Recent Advancements in Metallic Au- and Ag-Based Chitosan Nanocomposite Derivatives for Enhanced Anticancer Drug Delivery.

The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise for enhancing the efficacy of cancer therapy through the manufacture of innovative nanocomposite materials. Metallic nanoparticles have been found to enhance the release of anticancer medications that are loaded onto them, resulting in a sustained release, hence reducing the dosage required for drug administration and preventing their buildup in healthy cells. The combination of nanotechnology with biocompatible materials offers new prospects for the development of advanced therapies that exhibit enhanced selectivity, reduced adverse effects, and improved patient outcomes. Chitosan (CS), a polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes for controlled drug delivery due to its biocompatibility and biodegradability. Chitosan nanocomposites exhibit heightened stability, improved biocompatibility, and prolonged release characteristics for anticancer medicines. The incorporation of gold (Au) nanoparticles into the chitosan nanocomposite results in the manifestation of photothermal characteristics, whereas the inclusion of silver (Ag) nanoparticles boosts the antibacterial capabilities of the synthesized nanocomposite. The objective of this review is to investigate the recent progress in the utilization of Ag and Au nanoparticles, or a combination thereof, within a chitosan matrix or its modified derivatives for the purpose of anticancer drug delivery. The research findings for the potential of a chitosan nanocomposite to deliver various anticancer drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, and 6-mercaptopurine, were investigated. Moreover, various modifications carried out on the chitosan matrix phase and the nanocomposite surfaces to enhance targeting selectivity, loading efficiency, and pH sensitivity were highlighted. In addition, challenges and perspectives that could motivate further research related to the applications of chitosan nanocomposites in cancer therapy were summarized.

Advent in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers to accomplish active or homologous tumor targeting for smart amalgamated chemotherapy/photo-therapy: A review.

Conventional cancer mono-therapeutic approaches including radiotherapy, surgery, and chemotherapy don't always achieve satisfactory outcomes and are frequently associated with significant limitations. Although chemotherapy is a vital intervention, its effectiveness is frequently inadequate and is associated with metastasis, multidrug resistance, off-target effect, and normal cells toxicity. Phototherapies are employed in cancer therapy, encompassing photo-dynamic and photo-thermal therapies which under favorable NIR laser light irradiation initiate the included photosensitizers and photo-thermal agents to generate ROS or thermal heat respectively for cancer cells destruction. Photo-therapy is considered noninvasive, posing no resistance, but it still suffers from several pitfalls like low penetration depth and excessive heat generation affecting neighboring tissues. Improved selectivity and tumor-homing capacity could be attained through surface modulation of nanoparticles with targeting ligands that bind to receptors, which are exclusively overexpressed on cancerous cells. Developing novel modified targeted nanoparticulate platforms integrating different therapeutic modalities like photo-therapy and chemotherapy is a topic of active research. This review aimed to highlight recent advances in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers for smart combinatorial chemotherapy/photo-therapy. Nanocarriers decorated with precise targeting ligands, like aptamers, antibody, and lactoferrin, to achieve active tumor-targeting or camouflaging using various biological cell membrane coating are designed to achieve homologous tumor-targeting.

Correction: Novel sensor for the determination of CA 15-3 in serum of breast cancer patients based on Fe-gallic acid complex doped in modified cellulose polymer thin films.

[This corrects the article DOI: 10.1039/D3RA02495D.].

Novel sensor for the determination of CA 15-3 in serum of breast cancer patients based on Fe-gallic acid complex doped in modified cellulose polymer thin films.

Fe-gallic acid MOF embedded in an epoxy methyl cellulose polymer (CMC) thin film was synthesized and characterized by different micro-analytical tools such as: FE-SEM/EDX, XPS analysis, XRD analysis, FT-IR, and fluorescence spectroscopy. Fe-gallic acid MOF doped in a stable CMC polymer thin film is used as a novel sensor to identify CA 15-3 in the sera of patients suffering breast malignancy. The presence of appropriate functional groups in aqueous CA 15-3 solutions enables it to interact with the Fe-gallic acid MOF embedded in the thin film. The Fe-gallic acid MOF was found to absorb energy at 350 nm (λex) and emits radiation at 439 nm which was specifically quenched in the presence of CA 15-3 over a working concentration range of 0.05-570 U mL-1. In contrast to other CA 15-3 detection methods which suffered from electronic noise, interference and slowness, the Fe-gallic acid MOF proved its sensitivity as an economic, stable and reliable probe for the detection and determination of CA 15-3 in patients' serum samples with a detection limit of 0.01 U mL-1 at pH 7.2.

Synthesis and physicochemical properties of an aromatic chitosan derivative: In vitro antibacterial, antioxidant, and anticancer evaluations, and in silico studies.

This study was designed to synthesize a functionalized chitosan by coupling the amine groups of chitosan with 2,4,6-Trimethoxybenzaldehyde, producing a chitosan Schiff base (Cs-TMB). The development of Cs-TMB was verified employing FT-IR, 1H NMR, the electronic spectrum, and elemental analysis. Antioxidant assays exhibited significant ameliorations of Cs-TMB, reporting scavenging activities of 69.67 ± 3.48 % and 39.65 ± 1.98 % for ABTS•+ and DPPH, respectively, while native chitosan showed scavenging ratios of 22.69 ± 1.13 % and 8.24 ± 0.4.1 % toward ABTS•+ and DPPH, respectively. Besides, Cs-TMB exerted significant antibacterial activity up to 90 % with remarkable bactericidal capacity against virulent gram-negative and gram-positive bacteria compared to the original chitosan. Furthermore, Cs-TMB exhibited a safe profile against normal fibroblast cells (HFB4). Interestingly, flow cytometric analysis showed that Cs-TMB demonstrated prominent anticancer properties of 52.35 ± 2.99 % against human skin cancer cells (A375), compared to 10.66 ± 0.55 % for Cs-treated cells. Moreover, Python and PyMOL in-house scripts were used to predict the interaction of Cs-TMB with the adenosine A1 receptor and visualized as a protein-ligand system submerged in a lipid membrane. Overall, these findings accentuate that Cs-TMB could be a favorable representative for wound dressing formulations and skin cancer treatment.

Carbohydrate ligands-directed active tumor targeting of combinatorial chemotherapy/phototherapy-based nanomedicine: A review.

Phototherapies or light mediated therapies, including mutually photothermal and photodynamic therapy that encompass irradiation of the target organs with light, have been widely employed as minimally invasive approach associated with negligible drug resistance for eradicating multiple tumors with minimal hazards to normal organs. Despite all these advantages, many obstacles in phototherapy hinder progress toward clinical application. Therefore, researchers have developed nano-particulate delivery systems integrated with phototherapy and therapeutic cytotoxic drugs to overcome these obstacles and achieve maximum efficacy in cancer treatment. Active targeting ligands were integrated into their surfaces to improve the selectivity and tumor targeting ability, enabling easy binding and recognition by cellular receptors overexpressed on the tumor tissue compared to normal ones. This enhances intratumoral accumulation with minimal toxicity on the adjacent normal cells. Various active targeting ligands, including antibodies, aptamers, peptides, lactoferrin, folic acid and carbohydrates, have been explored for the targeted delivery of chemotherapy/phototherapy-based nanomedicine. Among these ligands, carbohydrates have been applied due to their unique features that ameliorate the bioadhesive, noncovalent conjugation to biological tissues. In this review, the up-to-date techniques of employing carbohydrates active targeting ligands will be highlighted concerning the surface modification of the nanoparticles for ameliorating the targeting ability of the chemo/phototherapy.

Influence of Cedar Essential Oil on Physical and Biological Properties of Hemostatic, Antibacterial, and Antioxidant Polyvinyl Alcohol/Cedar Oil/Kaolin Composite Hydrogels.

Polyvinyl alcohol (PVA) is a safe and biodegradable polymer. Given the unique physical and chemical properties of PVA, we physically cross-linked PVA with kaolin (K) and cedar essential oil (Ced) using the freeze-thawing approach to fabricate PVA/Ced/K sponge hydrogels as hemostatic, antibacterial, and antioxidant wound healing materials. The physicochemical characteristics of PVA/Ced/K hydrogels, including water swelling profiles and gel fractions, were surveyed. Additionally, the functional groups of hydrogels were explored by Fourier transform infrared spectroscopy (FTIR), while their microstructures were studied using scanning electron microscopy (SEM). Furthermore, the thermal features of the hydrogels were probed by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Evidently, alterations in cedar concentrations resulted in significant variations in size, water uptake profiles, and hydrolytic degradation of the hydrogels. The incorporation of cedar into the PVA/K endowed the hydrogels with significantly improved antibacterial competency against Bacillus cereus (B. cereus) and Escherichia coli (E. coli). Moreover, PVA/Ced/K exhibited high scavenging capacities toward ABTS•+ and DPPH free radicals. Beyond that, PVA/Ced/K hydrogels demonstrated hemocompatibility and fast blood clotting performance in addition to biocompatibility toward fibroblasts. These findings accentuate the prospective implementation of PVA/Ced/K composite hydrogel as a wound dressing.

Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin.

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.

Enhancement of wound healing by chitosan/hyaluronan polyelectrolyte membrane loaded with glutathione: in vitro and in vivo evaluations.

The inflammation of chronic wounds generally causes delaying their healing process. The present work aims to formulate a wound dressing polyelectrolyte membrane based on chitosan (Ch) and sodium hyaluronate (HA) loaded with glutathione (GSH). The membrane types (Ch/HA and Ch/HA/GSH) were examined by Fourier transform infrared spectroscopy (FT-IR). The material properties were further investigated using thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). Physical characteristics of the prepared membranes, such as wettability, surface roughness, and mechanical properties were determined by standard experimental methods. In vitro assays were used to evaluate the haemocompatibility, thrombogenicity, and cytotoxicity of the membranes. The wound healing examined using a standard rat model exhibited a progress at exploiting the Ch/HA/GSH-type membranes compared to a bicomponent Ch/HA membrane or a "dry" healing wound. Histological examination of the recovered skin confirmed the visual observations. In conclusion, in vivo study results assert that Ch/HA/GSH is a proper wound-dressing for healing the chronic skin wounds.

Chitosan/hyaluronan/edaravone membranes for anti-inflammatory wound dressing: In vitro and in vivo evaluation studies.

A novel wound healing material composed of chitosan (Ch) and hyaluronan (HA) boosted with edaravone (Ed) as an anti-inflammatory drug was developed. The fabricated membranes were verified using FT-IR, and the thermal properties were estimated employing TGA instrument. Moreover, Physical characterizations of the prepared membranes demonstrated a decrease in the membrane wettability, whereas an increase in membrane roughness was monitored due to the effect of edaravone supplementation. A comparative study of free-radical scavenging activity of edaravone itself was carried out by two in vitro approaches: uninhibited/inhibited hyaluronan degradation and decolorization of ABTS methods in normal and simulated inflammation condition (acidic condition). Accordingly, the scavenging activity of edaravone was significantly diminished to OH and peroxy-/alkoxy-type radicals in acidic conditions in compared to the neutral reactions. The biochemical studies evidenced the haemocompatibility of the examined membranes. The consequence of membranes composed of Ch/HA/Ed on the wound healing of the rat's skin was studied, and the macroscopic and microscopic investigations revealed remarkable healing at 21st day post-surgery compared with injuries treated with cotton gauze as a negative control in addition to Ch/HA membrane without edaravone. For these reasons, the Ch/HA/Ed membrane could be implemented as wound dressing material.

Enzyme-catalyzed modification of PES surfaces: reduction in adsorption of BSA, dextrin and tannin.

Poly(ethersulfone) (PES) can be modified in a flexible manner using mild, environmentally benign components such as 4-hydroxybenzoic acid and gallic acid, which can be attached to the surface via catalysis by the enzyme laccase. This leads to grafting of mostly linear polymeric chains (for 4-hydroxybenzoic acid, and for gallic acid at low concentration and short modification time) and of networks (for gallic acid at high concentration and long exposure time). The reaction is stopped at a specific time, and the modified surfaces are tested for adsorption of BSA, dextrin and tannin using in-situ reflectometry and AFM imaging. At short modification times, the adsorption of BSA, dextrin and tannin is significantly reduced. However, at longer modification times, the adsorption increases again for both substrates. As the contact angle on modified surfaces at short modification times is reduced (indicative of more hydrophilic surfaces), and keeps the same low values at longer modification times, hydrophilicity is not the only determining factor for the measured differences. At longer modification times, intra-layer reactivity will increase the amount of cross-linking (especially for gallic acid), branching (for 4-hydroxybenzoic acid) and/or collapse of the polymer chains. This leads to more compact layers, which leads to increased protein adsorption. The modifications were shown to have clear potential for reduction of fouling by proteins, polysaccharides, and polyphenols, which could be related to the surface morphology.