Receptor Targeting Using Copolymer-Modified Gold Nanoparticles for pCMV-Luc Gene Delivery to Liver Cancer Cells In Vitro.

The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy.

Chemotherapeutic Activities of New η6-p-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands.

A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiii, 4bi, 4bii), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (5bi, 5civ/6bi, 6ci, 6civ) in the forms [MII(cym)(L)Cl]PF6 and [MII(cym)(L)]PF6 (M = Ru or Os, cym = η6-p-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a "piano-stool" geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds 3aii, 5civ, 5bi, 4aiii, 6ci, 6civ, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds 3ai, 3aiii, 3bii, 4bi, 4bii, and 6bi, which were found not to be selective between normal and tumor cell lines. The IC50 value of the tridentate half-sandwich complex 5bi (86 ± 9 µM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 µM). The pincer (SNS) osmium complexes 6ci (36 ± 10 µM) and 6civ (40 ± 4 µM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex 5civ was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 µM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand's spatial coordination, the nature of the metal center, and the charge of the metal complex ions.

Hydrogels and Wound Healing: Current and Future Prospects.

The care and rehabilitation of acute and chronic wounds have a significant social and economic impact on patients and global health. This burden is primarily due to the adverse effects of infections, prolonged recovery, and the associated treatment costs. Chronic wounds can be treated with a variety of approaches, which include surgery, negative pressure wound therapy, wound dressings, and hyperbaric oxygen therapy. However, each of these strategies has an array of limitations. The existing dry wound dressings lack functionality in promoting wound healing and exacerbating pain by adhering to the wound. Hydrogels, which are commonly polymer-based and swell in water, have been proposed as potential remedies due to their ability to provide a moist environment that facilitates wound healing. Their unique composition enables them to absorb wound exudates, exhibit shape adaptability, and be modified to incorporate active compounds such as growth factors and antibacterial compounds. This review provides an updated discussion of the leading natural and synthetic hydrogels utilized in wound healing, details the latest advancements in hydrogel technology, and explores alternate approaches in this field. Search engines Scopus, PubMed, Science Direct, and Web of Science were utilized to review the advances in hydrogel applications over the last fifteen years.

Curcumin-reduced gold nanoparticles facilitate IL-12 delivery to a cervical cancer in vitro cell model.

Aim: To synthesize curcumin-reduced gold nanoparticles (AuNPs) for the efficient delivery to and expression of the IL-12 gene in cervical cancer (HeLa) cells in vitro. Methods: Curcumin-reduced AuNPs were synthesized, stabilized with poly-L-lysine and PEG, conjugated to IL-12 DNA and physicochemically characterized. Cytotoxicity and IL-12 expression were accessed in vitro. Results & discussion: Stable, spherical AuNPs effectively compacted and protected the IL-12 DNA and tolerated well in vitro. Real-time quantitative PCR and ELISA confirmed the successful delivery and expression of the IL-12 gene in HeLa cells. Conclusion: The favorable attributes of this AuNP-delivery system and the significant IL-12 expression obtained augur well for cytokine-based therapy or immunotherapy in cervical cancer.

Phytochemical Composition and Antibacterial Activity of Barleria albostellata C.B. Clarke Leaf and Stem Extracts.

Barleria albostellata (Acanthaceae) is a shrub located in South Africa and is relatively understudied. However, plants within this genus are well known for their medicinal and ethnopharmacological properties. This study aimed to characterise the phytochemical compounds and antibacterial efficacies of B. albostellata. Phytochemical analysis, fluorescence microscopy and gas chromatography-mass spectrometry (GC-MS) analysis were performed to determine the composition of compounds that may be of medicinal importance. Crude leaf and stem extracts (hexane, chloroform and methanol) were subjected to an antibacterial analysis against several pathogenic microorganisms. The qualitative phytochemical screening of leaf and stem extracts revealed the presence various compounds. Fluorescence microscopy qualitatively assessed the leaf and stem powdered material, which displayed various colours under bright and UV light. GC-MS chromatograms represents 10-108 peaks of various compounds detected in the leaf and stem crude extracts. Major pharmacologically active compounds found in the extracts were alpha-amyrin, flavone, phenol, phytol, phytol acetate, squalene and stigmasterol. Crude extracts positively inhibited Gram-positive and Gram-negative bacteria. Significance was established at p < 0.05 for all concentrations and treatments. These results indicate that the leaves and stems of B. albostellata are rich in bioactive compounds, which could be a potential source of antibacterial agents for treating various diseases linked to the pathogenic bacteria studied. Future discoveries from this plant could advance the use of indigenous traditional medicine and provide novel drug leads.

Development and Biomechanics of Grewia lasiocarpa E. Mey. Ex Harv. Trichomes Exudate.

Grewia lasiocarpa E. Mey. Ex Harv., Malvaceae (forest raisin) is a tropical small tree or shrub valued for its ecological importance as well as its nutritional, antioxidant, antibacterial, and anti-cancer properties as well as its ecological and ornamental importance. Glandular and non-glandular trichomes are present on the fruits, stem bark and leaves of G. lasiocarpa and these trichomes are the first line of defense. They are important structures that plants use to combat biotic and abiotic stress. The development of G. lasiocarpa trichomes and the biomechanics of the exudates present in the glandular (capitate) trichome were investigated for the first time using advanced microscopy techniques [Scanning electron microscope (SEM) and Transmission electron microscope (TEM)]. The pressurized cuticular striations may play a role in the exudates' biomechanics, i.e., releasing secondary metabolites present in the capitate trichome, which was observed to be multidirectional. The presence of many glandular trichomes on a plant implies an increase in the amount of phytometabolites. A common precursor for the development of trichomes (non-glandular and glandular) was observed to be DNA synthesis associated with a periclinal cell division, thus the final fate of the cell is determined by cell cycle regulation, polarity, and expansion. The glandular trichomes of G. lasiocarpa are multicellular and polyglandular, while the non-glandular (glandless) trichomes are either single-celled or multicellular. Since, trichomes 'house' phytocompounds of medicinal, nutritional, and agronomical benefits; the molecular and genetic study of the glandular trichomes of Grewia lasiocarpa will be beneficial to humanity.

Copolymer-Green-Synthesized Copper Oxide Nanoparticles Enhance Folate-Targeting in Cervical Cancer Cells In Vitro.

Cervical cancer is fast becoming a global health crisis, accounting for most female deaths in low- and middle-income countries. It is the fourth most frequent cancer affecting women, and due to its complexity, conventional treatment options are limited. Nanomedicine has found a niche in gene therapy, with inorganic nanoparticles becoming attractive tools for gene delivery strategies. Of the many metallic nanoparticles (NPs) available, copper oxide NPs (CuONPs) have been the least investigated in gene delivery. In this study, CuONPs were biologically synthesized using Melia azedarach leaf extract, functionalized with chitosan and polyethylene glycol (PEG), and conjugated to the targeting ligand folate. A peak at 568 nm from UV-visible spectroscopy and the characteristic bands for the functional groups using Fourier-transform infrared (FTIR) spectroscopy confirmed the successful synthesis and modification of the CuONPs. Spherical NPs within the nanometer range were evident from transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The NPs portrayed exceptional binding and protection of the reporter gene, pCMV-Luc-DNA. In vitro cytotoxicity studies revealed cell viability >70% in human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa) cells, with significant transgene expression, obtained using the luciferase reporter gene assay. Overall, these NPs showed favorable properties and efficient gene delivery, suggesting their potential role in gene therapy.

Antioxidant and Antibacterial Activities of the Leaf and Stem Extracts of Combretum molle (R. Br. ex G. Don.) Engl. & Diels.

Medicinal plants offer reasonable and accessible alternatives to synthetic drugs and are often devoid of the adverse side effects, toxicity, and pathogenic resistance associated with synthetic medicine. Combretum molle has been utilized in African traditional medicinal practices and purportedly contains bioactive compounds with medicinally beneficial effects. This study investigated the hexane, chloroform, and methanol leaf and stem extracts for their antioxidant properties using the 2,2'-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing antioxidant power assays. The study additionally analyzed the methanol extracts for their antibacterial activity against Gram-negative Escherichia coli (ATCC 25922) and Gram-positive Staphylococcus aureus (ATCC 25923) bacteria using agar well diffusion. Relative to the scavenging activity of the ascorbic acid control (79.15 ± 0.63% at 15 µg/mL to 94.61 ± 0.12% at 240 µg/mL), the plant's radical scavenging activities were exceptionally high in the methanolic leaf and stem extracts (p < 0.05), ranging from 94.58 ± 1.10% at 15 µg/mL to 99.22 ± 0.30% at 240 µg/mL and 91.57 ± 1.71% at 15 µg/mL to 99.60 ± 0.20% at 240 µg/mL, respectively, suggesting a strong capacity to donate hydrogen ions. High scavenging activities were additionally observed in the chloroform stem (78.68 ± 1.18% at 15 µg/mL to 98.14 ± 1.22% at 240 µg/mL) and hexane leaf (72.12 ± 4.38% at 15 µg/mL to 89.87 ± 1.50% at 240 µg/mL) extracts (p < 0.05). All extracts exhibited poor ferric-reducing abilities in relation to the gallic acid control (100 ± 0.00%) at all concentrations (p < 0.05). The leaf and stem extracts exhibited broad-spectrum antibiotic capabilities against both tested strains, with significant activity at higher concentrations (p < 0.05). Overall, both the leaf and stem extracts of C. molle exhibited similar antioxidant and antibacterial activities. These findings warrant further pharmacological research on C. molle for potential drug development.

Synthesis, Characteristation and Biological Activity of Silver Nanoparticles Generated Using the Leaf and Stembark Extract of Combretum erythrophyllum.

BACKGROUND: Medicinal plants are known to contain numerous phytometabolites with suggested pharmacological value. Literature suggests that the medicinal use of phytometabolites in its natural state has limited success due to poor absorption rates. Currently, the focus lies on synthesizing phytometabolites extracted from medicinal plants and silver ions to generate nano-scale carriers with specialized properties. Thus, the nano-synthesis of phytometabolites with silver (Ag+) ions is proposed. The use of silver is promoted due to its known antibacterial and antioxidant effectiveness, among many. Nanotechnology allows for the green generation of nano-scaled particles that are able to penetrate target areas due to its size and unique structure. Therefore, this study aimed to generate a novel protocol for the synthesis of AgNP's using the leaf and stembark extracts of C. erythrophyllum. In addition, the biological activity of the generated nanoparticles was evaluated. OBJECTIVES: To synthesis silver nanoparticles (AgNP's) using the leaf and stembark extracts of Combretum erythrophyllum. The relative shape, size, distribution, and zeta potential of the synthesised particles were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Energy-dispersive X-ray (EDX), Nanoparticle tracking analysis (NTA), and UV Spectrophotometry (UV -vis). To screen the synthesised particles for its potential antibacterial, apoptotic and cytotoxic properties. METHODS: A novel protocol for the synthesis of silver nanoparticles (AgNP's) using the leaf and stembark extracts of Combretum erythrophyllum was established. The generated AgNP's were characterised using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Energy-dispersive X-ray (EDX), Nanoparticle tracking analysis (NTA), and UV Spectrophotometry (UV -vis). Furthermore, the AgNP's were evaluated for their antibacterial, cytotoxic and apoptotic activity against a range of bacterial strains and cancer cells. Characterisation was based upon particle size, shape and elemental silver composition. RESULTS: Within the stembark extract, synthesised nanoparticles were large, spherical in shape and dense in elemental silver composition. While synthesised nanoparticles of the leaf extract were small to medium in size, varied in shape established and contained minimal quantities of silver (substantiated by the TEM and NTA results). Furthermore, it was established that the synthesized nanoparticles exhibited high antibacterial properties due to the conducted antibacterial assay. The FTIR analysis revealed the presence of numerous functional groups within active compounds found in the synthesised extracts. Functional groups found varied between the leaf and stembark extracts, each with proposed pharmacological activity. CONCLUSION: Presently, antibiotic-resistant bacteria are continuously evolving thus, posing as a threat to conventional drug delivery systems. Nanotechnology provides a platform that enables the formulation of a low-toxicity and hypersensitive drug delivery system. Further studies evaluating the biological activity of extracts of C. erythrophyllum synthesized with silver nanoparticles could enhance its proposed pharmaceutical value.

HER2/neu Oncogene Silencing in a Breast Cancer Cell Model Using Cationic Lipid-Based Delivery Systems.

The overexpression of the human epidermal growth factor 2 (HER2/neu) oncogene is predictive of adverse breast cancer prognosis. Silencing the HER2/neu overexpression using siRNA may be an effective treatment strategy. Major requirements for siRNA-based therapy are safe, stable, and efficient delivery systems to channel siRNA into target cells. This study assessed the efficacy of cationic lipid-based systems for the delivery of siRNA. Cationic liposomes were formulated with equimolar ratios of the respective cholesteryl cytofectins, 3ß-N-(N', N'-dimethylaminopropyl)-carbamoyl cholesterol (Chol-T) or N, N-dimethylaminopropylaminylsuccinylcholesterylformylhydrazide (MS09), with the neutral helper lipid, dioleoylphosphatidylethanolamine (DOPE), with and without a polyethylene glycol stabilizer. All cationic liposomes efficiently bound, compacted, and protected the therapeutic siRNA against nuclease degradation. Liposomes and siRNA lipoplexes were spherical, <200 nm in size, with moderate particle size distributions (PDI < 0.4). The siRNA lipoplexes exhibited minimal dose-dependent cytotoxicity and effective HER2/neu siRNA transfection in the HER2/neu overexpressing SKBR-3 cells. The non-PEGylated Chol-T-siRNA lipoplexes induced the highest HER2/neu silencing at the mRNA (10000-fold decrease) and protein levels (>111.6-fold decrease), surpassing that of commercially available Lipofectamine 3000 (4.1-fold reduction in mRNA expression). These cationic liposomes are suitable carriers of HER2/neu siRNA for gene silencing in breast cancer.

Phytochemical Composition of Combretum molle (R. Br. ex G. Don.) Engl. & Diels Leaf and Stem Extracts.

The demand for medicinal plants is on a rise due to their affordability, accessibility and relatively non-toxic nature. Combretum molle (Combretaceae) is used in African traditional medicine to treat a number of diseases. This study aimed to screen the phytochemical composition of the hexane, chloroform and methanol extracts of C. molle leaves and stems using qualitative phytochemical screening. Additionally, the study aimed to identify the functional phytochemical groups, determine the elemental composition and provide a fluorescence characterization of the powdered leaves and stems by performing Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray (EDX) microanalyses and fluorescence microscopy. Phytochemical screening revealed the presence of alkaloids, flavonoids, phenolic compounds, polyphenols, terpenoids, tannins, coumarins, saponins, phytosterols, gums, mucilage, carbohydrates, amino acids and proteins within all leaf and stem extracts. Lipids and fixed oils were additionally present within the methanol extracts. FTIR demonstrated significant peaks in absorption frequency in the leaf at wavelengths of 3283.18, 2917.81, 1617.72, 1318.83, 1233.97, 1032.32 and 521.38 cm-1, and in the stem at 3318.91, 1619.25, 1317.13, 1032.68, 780.86 and 516.39 cm-1. These corresponded to the functional groups of chemical compounds including alcohols, phenols, primary amines, alkyl halides, alkanes and alkyl aryl ethers, corroborating the presence of the detected phytochemicals within the plant. EDX microanalyses showed the elemental composition of the powdered leaves (68.44% C, 26.72% O, 1.87% Ca, 0.96% Cl, 0.93% Mg, 0.71% K, 0.13% Na, 0.12 % Mn and 0.10% Rb) and stems (54.92% C, 42.86% O, 1.7% Ca, 0.43% Mg and 0.09% Mn). Fluorescence microscopy provided a characteristic evaluation of the plant in its powdered form and revealed distinct colour changes in the material when treated with various reagents and viewed under ultraviolet light. In conclusion, the phytochemical constituents of the leaves and stems of C. molle confirm the suitability of this species for use in traditional medicine. The findings from this study suggest the need to validate the use of C. molle in the development of modern medicines.

Dendrimers as Modifiers of Inorganic Nanoparticles for Therapeutic Delivery in Cancer.

The formulation of nanoscale systems with well-defined sizes and shapes is of great interest in applications such as drug and gene delivery, diagnostics and imaging. Dendrimers are polymers that have attracted interest due to their size, shape, branching length, amine density, and surface functionalities. These unique characteristics of dendrimers set them apart from other polymers, their ability to modify nanoparticles (NPs) for biomedical applications. Dendrimers are spherical with multiple layers over their central core, each representing a generation. Their amphiphilic nature and hollow structure allow for the incorporation of multiple drugs or genes, in addition to enabling easy surface modification with cellular receptor-targeting moieties to ensure site-specific delivery of therapeutics. Dendrimers are employed in chemotherapeutic applications for the delivery of anticancer drugs. There are many inorganic NPs currently being investigated for cancer therapy, each with their own unique biological, chemical, and physical properties. To favor biomedical applications, inorganic NPs require suitable polymers to ensure stability, biodegradability and target specificity. The success of dendrimers is dependent on their unique structure, good bioavailability and stability. In this review, we describe the properties of dendrimers and their use as modifiers of inorganic NPs for enhanced therapeutic delivery. Herein, we review the significant developments in this area from 2015 to 2022. Databases including Web of Science, Scopus, Google Scholar, Science Direct, BioMed Central (BMC), and PubMed were searched for articles using dendrimers, inorganic nanoparticles and cancer as keywords.

Shape memory and antibacterial chitosan-based cryogel with hemostasis and skin wound repair.

Massive damage to the skin can lead to heavy bleeding and potential wound infection. Therefore, the preparation of low-cost wound dressings that meet these requirements by simple methods has a good application prospect. In the study, a shape memory cryogel prepared at low temperatures by mixing chitosan (CS) and citric acid (CA). Silver nanoparticles (Ag NPs) introduced into the cryogel through the reduction of Ag+ with tannic acid (TA) as a reducing agent. The CS/CA/Ag cryogel has good mechanical properties and interconnected macroporous structures. The results of hemostasis tests show that CS/CA/Ag cryogel can absorb a large amount of blood and promote blood cell adhesion compared with commercial gelatin sponges and gauze. Meanwhile, CS/CA/Ag cryogel has a good antibacterial ability against S. aureus and E. coli. Furthermore, CS/CA/Ag cryogel significantly promotes wound healing in the full-thickness wound model infected with S. aureus. In conclusion, the cryogel prepared by the simple method has great advantages in rapid hemostasis and promoting wound healing.

The Potential of Curcumin-Capped Nanoparticle Synthesis in Cancer Therapy: A Green Synthesis Approach.

Cancer nanotherapeutics is an important field of research which utilizes nanomaterials as an approach to cancer therapy. Nano-mediated therapeutic delivery systems overcome the adverse side effects of traditional cancer treatment methods. Nanoparticles (NPs) are considered excellent tumor-targeting vehicles due to their compact and variable size, large surface area, ability to load several genes and drugs, and mediation of increased therapeutic payload uptake. Despite the rapid development of nanotechnology, there is growing concern regarding the possible long-term side effects of NPs on the environment and human health. Green chemistry using plant materials, such as curcumin, is a sustainable alternative to conventional reduction methods and confers dual reducing and capping properties. Curcumin is a bioactive compound isolated from the rhizome of the Curcuma longa plant, which exhibits various medicinal properties. Curcumin-capped NPs exhibit increased solubility, bioavailability, therapeutic indices, and antitumor properties. This review highlights the potential and antitumor properties of economical, simple, and eco-friendly curcumin-synthesized and capped NPs for the localized delivery of therapeutic genes and drugs to the cancer tumor microenvironment with fewer adverse side effects.

Physico-chemical characteristics and cytotoxicity evaluation of CuO and TiO2 nanoparticles biosynthesized using extracts of Mucuna pruriens utilis seeds.

The green synthesis approach to nanoparticles has been widely received as an alternative to the conventional methods, specifically for applications in areas such as biology, agriculture and medicine, where toxicity is of great concern. In this study, copper oxide (CuO) and titanium oxide (TiO2) nanoparticles (NPs) were synthesized using an aqueous extract of Mucuna pruriens utilis seed. The morphology and structural characterization of the NPs were achieved by using scanning and transmission electron microscopy (SEM and TEM), and X-ray diffraction (XRD) measurement, while the elemental composition was studied using electron diffraction X-ray spectroscopy (EDS). A monoclinic phase of CuO and anatase phases of TiO2 with high crystallinity were confirmed from the diffraction patterns of the XRD. Both TEM and SEM micrographs of the CuO confirmed short rod-shaped nanostructure, while spherical morphologies were obtained for the TiO2 NPs. The EDS study indicated that the composition of the samples conformed with the identified products in the XRD and attest to the purity of the NPs. The nanoparticles exhibited a dose-dependent profile in MTT cytotoxicity assay with some cell specificity. However, the anticancer potential of these NPs was still lower than that of the standard anticancer drug, 5-fluorouracil.

Lipid Nanoparticles: Promising Treatment Approach for Parkinson's Disease.

Parkinson's disease (PD), a neurodegenerative disorder, is a life-altering, debilitating disease exhibiting a severe physical, psychological, and financial burden on patients. Globally, approximately 7-10 million people are afflicted with this disease, with the number of cases estimated to increase to 12.9 million by 2040. PD is a progressive movement disorder with nonmotor symptoms, including insomnia, depression, anxiety, and anosmia. While current therapeutics are available to PD patients, this treatment remains palliative, necessitating alternative treatment approaches. A major hurdle in treating PD is the protective nature of the blood-brain barrier (BBB) and its ability to limit access to foreign molecules, including therapeutics. Drugs utilized presently are nonspecific and administered at dosages that result in numerous adverse side effects. Nanomedicine has emerged as a potential strategy for treating many diseases. From the array of nanomaterials available, lipid nanoparticles (LNPs) possess various advantages, including enhanced permeability to the brain via passive diffusion and specific and nonspecific transporters. Their bioavailability, nontoxic nature, ability to be conjugated to drugs, and targeting moieties catapult LNPs as a promising therapeutic nanocarriers for PD. While PD-related studies are limited, their potential as therapeutics is evident in their formulations as vaccines. This review is aimed at examining the roles and properties of LNPs that make them efficient therapeutic nanodelivery vehicles for the treatment of PD, including therapeutic advances made to date.

Carbon-based Nanomaterials for delivery of small RNA molecules: a focus on potential cancer treatment applications.

BACKGROUND: Nucleic acid-mediated therapy holds immense potential in the treatment of recalcitrant human diseases such as cancer. This is underscored by advances in understanding the mechanisms of gene regulation. In particular, the endogenous protective mechanism of gene silencing known as RNA interference (RNAi) has been extensively exploited. METHODS: We review here the developments from 2011 to 2021, in the use of nanographene oxide, carbon nanotubes, fullerenes, carbon nanohorns, carbon nanodots and nanodiamonds for the delivery of therapeutic small RNA molecules. RESULTS: Appropriately designed effector molecules such as small interfering RNA (siRNA), can, in theory, silence the expression of any disease-causing gene. Alternatively, siRNA can be generated in vivo through the introduction of plasmid-based short hairpin RNA (shRNA) expression vectors. Other small RNAs such as micro RNA (miRNA) also function in post-transcriptional gene regulation and are aberrantly expressed under disease conditions. The miRNA-based therapy involves either restoration of miRNA function through the introduction of miRNA mimics; or the inhibition of miRNA function by delivering anti-miRNA oligomers. However, the large size, hydrophilicity, negative charge and nuclease-sensitivity of nucleic acids necessitate an appropriate carrier for their introduction as medicine into cells. CONCLUSION: While numerous organic and inorganic materials have been investigated for this purpose, the perfect carrier agent remains elusive. In recent years, carbon-based nanomaterials have received widespread attention in biotechnology due to their tunable surface characteristics, mechanical, electrical, optical and chemical properties.

Localized Nano-mediated Interleukin-12 Gene Therapy: Promising Candidate for Cancer Immunotherapeutics.

BACKGROUND: Interleukin-12 (IL-12) has a pleiotropic nature that allows it to induce immune responses while reversing tumour-induced immunosuppression. Therefore, this paper discusses the application and potential of IL-12 as an antitumor immunotherapeutic agent, emphasizing its advantages and limitations and the need for and the development of localized IL-12 nano-delivery strategies in cancer immunotherapy. METHODS: Several databases from the National Centre for Biotechnology Information, WorldCat.org and the National Library of Medicine were searched for peer-reviewed studies to assess the potential of localized nano-mediated interleukin-12 gene therapy for cancer treatment. RESULTS: The literature search showed that IL-12 is a promising cancer immunotherapeutic agent. However, the systemic delivery of IL-12 was compromised by severe dose-limiting side effects, prompting the need for localized gene therapy to express the interleukin within the tumour microenvironment while minimizing systematic exposure. Although viral and non-viral gene therapy have demonstrated some efficacy in preclinical trials, the era of nanomedicine has opened novel avenues to improve therapeutic indices with minimal side effects. IL-12 activity can be further potentiated with other anticancer molecules that display immunostimulatory, autoantigenic and cytotoxic properties. Combination therapy has gained significant interest in the last decade as it increases gene therapy's therapeutic properties by decreasing the threshold for IL-12 efficacy and preventing systematic toxicity. CONCLUSION: The findings of this article will provide researchers with the knowledge to create immunotherapeutic nanovectors which work synergistically with their therapeutic payload to enhance the therapeutic effect of the IL-12 gene to eliminate cancer cells.

Advances in the Synthesis and Application of Magnetic Ferrite Nanoparticles for Cancer Therapy.

Cancer is among the leading causes of mortality globally, with nearly 10 million deaths in 2020. The emergence of nanotechnology has revolutionised treatment strategies in medicine, with rigorous research focusing on designing multi-functional nanoparticles (NPs) that are biocompatible, non-toxic, and target-specific. Iron-oxide-based NPs have been successfully employed in theranostics as imaging agents and drug delivery vehicles for anti-cancer treatment. Substituted iron-oxides (MFe2O4) have emerged as potential nanocarriers due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. Current research explores their potential use in hyperthermia and as drug delivery vehicles for cancer therapy. Significantly, there are considerations in applying iron-oxide-based NPs for enhanced biocompatibility, biodegradability, colloidal stability, lowered toxicity, and more efficient and targeted delivery. This review covers iron-oxide-based NPs in cancer therapy, focusing on recent research advances in the use of ferrites. Methods for the synthesis of cubic spinel ferrites and the requirements for their considerations as potential nanocarriers in cancer therapy are discussed. The review highlights surface modifications, where functionalisation with specific biomolecules can deliver better efficiency. Finally, the challenges and solutions for the use of ferrites in cancer therapy are summarised.

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review.

Nanotechnology has opened up a world of possibilities for the treatment of brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver a variety of therapeutic agents, including drugs and nucleic acids. Nanoparticles may also be formulated to contain photosensitizers or, on their own, serve as photothermal conversion agents for phototherapy. Furthermore, nano-delivery agents can enhance the efficacy of contrast agents for improved brain imaging and diagnostics. However, effective nano-delivery to the brain is seriously hampered by the formidable blood-brain barrier (BBB). Advances in understanding natural transport routes across the BBB have led to receptor-mediated transcytosis being exploited as a possible means of nanoparticle uptake. In this regard, the oligopeptide Angiopep-2, which has high BBB transcytosis capacity, has been utilized as a targeting ligand. Various organic and inorganic nanostructures have been functionalized with Angiopep-2 to direct therapeutic and diagnostic agents to the brain. Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson's disease, and Alzheimer's disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders.