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Nanoparticle (NP) functionalization with specific ligands enhances targeted cancer therapy and imaging by promoting receptor recognition and improving cellular uptake. This review focuses on recent research exploring the interaction between cancer cell-expressed chemokine receptor 4 (CXCR4) and ligand-conjugated NPs, utilising small molecules, peptides, and antibodies. Active NP targeting has shown improved tumour targeting and reduced toxicity, enabling precision therapy and diagnosis. However, challenges persist in the clinical translation of targeted NPs due to issues with biological response, tumour accumulation, and maintaining NP quality at an industrial scale. Biological and intratumoral barriers further hinder efficient NP accumulation in tumours, hampering translatability. To address these challenges, the academic community is refocusing efforts on understanding NP biological fate and establishing robust preclinical models. Future studies should investigate NP-body interactions, develop computational models, and identify optimal preclinical models. Establishing central NP research databases and fostering collaboration across disciplines is crucial to expediting clinical translation. Overcoming these hurdles will unlock the transformative potential of CXCR4-ligand-NP conjugates in revolutionising cancer treatment.

Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa . It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability. This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained. The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD. In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.

A response surface methodology based on the Box-Behnken design was employed to develop fucoxanthin (FX) delivery nanocarrier from alginate (ALG) and chitosan (CS). The FX-loaded ALG/CS nanoparticles (FX-ALG/CS-NPs) were fabricated using oil-in-water emulsification and ionic gelation. The optimal formulation consisted of an ALG:CS mass ratio of 0.015:1, 0.71 % w/v Tween™ 80, and 5 mg/mL FX concentrations. The resulting FX-ALG/CS-NPs had a size of 227 ± 23 nm, a zeta potential of 35.3 ± 1.7 mV, and an encapsulation efficiency of 81.2 ± 2.8 %. These nanoparticles exhibited enhanced stability under simulated environmental conditions and controlled FX release in simulated gastrointestinal fluids. Furthermore, FX-ALG/CS-NPs showed increased in vitro oral bioaccessibility, gastrointestinal stability, antioxidant activity, anti-inflammatory effect, and cytotoxicity against various cancer cells. The findings suggest that ALG/CS-NPs are effective nanocarriers for the delivery of FX in nutraceuticals, functional foods, and pharmaceuticals., Competing Interests: Declaration of competing interest The authors assert that there are no competing financial interests or personal relationships that could have influenced the work reported in this paper. Furthermore, all authors confirm the absence of any conflicts of interest amongst themselves., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Magnetic drug targeting can be a strategy for effectively delivering phytochemicals in cancer treatment. Here, we demonstrate the benefit of magnetic targeting with superparamagnetic iron oxide nanoparticles for cytotoxicity enhancement of lutein (LUT) against breast cancer cells. Fabrication of LUT-loaded chitosan/alginate iron oxide nanoparticles (LUT-CS/Alg-Fe 3 O 4 -NPs) was optimized by a statistical approach using response surface methodology based on the Box-Behnken design. The optimized LUT-CS/Alg-Fe 3 O 4 -NPs with a balance among LUT concentration, copolymer coating, and iron ion concentration exhibited controlled size, narrow size distribution, better crystallinity, excellent saturation magnetization, and sustained-release profile. The negligible magnetic coercivity and remanent magnetization confirmed the superparamagnetism of the prepared NPs. The optimized LUT-CS/Alg-Fe 3 O 4 -NPs were biocompatible while exhibiting a significantly enhanced cytotoxicity towards breast cancer MCF-7 cells upon exposure to a permanent magnet compared to free LUT with a 4-fold increase, suggesting the potential of LUT-CS/Alg-Fe 3 O 4 -NPs as magnetically targeted delivery for breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nanotechnology plays an integral role in multimodal analgesia. In this study, we co-encapsulated metformin (Met) and curcumin (Cur) into chitosan/alginate (CTS/ALG) nanoparticles (NPs) at their synergistic drug ratio by applying response surface methodology. The optimized Met-Cur-CTS/ALG-NPs were achieved with Pluronic® F-127 2.33 % (w/v), Met 5.91 mg, and CTS:ALG mass ratio 0.05:1. The prepared Met-Cur-CTS/ALG-NPs had 243 nm particle size, -21.6 mV zeta potential, 32.6 and 44.2 % Met and Cur encapsulations, 19.6 and 6.8 % Met and Cur loading, respectively, and 2.9:1 Met:Cur mass ratio. Met-Cur-CTS/ALG-NPs displayed stability under simulated gastrointestinal (GI) fluid conditions and during storage. In vitro release study of Met-Cur-CTS/ALG-NPs in simulated GI fluids showed sustained release, with Met exhibiting Fickian diffusion and Cur demonstrating non-Fickian diffusion following the Korsmeyer-Peppas model. Met-Cur-CTS/ALG-NPs exhibited increased mucoadhesion and improved cellular uptake in Caco-2 cells. Additionally, Met-Cur-CTS/ALG-NPs exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophage and BV-2 microglial cells than the equivalent amount of the Met-Cur physical mixture, indicating a greater ability to modulate peripheral and central immune mechanisms of pain. In the mouse formalin-induced pain model, Met-Cur-CTS/ALG-NPs administered orally exhibited better attenuation of pain-like behaviors and proinflammatory cytokine release compared to the Met-Cur physical mixture. Furthermore, Met-Cur-CTS/ALG-NPs did not induce significant side effects in mice at therapeutic doses. Altogether, the present study establishes a CTS/ALG nano-delivery system for Met-Cur combination against pain with improved efficacy and safety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Curcumin diethyl disuccinate (CDD) is an ester prodrug of curcumin that has better chemical stability in phosphate buffer (pH 7.4) and anticancer activities against MDA-MB-231 human breast cancer cells and Caco-2 cells than curcumin. However, a major drawback of CDD is its poor water solubility and low bioavailability in the gastrointestinal tract. To overcome these problems, a nanoformulation was developed using chitosan/alginate nanoparticles (CANPs) under the optimal condition as previously derived by statistical optimization. The CDD-loaded CANPs (CDD-CANPs) were found to exhibit good stability after exposure to simulated digestive fluids and ultraviolet light, and a sustained-release profile of CDD in the simulated digestive and body fluids. The in vitro release pattern fitted well to the Peppas-Sahlin model, indicating that the release of CDD was mainly governed by diffusion. Compared to free CDD, the CDD-CANPs showed better stability, bioaccessibility, bioavailability, cellular uptake, and cytotoxicity against HepG2 cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chitosan/alginate nanoparticles (CANPs) were formulated to encapsulate curcumin diethyl diglutarate (CDG) for oral delivery. CDG-loaded CANPs (CDG-CANPs) were prepared by o/w emulsification and ionotropic gelation. The optimization of CDG-CANPs was successfully performed by response surface methodology. The characteristics including photostability, storage stability, digestive stability, in vitro digestibility, bioaccessibility and in vitro uptake in Caco-2 cells of free CDG and CDG-CANPs were investigated. The optimal CDG-CANPs could be prepared by chitosan/alginate mass ratio of 0.065:1, 1% (w/v) Pluronic®F127 and 4.5 mg/mL of CDG. The optimized nanoparticles had the particle size, zeta potential, encapsulation efficiency and loading capacity of 215 nm, -24.1 mV, 85% and 27%, respectively. The CDG-CANPs showed better stability under UV irradiation and thermal exposure compared with free CDG. The CDG-CANPs had stability up to 3 months at 4 °C. The in vitro release profile showed sustained-release manner and best fit with the Korsmeyer-Peppas kinetic model, indicating the Fickian diffusion mechanism. Nanoparticle encapsulation significantly enhanced in vitro digestibility and bioaccessibility under simulated gastrointestinal conditions and cellular uptake of CDG. The overall results suggest that CANPs are promising candidates for encapsulation, protection and controlled release of CDG, a hydrophobic compound, with an improvement of physicochemical stabilities, digestibility, bioaccessibility and cellular uptake., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment of inflammatory skin diseases. In this study, we demonstrate that a combination of curcumin-loaded chitosan/alginate nanoparticles (Cur-CS/Alg NPs) and blue light emitting diodes (LED) light irradiation effectively suppressed the hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced cultured human kerlatinocyte (HaCaT) cells. The Cur-CS/Alg NPs were fabricated by emulsification of curcumin in aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan using an optimized formulation derived from a Box-Behnken design. The fabricated Cur-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The surrogate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, to measure the relative number of viable cells, showed that the CS/Alg NPs were nontoxic to normal HaCaT cells, while 0.05 µg/mL and 0.1 µg/mL of free curcumin and Cur-CS/Alg NPs inhibited the hyperproliferation of HaCaT cells induced by TNF-α. However, the Cur-CS/Alg NPs demonstrated a stronger effect than the free curcumin, especially when combined with blue light irradiation (10 J/cm²) from an LED-based illumination device. Therefore, the Cur-CS/Alg NPs with blue LED light could be potentially developed into an effective PDT system for the treatment of psoriasis.

Curcumin diglutaric acid (CG) is a prodrug of curcumin that shows better solubility and antinociceptive activity compared to curcumin. To improve its properties further, CG was encapsulated into polysaccharide-based nanoparticles in this study. A chitosan/alginate nanoparticulate system was chosen for encapsulation of CG due to its biocompatibility, biodegradability, non-toxicity, mucoadhisiveness and good film formation. CG-loaded chitosan/alginate nanoparticles were prepared by o/w emulsification and ionotropic gelification, with the conditions optimized using response surface methodology. A chitosan/alginate mass ratio of 0.04:1, CG concentration of 3 mg/mL and Pluronic®F127 concentration of 0.50% (w/v) were determined to be optimal for the nanoparticle preparation. FTIR and XRD confirmed encapsulation of CG into the chitosan/alginate nanoparticles. The CG-loaded chitosan/alginate nanoparticles showed better stability under UV radiation and in a simulated gastrointestinal environment, compared to a CG dispersion in water. The nanoparticles showed slow cumulative release of CG in simulated gastrointestinal fluids without enzymes and in body fluid. A Weibull model of the best fit for all conditions suggested that the release pattern of CG from CG-loaded chitosan/alginate nanoparticles was mainly controlled by Fickian diffusion and erosion of polymer materials. Finally, CG-loaded chitosan/alginate nanoparticles showed higher in vitro cellular uptake in human epithelial colorectal adenocarcinoma (Caco-2 cells) and better anticancer activity against Caco-2, human hepatocellular carcinoma (HepG2) and human breast cancer (MDA-MB-231) cells. Therefore, the CG-loaded chitosan/alginate nanoparticles are a promising approach for oral administration of CG for cancer treatment., (Copyright © 2018. Published by Elsevier B.V.)

The unique characteristics of enveloped viruses including nanometer size, consistent morphology, narrow size distribution, versatile functionality and biocompatibility have attracted attention from scientists to develop enveloped viruses for biomedical applications. The biomedical applications of the viral-based nanoparticles include vaccine development, imaging and targeted drug delivery. The modification of the structural elements of enveloped viruses is necessary for the desired functions. Here, we review the chemical approaches that have been utilized to develop bionanomaterials based on enveloped viruses for biomedical applications. We first provide an overview of the structures of enveloped viruses which are composed of nucleic acids, structural and functional proteins, glycan residues and lipid envelope. The methods for modification, including direct conjugation, metabolic incorporation of functional groups and peptide tag insertion, are described based on the biomolecular types of viral components. Layer-by-layer technology is also included in this review to illustrate the non-covalent modification of enveloped viruses. Then, we further elaborate the applications of chemically-modified enveloped viruses, virus-like particles and viral subcomponents in biomedical research.

• Conjugating the beta-thiopropanamide linker promoted selective cytotoxicity. • The conjugate containing the linker could self-assemble into large nanoparticles. • The conjugate containing the linker could impart cancer enzyme-responsiveness. • The PEGylation of doxorubicin provided sustained drug release and improved stability. Doxorubicin (DOX) is a chemotherapeutic agent that suffers from severe adverse effects due to non-selective cell cytotoxicity. This study designs a novel beta -thiopropanamide linker (A) which conjugates DOX with methoxypolyethylene glycol (mPEG) to sustain systemic drug release, and to promote cancer enzyme-responsiveness and cell selectivity. The mPEG-DOX conjugate with the beta-thiopropanamide linker (P-A-DOX) conjugate was synthesized using thiol-functionalized methoxypolyethylene glycol and acrylic acid to establish the beta -thiopropanamide linkage with DOX, with the mPEG-DOX (P-DOX) conjugate as the control. The conjugates were structurally characterized by NMR, chemical assay, transmission electron microscopy and dynamic light scattering technique. The in vitro hydrolytic stability as a function of pH and cytotoxicity tests (MDA-MB-231 and MCF-7 breast cancer cells vs MCF-10A noncancerous cells) were performed. The P-A-DOX and P-DOX conjugates can self-assemble into nanoparticles. The P-A-DOX and P-DOX conjugates exhibited sustained drug release and improved physicochemical stability under physiological pHs. Their cancer cell cytotoxicity and selectivity progressed in the following order: P-A-DOX > P-DOX > DOX. The P-A-DOX conjugate with the beta -thiopropanamide linker is a selective DOX nanodelivery system for breast cancer treatment. [ABSTRACT FROM AUTHOR]