorescent staining and flow cytometry assays. Cytotoxicity assessments of various Cur-Cis@NLPs concentrations demonstrated a concentration-dependent manner. In comparison to free and liposomal Cis, Cur-Cis@NLP reduced breast cancer cells' viability (82.5%) in a significant manner at a final concentration of 32 µg.mL-1 and 20 µg.mL-1 of Cur and Cis, respectively. Combination index values calculation of Cur-Cis@NLP showed an overall CI value <1, indicating synergetic effect of the designed co-delivery system. Additionally, flow cytometry assay demonstrated Cur-Cis@NLPs triggered apoptosis about 10-folds higher than liposomal Cis. This co-drug delivery system has a potential for the encapsulation and release of both hydrophobic and hydrophilic drugs, while taking the advantages of the reduced cytotoxic effect along with achieving high potency.

Recent progress in biomedical applications of RGD-based ligand: From precise cancer theranostics to biomaterial engineering: A systematic review.

Arginine-glycine-aspartic acid (RGD) peptide family is known as the most prominent ligand for extracellular domain of integrin receptors. Specific expression of these receptors in various tissue of human body and tight association of their expression profile with various pathophysiological conditions made these receptors a suitable targeting candidate for several disease diagnosis and treatment as well as regeneration of various organs. For these reasons, various forms of RGD-based integrins ligands have been greatly used in biomedical studies. Here, we summarized the last decade application progress of RGD for cancer theranostics, control of inflammation, thrombosis inhibition and critically discussed the effect of RGD peptides structure and sequence on the efficacy of gene/drug delivery systems in preclinical studies. Furthermore, we will show recent advances in application of RGD functionalized biomaterials for various tissue regenerations including cornea repair, artificial neovascularization and bone tissue regeneration. Finally, we analyzed clinically translatability of RGD peptides, considering examples of integrin ligands in clinical trials. In conclusion, prospects on using RGD peptide for precise drug delivery and biomaterial engineering are well discussed.

A novel theranostic system of AS1411 aptamer-functionalized albumin nanoparticles loaded on iron oxide and gold nanoparticles for doxorubicin delivery.

Recently DNA aptamers have attracted remarkable attention as possible targeting ligands since selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. Here, the development of AS1411 aptamer-functionalized albumin nanoparticles loaded on iron oxide and gold nanoparticles is reported for target delivery of the well-known anticancer drug of doxorubicin (Dox). Iron oxide nanoparticles (IONPs) and gold nanoparticles (GNPs) were prepared by ultrasound-assisted and controlled seeded growth synthetic methods, respectively. The nanocarrier was synthesized by a desolvation cross-linking method and characterized by dynamic light scattering, zeta potential measurement, thermogravimetric analysis, transmission electron microscopy, as well as vibrating sample magnetometer. The synthesized nanoparticles were found to be spherical with an average diameter of 120 nm and zeta potential of about -50.3 mV. The in-vitro anti-tumor effect of the designed delivery vehicle on MCF7 and SKBR3 human cancer cells was evaluated by MTT assay. The experimental results revealed that it could significantly inhibit the proliferation of cancerous cells. Moreover, GNPs and IONPs with the coating of albumin did not show any toxicity. AS1411 aptamer-functionalized nanoparticles improved cellular uptake and efficiency to MCF7 breast cancer cells as compared to non-targeting nanoparticles because of the high affinity of mentioned aptamer toward the overexpressed nucleolin on MCF7 cell surface.