Carrier For Doxorubicin Research Articles

Bone marrow mesenchymal stem cell-derived exosomes improve cancer drug delivery in human cell lines and a mouse osteosarcoma model.

Osteosarcoma is the most common primary bone tumor. Patients require chemotherapy drugs with high-targeting ability and low off-target toxicity to improve their survival. Exosomes are biological vesicles that mediate long-distance communication between cells and naturally target their source sites. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) naturally target bone tumor sites, suggesting their potential as effective anti-tumor therapy vectors. In this study, we evaluated the potential of BMSC-derived exosomes in targeting osteosarcoma and serving as a carrier for doxorubicin (DOX). We isolated exosomes from human BMSCs and synthesized hybrid exosomes (HEs) by fusing these exosomes with liposomes. These HEs were loaded with DOX to produce a novel drug, HE/DOX. We confirmed the successful synthesis of HE/DOX using fluorescence spectroscopy and estimated its size to be 151.1 ± 10.2 nm. HEs expressed the known exosomal proteins ALIX, CD63, and TSG101. Under acidic conditions similar to those observed in the tumor microenvironment, the drug release from HE/DOX was enhanced. In osteosarcoma cell lines and in a mouse osteosarcoma model, HE/DOX exhibited stronger tumor-inhibitory effects than free DOX. Our study demonstrates that BMSC-derived exosomes could effectively target osteosarcoma. Furthermore, HEs can serve as effective carriers of DOX, enabling the treatment of osteosarcoma. These findings highlight a promising direction for tumor-targeted therapy.

Synthesis and self-assembly of perylene-cored poly(amidoamine) dendrimers with poly[2-(dimethylamino)ethyl methacrylate]-modified arms as fluorescent bio-imaging probes and doxorubicin carriers

A poly(amidoamine) (PAMAM) dendrimer is prepared using a divergent method, with perylene-3,4,9,10-tetracarboxylic diimide (PTCDI) as luminescent core. The peripheral amines are modified using α-bromoisobutyryl bromide, allowing the dendrimers to act as macroinitiators for the synthesis of poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) through atom transfer radical polymerization (ATRP) with three different degrees of polymerization. The successful synthesis is verified by conducting a range of analyses, including Fourier-transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and X-ray diffraction (XRD). Additionally, the impact of changes in solution pH on the self-assembly of dendrimers is explored. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) showed unique morphologies, including spherical micelles and cubic-hexagonal structures, at varying pH levels. The self-assembled dendrimers are utilized to load doxorubicin (DOX) and the drug release kinetics are studied under various conditions. The biocompatibility of the dendrimers is assessed using the MTT assay against SH-SY5Y cells. Additionally, higher dendrimer generations improved the solubility, compatibility, and fluorescent properties of the core. The dendrimers' capacity for cellular uptake and fluorescence imaging is also evaluated using SH-SY5Y cells, demonstrating their effectiveness in live-cell fluorescence imaging.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Targeted redox-responsive peptide for arterial chemoembolization therapy of orthotropic hepatocellular carcinoma

ObjectiveTranscatheter Arterial Chemoembolization (TACE) is the first choice for the treatment of advanced-stage hepatocellular carcinoma (HCC). However, TACE suffers from a lack of specificity and rapid drug release. Herein, a targeted redox-responsive peptide (TRRP) was synthesized and used as a carrier of doxorubicin (DOX) to enhance the efficacy of TACE through tumor cells targeting and controlled drug release.MethodsTRRP has a high loading capacity of DOX and a sensitive drug release behavior at high glutathione (GSH) concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models.ResultsTRRP has a high loading capacity of DOX and a sensitive drug release behavior at GSH concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models.ConclusionsThis study demonstrated that TRRP was a promising therapeutic agent for enhancing TACE therapy for HCC treatment.Graphical abstract

Insights into Transfer of Supramolecular Doxorubicin/Congo Red Aggregates through Phospholipid Membranes.

Doxorubicin (DOX) is a commonly used chemotherapeutic drug, from the anthracycline class, which is genotoxic to neoplastic cells via a DNA intercalation mechanism. It is effective and universal; however, it also causes numerous side effects. The most serious of them are cardiotoxicity and a decrease in the number of myeloid cells. For this reason, targeted DOX delivery systems are desirable, since they would allow lowering the drug dose and therefore limiting systemic side effects. Recently, synthetic dyes, in particular Congo red (CR), have been proposed as possible DOX carriers. CR is a planar molecule, built of a central biphenyl moiety and two substituted naphthalene rings, connected with diazo bonds. In water, it forms elongated ribbon-shaped supramolecular structures, which are able to selectively interact with immune complexes. In our previous studies, we have shown that CR aggregates can intercalate DOX molecules. In this way, they preclude DOX precipitation in water solutions and increase its uptake by MCF7 breast cancer cells. In the present work, we further explore the interactions between DOX, CR, and their aggregates (CR/DOX) with phospholipid membranes. In addition to neutral molecules, the protonated doxorubicin form, DXP, is also studied. Molecular dynamics simulations are employed to study the transfer of CR, DOX, DXP, and their aggregates through POPC bilayers. Interactions of CR, DOX, and CR/DOX with model monolayers are studied with Langmuir trough measurements. This study shows that CR may support the transfer of doxorubicin molecules into the bilayer. Both electrostatic and van der Waals interactions with lipids are important in this respect. The former promote the initial stages of the insertion process, the latter keep guest molecules inside the bilayer.

Role of mesoporous silica functionalized with boronic acid derivative in targeted delivery of doxorubicin and co-delivery of doxorubicin and resveratrol

Phenylboronic acid derivatives have gained interest due to their ability to reversibly bind to 1,2-diols, such as sialic acid receptors overexpressed by breast cancer cells. In this study, two types of mesoporous silica, MCM-41 and SBA-15, were functionalized with 4-carboxyphenylboronic acid (CPBA) through the amidation reaction, and the resulting materials MCM-CPBA and SBA-CPBA were used as carriers for doxorubicin (Dox) or for co-delivery of doxorubicin and resveratrol. In the case of MCM-CPBA material, all amine groups were involved in the condensation reaction with boronic acid derivative, while in the case of SBA-CPBA, free amine groups remained on the silica surface. Dox release profiles, performed in phosphate buffer solution pH 5.5, showed a faster release kinetics of Dox and a higher cumulative drug release for co-delivery system. Larger pores of SBA-15-type carrier influenced the Dox release profile as the diffusion of drug molecules was favored, a higher cumulative drug release being obtained in the case of SBA-CPBA than for MCM-CPBA. Biological assessment of the developed drug delivery systems demonstrated lower cytotoxicity on BJ fibroblasts than on BT474 breast cancer cells. Evaluation of drug delivery systems by hyperspectral microscopy evidenced a higher internalization rate of Dox when was loaded on functionalized silica carriers compared to the free drug into BT474 cells. The internalization rate of doxorubicin-loaded carrier depended on the type of carrier; a better internalization was observed for cancer cells when were treated with Dox-loaded MCM-CPBA nanoparticles than for Dox-loaded SBA-CPBA that might be attributed to smaller size of MCM-CPBA nanoparticles.

Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

Porphyrin-based covalent organic frameworks as doxorubicin delivery system for chemo-photodynamic synergistic therapy of tumors

Photodynamic therapy (PDT) is a non-invasive treatment method that has garnered significant attention in recent years. Nanoparticle-based drug delivery systems can achieve targeted drug release, thereby significantly reducing side effects and enhancing therapeutic efficacy. In this study, a covalent organic framework (COF) with an approximately spherical structure connected by azo bonds was synthesized. The synthesized COF was utilized as a hypoxia-responsive carrier for doxorubicin (DOX) drug delivery and was modified with hyaluronic acid (HA). DOX@COF@HA exhibited a reactive release under hypoxic conditions. Under normal oxygen conditions, the release of DOX was 16.9 %, increasing to 60.2 % with the addition of sodium hydrosulfite. In vitro experiments revealed that the group combining photodynamic therapy with chemotherapy exhibited the lowest survival rates for 4T1 and MHCC97-L cells. In vivo experiments further validated the effectiveness of combination therapy, resulting in a tumor volume of only 33 mm3 after treatment, with no significant change in mouse weight during the treatment period. DOX@COF@HA nanoplatforms exhibit substantial potential in tumor treatment.

DNA tetrahedron as a carrier of doxorubicin for metastatic breast cancer treatment

AbstractMetastatic breast cancer is a significant clinical challenge calling for novel and efficient therapeutic approaches. DNA tetrahedron, a highly programmable nanocage, offers some promising attributes including biocompatibility, stability, and functionalization making it an attractive candidate for drug delivery. In this study, we have explored the potential of DNA tetrahedron as a carrier of doxorubicin, a DNA and RNA synthesis‐inhibiting chemotherapy drug. We have encapsulated doxorubicin in DNA tetrahedron (TD : Dox) and subsequently focused on metastatic breast cancer cells for the effect of the same. We showed that TD : Dox has the potential to inhibit the migration of cancerous cells in the 2D model and inhibit the invasion of tumor cells in the 3D model as well. This system also can be uptaken in in vivo zebrafish model as well. Overall, this study promises the TD : Dox system as an ideal drug delivery model and a viable approach for metastatic breast cancer treatment.

Fabrication and characterization of 3D-printed composite scaffolds of coral-derived hydroxyapatite nanoparticles/polycaprolactone/gelatin carrying doxorubicin for bone tissue engineering

In this study, nanocomposite scaffolds of hydroxyapatite (HA)/polycaprolactone (PCL)/gelatin (Gel) with varying amounts of HA (42–52 wt. %), PCL (42–52 wt. %), and Gel (6 wt. %) were 3D printed. Subsequently, a scaffold with optimal mechanical properties was utilized as a carrier for doxorubicin (DOX) in the treatment of bone cancer. For this purpose, HA nanoparticles were first synthesized by the hydrothermal conversion of Acropora coral and characterized by using different techniques. Also, a compression test was performed to investigate the mechanical properties of the fabricated scaffolds. The mineralization of the optimal scaffold was determined by immersing it in simulated body fluid (SBF) solution for 28 days, and the biocompatibility was investigated by seeding MG-63 osteoblast-like cells on it after 1–7 days. The obtained results showed that the average size of the synthesized HA particles was about 80 nm. The compressive modulus and strength of the scaffold with 47 wt. % HA was reported to be 0.29 GPa and 9.9 MPa, respectively, which was in the range of trabecular bones. In addition, the scaffold surface was entirely coated with an apatite layer after 28 days of soaking in SBF. Also, the efficiency and loading percentage of DOX were obtained as 30.8 and 1.6%, respectively. The drug release behavior was stable for 14 days. Cytotoxicity and adhesion evaluations showed that the fabricated scaffold had no negative effects on the viability of MG-63 cells and led to their proliferation during the investigated period. From these results, it can be concluded that the HA/PCL/Gel scaffold prepared in this study, in addition to its drug release capability, has good bioactivity, mechanical properties, and biocompatibility, and can be considered a suitable option for bone tumor treatment.Graphical

Carbon nanomaterials as carriers for the anti-cancer drug doxorubicin: a review on theoretical and experimental studies.

The incidence of cancer is increasing worldwide in a life-threatening manner. In such a scenario, the development of anti-cancer drugs with minimal side effects and effective drug delivery systems is of paramount importance. Doxorubicin (DOX) is one of the powerful anti-cancer drugs from the chemical family anthracycline, which is used to treat a wide variety of cancers, including breast, prostate, ovarian, and hematological malignancies. However, DOX has been associated with many side effects, including lethal cardiotoxicity, baldness, gastrointestinal disturbances and cognitive function impairment. Even though DOX is administered in liposomal formulations to reduce its toxicity and enhance its therapeutic profile, the liposomal formulations themselves have certain therapeutic profile limitations such as "palmar-plantar erythrodysesthesia (PPE)", which shows severe swelling and redness in the skin, thus restricting the dosage and reducing patient compliance. In contemporary chemotherapy research, there is a great interest in the utilization of nanomaterials for precise and targeted drug delivery applications, especially using carbon-based nanomaterials. This review provides a comprehensive overview of both experimental and theoretical scientific works, exploring diverse forms of carbon-based materials such as graphene, graphene oxide, and carbon nanotubes that function as carriers for DOX. In addition, the review consolidates information on the fate of the carriers after the delivery of the payload at the site of action through different imaging techniques and the various pathways through which the body eliminates these nanomaterials. In conclusion, the review presents a detailed overview of the toxicities associated with these carriers within the human body, contributing to the development of enhanced drug delivery systems.

Revolutionizing Healthcare through Applications and Challenges of Nanomaterials in Targeted Drug Delivery and Therapeutics

This research investigates the cutting edge of healthcare advancement through the applications and challenges of nanomaterials focused on sedate conveyance and therapeutics. Gold nanoparticles (AuNPs) and liposomes were synthesized, characterized, and utilized as carriers for doxorubicin, illustrating remarkable medicate stacking capacities of 4.5% and 80.2%, individually. The discharge energy uncovered a Higuchi demonstration for AuNPs and first-order energy for liposomes, exhibiting custom-fitted medicate discharge profiles. In vitro studies illustrated critical cytotoxicity, with an IC50 of 12.3 µM for AuNPs in A549 cells and 8.7 µM for liposomes in MCF-7 cells. Cellular take-up rates of 35.6% and 50.2% advance asserted their adequacy. Moving to in vivo studies, the circulation half-life of AuNPs was 6.2 hours, whereas liposomes displayed a longer half-life of 8.5 hours. Bio distribution ponders illustrated particular aggregation within the tumor, coming to 4.8% ID/g for AuNPs and 6.2% ID/g for liposomes. Helpful results included tumor measure decrease and by and large survival rates of 75.4% for AuNPs and 82.7% for liposomes. Comparison with related works highlighted the competitive execution of the created nanomaterials, emphasizing their potential in progressing exactness medication. This research contributes to the advancing scene of nanomedicine, emphasizing personalized and maintainable healthcare arrangements.

Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy.

A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

Magnetic Iron Oxide Nanoparticles Coated with Polyethylene and Gold as a Suitable Carrier for Doxorubicin and its Effect on Mcf-7 Breast Cancer Cells

Introduction: Nanotechnology always seeks to provide new solutions for targeted delivery of chemotherapy drugs, in order to increase the quality of cancer treatment and reduce the side effects of chemotherapy. The aim of this study was to load the anticancer drug doxorubicin on Magnetic iron oxide nanoparticles were subjected to physico-chemical evaluation for their effect on MCF-7 cells.
 Methods: This research was a descriptive-analytical study. In this laboratory research, iron oxide nanoparticles were first synthesized by precipitation method. Then they were coated with polyethylene imine and gold. After loading the drug doxorubicin into the magnetic iron oxide nanoparticles, the physiochemical parameters of the nanosystem from the point of view of insertion efficiency, drug release profile under similar conditions of healthy and cancer cells, size, zeta potential and morphology were determined.
 Results: The magnetic nanocarriers had a diameter of 90 nm and a zeta potential of 66.7 mV. The maximum release of the drug from the nanosystem at 37°C, pH=7.4 and 42°C, pH=5.4 and after 48 hourswas 48% and 66%, respectively. The SEM analysis showed the spherical morphology and the absence of chemical interaction between the nanosystem and the drug. The investigation of the performance of the nanosystem indicated an increase in the toxicity of encapsulated doxorubicin compared to free doxorubicin at similar concentrations on the MCF_7 strain.
 Conclusion: The results of this research showed that the magnetic iron oxide nanoparticle system, while having appropriate physiochemical characteristics, does not change the chemical nature of the drug and can be a suitable and semi-targeted carrier for the anticancer drug doxorubicin.

Study on the gelation and sustained release effect of the thermosensitive material TPGS1000

AbstractPolyethylene glycol 1000 vitamin E succinate (TPSG1000) was commonly used as absorption promoter, solubilizer, and emulsifier in drug delivery systems. In addition, TPGS1000 possessed thermosensitivity and gelling property that were not extensively studied. Hence, TPGS1000 was synthesized by Collnot method, characterized, evaluated for gelling property, and applied as the thermosensitive carrier in the study. Thin‐layer chromatography, Fourier transform infrared spectroscopy, and high‐performance liquid chromatography methods proved that the TPGS1000 was successfully synthesized. Under the condition of 4.5% sodium sulfate, 12% TPGS1000 could rapidly form stable hydrogels at 37°C. In addition, the gelling time tends to shorten with temperature increasing. It is worth noting that TPGS1000 as the carrier for loading doxorubicin displayed significant sustained release behavior. In conclusion, the study laid foundation for the application and further research of TPGS1000 in thermosensitive gel drug delivery system and provides a novel material for thermosensitive gel preparations.

Terpyridine Functionalized Cyclodextrin Nanoparticles as Carriers for Doxorubicin: Analysis of In Vitro Antiproliferative Activity.

We have recently described the development of cyclodextrin-based nanoparticles (NPs) functionalized with terpyridine and decorated with biotin-terpyridine ligands via Cu(II) and Fe(II) coordination. In the present study, we report the performance of these novel NPs as a delivery system for anticancer drugs. In particular, we analyzed the feasibility of loading these new NPs with the topoisomerase II inhibitor Doxorubicin (Doxo), still administered to patients to treat different forms of cancers. We developed Doxo-encapsulated polymeric NPS to generate nanoformulations with higher efficacy than free Doxo. We investigated the inhibition of cell proliferation in A2780, A549, SKHep1, and MDA-MB-453 cancer cell lines using the MTT assay. NPs loaded with Doxo displayed higher antiproliferative activity than free Doxo. The NPs generated in this study inhibited the proliferation of cancer cells and were able to entrap the classic anticancer drug Doxo. The Doxo-loaded NP showed increased cytotoxicity in comparison to free Doxo.

Enhancing the drug delivery efficacy of nanodiamond (C20H22): A DFT-based study of doxorubicin and melphalan interaction on pristine and doped surfaces

In this study, density functional theory calculations were conducted to investigate the interaction and electronic properties of two anti-cancer drugs, doxorubicin and melphalan, using pristine and Cr-doped nanodiamonds. The interaction energies of doxorubicin and melphalan onto pristine nanodiamond were calculated to be −259.584 kJ/mol and −251.286 kJ/mol, respectively, indicating an exothermic process. Doping the nanodiamond with Cr enhanced the interaction, with energies of −297.786 kJ/mol for doxorubicin and −286.694 kJ/mol for melphalan. Chemical hardness, highest occupied molecular orbital, and lowest unoccupied molecular orbital analysis showed that both doped complexes with Cr were relatively soft, with nanodiamond-doxorubicin being softer than nanodiamond-melphalan. The high dipole moment of doped nanodiamond-Cr-doxorubicin 9.979 Debye compared to nanodiamond-doxorubicin 3.989 Debye suggests that doped nanodiamond-doxorubicin is more interaction. Thermodynamic calculations revealed the spontaneity and stability of these complexes. Overall, the results demonstrate the enhanced drug loading capacity of Cr-doped nanodiamonds and their potential as drug delivery carriers for doxorubicin and melphalan.

Mucoadhesive Mesoporous Silica Particles as Versatile Carriers for Doxorubicin Delivery in Cancer Therapy.

Due to their structural, morphological, and behavioral characteristics (e.g., large volume and adjustable pore size, wide functionalization possibilities, excellent biocompatibility, stability, and controlled biodegradation, the ability to protect cargoes against premature release and unwanted degradation), mesoporous silica particles (MSPs) are emerging as a promising diagnostic and delivery platform with a key role in the development of next-generation theranostics, nanovaccines, and formulations. In this study, MSPs with customized characteristics in-lab prepared were fully characterized and used as carriers for doxorubicin (DOX). The drug loading capacity and the release profile were evaluated in media with different pH values, mimicking the body conditions. The release data were fitted to Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin kinetic models to evaluate the release constant and the mechanism. The in vitro behavior of functionalized silica particles showed an enhanced cytotoxicity on human breast cancer (MCF-7) cells. Bio- and mucoadhesion on different substrates (synthetic cellulose membrane and porcine tissue mucosa)) and antimicrobial activity were successfully assessed, proving the ability of the OH- or the organically modified MSPs to act as antimicrobial and mucoadhesive platforms for drug delivery systems with synergistic effects.

Nitrogen-doped carbon dots for doxorubicin-targeted delivery and two-photon cell imaging

Nitrogen (N) doped CDs (N-CDs) were prepared using citric acid and hexamethylenetetramine by a one-step hydrothermal method, characterized by transmission electron microscopy (TEM), Powder X-ray Diffractometer (PXRD), Nuclear Magnetic Resonance (13C NMR), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), and ultraviolet–visible (UV–vis) absorption spectra. The doping mechanism and drug-loading characteristics of N-CDs were also studied. The results showed that N-CDs had both down- and up-conversion fluorescence properties and the average particle size was about 4.28 nm. N-CDs could be used as a drug carrier for doxorubicin (DOX) (N-CDs-DOX) via the formation of the NC bond, and the drug-loading rate of N-CDs-DOX was 35.88%. The N-CDs-DOX had pH-targeted properties and low cytotoxicity. In vitro release of N-CDs-DOX belonged to the Weibull model and Fick diffusion. The results showed that N-CDs could deliver DOX successfully, and collocate with DOX in the SH-SY5Y cells through two-photon imaging. The N-CDs-DOX system had sustained-release and pH-targeted properties. N-CDs were expected to deliver a type of drugs containing CO group and be used in cancer treatment.

Interaction study of Dox-incorporated AS1411 aptamer and nucleolin by molecular dynamics simulation

ABSTRACT AS1411 aptamer is able to recognise the nucleolin overexpressed on cancer cell membranes and has shown promise as a carrier of doxorubicin (Dox) to the cells. This study aimed to study the interaction between nucleolin and aptamers, in either the absence or presence of Dox, using molecular dynamics simulation. AS22nt aptamer was constructed by joining AS1411 aptamer with an additional 22 nucleotide (nt) sequence. NPT simulations were performed from initial docked configuration predicted by HDOCK. The binding of Dox to AS22nt aptamer occurred at the minor groove and the intercalation site in the duplex region. Nucleolin exhibited less flexibility upon binding to AS22nt. The dominant interaction between nucleolin and AS22nt was the electrostatic interaction. The presence of Dox in AS22nt affected the AS22nt-nucleolin interaction contributed by hydrogen bond, hydrophobic contact and ionic interaction. However, the presence of Dox in AS22nt had no impact on the interaction between nucleolin and AS22nt because the magnitudes of binding energy of nucleolin and aptamer with Dox or without Dox were comparable and they were within their calculated deviation. This understanding of nucleolin, AS1411 aptamer, and Dox interactions could provide us a way to prepare an effective targeted anticancer agent for cancer-suffering patients.