Many macromolecular antitumor drugs were developed based on the enhanced permeability and retention (EPR) effect, for example, albumin-bound paclitaxel nanoparticles (nab-PTX and Abraxane) and pegylated liposomal doxorubicin (Doxil). However, these EPR effect-based therapeutic systems are less effective in malignant tumors with low vascular permeability, such as pancreatic tumors. Because the EPR effect depends on nanoparticles' size, we first determined nanoparticles' size associated with a high tumor-targeting rate in a human pancreatic tumor xenograft model with low vascular permeability. Abraxane appears to behave as an albumin monomer (7 nm) in the blood circulation following intravenous injection. The in vitro and in vivo tumor-targeted delivery and antitumor activity of PTX-loaded albumin nanoparticles were significantly improved by optimizing the mean nanoparticle diameter to 30 nm. Furthermore, nitric oxide was added to 30 nm PTX-loaded albumin nanoparticles to examine the feasibility of albumin nanoparticles as a platform for multiple drug delivery. Their antitumor effect was evaluated in an orthotopic transplantation mouse model of a human pancreatic tumor. The nitric oxide PTX-loaded 30 nm albumin nanoparticle treatment on model mice achieved a significantly higher survival rate than Abraxane treatment. These findings suggest that 30 nm albumin nanoparticles have a high therapeutic effect as a useful platform for multiple drugs against human pancreatic tumors.
Lipid-based biocompatible ionic liquids (LBILs) have attracted attention as carriers in transdermal drug delivery systems (TDDSs) because of their lipophilic character. In this study, we report the formulation of a peptide-LBIL complex microencapsulated in an oil phase as a potential carrier for the transdermal delivery of leuprolide acetate as a model hydrophilic peptide. The peptide-LBIL complexes were prepared via a water-in-oil emulsion composed of 1,2-dimyristoyl-sn-glycerol-3-ethyl-phosphatidylcholine (EDMPC), a fatty acid (stearic, oleic, and linoleic acid)-based LBIL, and cyclohexane followed by freeze-drying to remove the water and cyclohexane. Then, the peptide-LBIL complexes were nanodispersed and stabilized in isopropyl myristate (IPM) using sorbitol laurate (Span-20). Ionic-liquid-in-oil nanodispersions (IL/O-NDs) were prepared with varying weight ratios of LBILs and Span-20 as the surfactant and the cosurfactant, respectively. Keeping the overall surfactant constant at 10 wt % in IPM, a 5:5 wt % ratio of surfactant (IL) and cosurfactant (Span-20) in the IL/O-NDs significantly (p < 0.0001) increased the physiochemical stability, drug-loading capacity, and drug encapsulation efficiency. The in vitro and in vivo peptide delivery across the skin was increased significantly (p < 0.0001) using IL/O-NDs, compared with non-IL-treated groups. Of all of the LBIL-based formulations, [EDMPC][Linoleate]/O-ND was considered the most preferable for a TDDS based on the pharmacokinetic parameters. The transdermal delivery flux with [EDMPC][Linoleate]/O-ND was increased 65-fold compared with the aqueous delivery vehicle. The IL/O-NDs were able to deform the lipid and protein arrangements of the skin layers to enhance the transdermal permeation of the peptide. In vitro and in vivo cytotoxicity studies of the IL/O-NDs revealed the biocompatibility of the LBIL-based formulations. These results indicated that IL/O-NDs are promising biocompatible carriers for lipid-peptide TDDSs.
Quaternary Trimethyl Chitosan (QTMC) and QTMC-Silver Nanoparticles (QTMC-AgNPs) have been synthesized, characterized, and tested as antibacterial agents against Staphylococcus aureus, Escherichia coli, and two plant fungi (Sclerotium rolfsil and Fusarium oxysporum). The as-prepared water-soluble QTMC was in situ reacted with silver nitrate in the presence of clean compressed hydrogen gas (3 bar) as a reducing agent to produce QTMC-AgNPs. UV-vis, ATR-FTIR, HR-TEM/SEM, XPS, DLS, XRD, and TGA/DTG were employed to assess the optical response, morphology/size, surface chemistry, particle size distribution, crystal nature, and thermal stability of the synthesized QTMC-AgNPs, respectively. The as-prepared QTMC-AgNPs were quasi-spherical in shape with an average particle size of 12.5 nm, as determined by ImageJ software utilizing HR-TEM images and further validated by DLS analysis. The development of crystalline nanoparticles was confirmed by the presence of distinct and consistent lattice fringes with an approximate interplanar d-spacing of 2.04 nm in QTMC-AgNPs. The QTMC-AgNPs exhibited significant antibacterial activity with a clear zone of inhibition of 30 mm and 26 mm around the disks against E. coli and S. aureus, respectively. In addition, QTMC-AgNPs showed highly efficient antifungal activity with 100% and 76.67% growth inhibition against two plant pathogens, S. rolfsii and F. oxysporum, respectively, whereas QTMC revealed no impact. Overall, QTMC-AgNPs showed a promising therapeutic potential and,thus, can be considered for drug design rationale.
This study aims to synthesize and characterize lignin-decorated zinc oxide nanoparticles before incorporating them into resin-modified glass ionomer cement (RMGIC) to improve their anticariogenic potential and mechanical properties (shear bond strength and microhardness). Probe sonication was used to synthesize lignin-decorated zinc oxide nanoparticles which were then characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Following characterization, these were incorporated in RMGIC (Gold label, Fuji II LC). Three major groups, experimental group A (EGA), experimental group B (EGB), and control group (CG), were outlined. EGA and EGB were divided into numbered subgroups based on the ascending concentrations of nanoparticles (5, 10, and 15%) of lignin-coated zinc oxide and zinc-oxide, respectively. CG served as a control and comprised cured RMGIC samples without any incorporation. Anticariogenic analysis was conducted on experimental RMGIC samples via disk-diffusion (n = 3) and direct contact test (n = 3) against Streptococcus mutans (ATCC 25175). Optical density values for days 1, 3, and 5 were recorded via a UV-Vis spectrophotometer. A shear bond strength test was performed using 35 premolars. The adhesive remnant index was used to estimate the site of bond failure. For the Vickers microhardness test (n = 3), 100 g of load at 10 s dwell time was set. Atomic absorption spectroscopy was performed over 28 days to determine the release of zinc from the samples. All tests were analyzed statistically. The anticariogenic potential of EGA and EGB was significantly greater (p ≤ 0.05) than that of the control. The shear bond strength test reported the highest value for EGA15 with all groups exhibiting failure at the bracket/RMGIC interface. The microhardness of EGA15 yielded the highest value (p ≤ 0.05). Release kinetics displayed a steady release with EGB15 exhibiting the highest value. The EGA and EGB samples displayed good anticariogenic potential, which was sustained for 28 days without any deleterious effect on the shear bond strength and microhardness.
Nanocomposites have significantly contributed to biomedical science due to less aggregation behavior and enhanced physicochemical properties. This study synthesized a MnFe2O4@poly(tBGE-alt-PA) nanocomposite for the first time and physicochemically characterized it. The obtained hybrid nanomaterial was tested in vivo for its toxicological properties before use in drug delivery, tissue engineering fields, and environmental applications. The composite was biocompatible with mouse fibroblast cells and hemocompatible with 2% RBC suspension. This nanocomposite was tested on Drosophila melanogaster due to its small size, well-sequenced genome, and low cost of testing. The larvae's crawling speed and direction were measured after feeding. No abnormal path and altered crawling pattern indicated the nonappearance of abnormal neurological disorder in the larva. The gut organ toxicity was further analyzed using DAPI and DCFH-DA dye to examine the structural anomalies. No apoptosis and necrosis were observed in the gut of the fruit fly. Next, adult flies were examined for phenotypic anomalies after their pupal phases emerged. No defects in the phenotypes, including the eye, wings, abdomen, and bristles, were found in our study. Based on these observations, the MnFe2O4@poly(tBGE-alt-PA) composite may be used for various biomedical and environmental applications.
Gold nanoparticles (AuNPs) have undergone significant research for their use in the treatment of cancer. Numerous researchers have established their potent antitumor properties, which have greatly impacted the treatment of cancer. AuNPs have been used in four primary anticancer treatment modalities, namely radiation, photothermal therapy, photodynamic therapy, and chemotherapy. However, the ability of AuNPs to destroy cancer is lacking and can even harm healthy cells without the right direction to transport them to the tumor microenvironment. Consequently, a suitable targeting technique is needed. Based on the distinct features of the human tumor microenvironment, this review discusses four different targeting strategies that target the four key features of the tumor microenvironment, including abnormal vasculature, overexpression of specific receptors, an acidic microenvironment, and a hypoxic microenvironment, to direct surface-functionalized AuNPs to the tumor microenvironment and increase antitumor efficacies. In addition, some current completed or ongoing clinical trials of AuNPs will also be discussed below to further reinforce the concept of using AuNPs in anticancer therapy.
The use of nanometal oxides in nanoagronomy has garnered considerable attention due to their excellent antifungal and plant growth promotion properties. Hybrid nanometal oxides, which combine the strengths of individual nanomaterials, have emerged as a promising class of materials. In this study, nanomagnesium oxide (n-MgO) and hybrid magnetic nanomagnesium oxide (m/n-MgO) were successfully synthesized via the ultrasound-mediated sol-gel method. Characterization results, including TGA, XRD, VSM, and FTIR, confirmed the successful synthesis of m/n-MgO. Both n-MgO and m/n-MgO underwent antifungal assays and plant growth promotion ability studies, benchmarked against the conventional fungicide-copper oxychloride. This study bridges a significant gap by simultaneously reporting the antifungal properties of both n-MgO and m/n-MgO and their impact on plant growth. The disc diffusion assay suggested that the antifungal activity of n-MgO and m/n-MgO against F. oxysporum was inversely related to the particle size. Notably, n-MgO exhibited superior antifungal performance (lower minimum inhibitory concentration (MIC)) and sustained efficacy compared with m/n-MgO, owing to distinct antifungal mechanisms. Nanorod-shaped MgO, with a smaller size (8.24 ± 5.61 nm) and higher aspect ratio, allowed them to penetrate the fungal cell wall and cause intercellular damage. In contrast, cubical m/n-MgO, with a larger size (20.95 ± 9.99 nm) and lower aspect ratio, accumulate on the fungal cell wall surface, disrupting the wall integrity, albeit less effectively against F. oxysporum. Moreover, in plant growth promotion studies, m/n-MgO-treated samples exhibited a 15.7% stronger promotion effect compared to n-MgO at their respective MICs. In addition, both n-MgO and m/n-MgO outperformed copper oxychloride in terms of antifungal and plant growth promoting activities. Thus, m/n-MgO presents a promising alternative to conventional copper-based fungicides, offering dual functionality as a fungicide and plant growth promoter, while the study also delves into the antifungal mechanisms at the intracellular level, enhancing its novelty.
Recently, transdermal monitoring and drug delivery have gained much interest, owing to the introduction of the minimally invasive microneedle (MN) device. The advancement of electroactive MNs electrically assisted in the capture of biomarkers or the triggering of drug release. Recent works have combined conducting polymers (CPs) onto MNs owing to the soft nature of the polymers and their tunable ionic and electronic conductivity. Though CPs are reported to work safely in the body, their biocompatibility in the skin has been insufficiently investigated. Furthermore, during electrical biasing of CPs, they undergo reduction or oxidation, which in practical terms leads to release/exchange of ions, which could pose biological risks. This work investigates the viability and proliferation of skin cells upon exposure to an electrochemically biased MN pair comprising two differently doped poly(3,4-ethylenedioxy-thiophene) (PEDOT) polymers that have been designed for skin sampling use. The impact of biasing on human keratinocytes and dermal fibroblasts was determined at different initial cell seeding densities and incubation periods. Indirect testing was employed, whereby the culture media was first exposed to PEDOTs prior to the addition of this extract to cells. In all conditions, both unbiased and biased PEDOT extracts showed no cytotoxicity, but the viability and proliferation of cells cultured at a low cell seeding density were lower than those of the control after 48 h of incubation.
Photothermal therapy is a promising treatment modality in the realm of cancer therapy. Photothermal nanomaterials that absorb and emit in the near-infrared range (750-900 nm) have drawn a lot of attention recently because of the deep penetration of NIR light in biological tissue. Most nanomaterials, however, are produced by encapsulating or altering the surface of a nanoplatform, which has limited loading capacity and long-term storage. Herein, we developed a stable polymer conjugated with aza-BODIPY that self-assembled to form nanoparticles (aza-BODIPY-mPEG) with better hydrophilicity and biocompatibility while retaining the dye's photothermal conversion characteristics. Aza-BODIPY-mPEG with a hydrodynamic size of around 170 nm exhibited great photostability and excellent photothermal therapy in vitro and in ovo. Aza-BODIPY-mPEG exhibits approximately 30% better anti-angiogenesis and antitumor activity against implanted xenograft human HCT116 tumor in the chick embryo compared to parent aza-BODIPY-A, altogether suggesting that aza-BODIPY-mPEG is a promising material for cancer photothermal therapy.
Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.
Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.
In view of their exceptional approach, excellent inherent biocompatibility and biodegradability properties, and interaction with the local extracellular matrix, protein-based polymers have received attention in bone tissue engineering, which is a multidisciplinary field that repairs and regenerates fractured bones. Bone is a multihierarchical complex structure, and it performs several essential biofunctions, including maintaining mineral balance and structural support and protecting soft organs. Protein-based polymers have gained interest in developing ideal scaffolds as emerging biomaterials for bone fractured healing and regeneration, and it is challenging to design ideal bone substitutes as perfect biomaterials. Several protein-based polymers, including collagen, keratin, gelatin, serum albumin, etc., are potential materials due to their inherent cytocompatibility, controlled biodegradability, high biofunctionalization, and tunable mechanical characteristics. While numerous studies have indicated the encouraging possibilities of proteins in BTE, there are still major challenges concerning their biodegradability, stability in physiological conditions, and continuous release of growth factors and bioactive molecules. Robust scaffolds derived from proteins can be used to replace broken or diseased bone with a biocompatible substitute; proteins, being biopolymers, provide excellent scaffolds for bone tissue engineering. Herein, recent developments in protein polymers for cutting-edge bone tissue engineering are addressed in this review within 3-5 years, with a focus on the significant challenges and future perspectives. The first section discusses the structural fundamentals of bone anatomy and ideal scaffolds, and the second section describes the fabrication techniques of scaffolds. The third section highlights the importance of proteins and their applications in BTE. Hence, the recent development of protein polymers for state-of-the-art bone tissue engineering has been discussed, highlighting the significant challenges and future perspectives.