Encapsulation Of Dox Research Articles

A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis

Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.

Synthesis and characterization of the redox-responsive amphiphilic fluorescent alginate derivatives as the multi-functional hydrophobic anticancer drug delivery system with visualization and sustained release

To develop the multi-functional hydrophobic anticancer drug carriers with visualization and sustained release, a novel amphiphilic alginate derivative (LSA-SS-DEAC) containing chromophobe groups was designed and synthesized by grafting hydrophobic fluorescent molecule, 7-(diethylamino-coumarin-3-carboxylic acid (DEAC-COOH) onto hydrophilic low molecular alginate backbone through cystamine by water-soluble carbodiimide chemical method. The molecular structure and self-assembly properties of the synthesized LSA-SS-DEAC were characterized. Furthermore, the encapsulation of anti-cancer drugs, doxorubicin hydrochloride (DOX) in LSA-SS-DEAC self-assembled micelles was realized by ultrasonic dialysis method. Subsequently, the in vitro drug release behavior and in vitro cytotoxicity of LSA-SS-DEAC micelles in simulated tumor microenvironment were also studied. The resultant LSA-SS-DEAC with the critical micelle concentration (CMC) of 0.26 mg/mL exhibited the ability to spontaneously form spherical micelles with the particle size of 250.2 ± 4.3 nm (PDI = 0.23) and zeta potential of −49.1 ± 0.4 mV, which presented good stability in pH 7.4 PBS and excellent fluorescence properties and redox responsiveness. The drug-loaded LSA-SS-DEAC micelles had the optimal EE value of about 42.2% when the DOX/LSA-SS-DEAC mass ratio was 3:10. Meanwhile, The drug-loaded LSA-SS-DEAC micelles exhibited sustained release in GSH-free environment, and the cumulative drug release rates were 40.3% and 46.6% in pH 7.4 and 5.0 PBS for 48 h, respectively. However, in the simulated tumor cell microenvironment (pH 5.0 PBS + 10 mM GSH), the disulfide bond between the core-shell was broken under the GSH trigger, and the LSA-SS-DEAC micelles collapsed, resulting in a cumulative drug release rate of about 64% at 12 h. In vitro cytotoxicity results showed that LSA-SS-DEAC had low cytotoxicity, and revealed obvious inhibitory effect on HeLa cells after DOX loading. Fluorescence imaging results indicated that LSA-SS-DEAC micelles could emit green light after ingested by cells, and their fluorescence properties were not affected after encapsulation of DOX. Accordingly, LSA-SS-DEAC micelles had the potential for drug localization tracking and rapid drug release at focal sites, which could be expected to be an ideal drug carriers for hydrophobic anticancer drug delivery.

Ph-Responsive Drug Delivery System Based on Polymeric Prodrug for Efficient Antitumor Therapy

Ph-responsive micellar nanoparticles in nuclear endosomes were prepared by self-assembling amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) predrugs. Self-assembly of an amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) prodrug was adopted to prepare endosomal pH-responsive micellar nanoparticles, and the encapsulation of free DOX could be made in the hydrophobic core of the nanoparticles by Schiff base bond. These nanoparticles showed great storage steadiness for above 1 week under normal circumstances but disassembled rapidly to answer faintly acidic environment. Thus, we are able to obtain a simple nano-polymer prodrug material that enables efficient and accurate delivery of tumor drugs and can maintain stability in neutral environments and rapidly degrade in the acidic context of tumor cells. In addition, it benefits from the good stability of PSD with high drug loading concentration and long drug release behavior. According to CCK-8 assays, the nanoparticle showed great antitumor activity over free DOX against HeLa tumor cells. These prodrug-based nanomedicines show excellent potential for the development of translational DOX formulations for cancer therapy.

In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole.

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.

Supramolecular nanoparticles based on elastin-like peptides modified capsid protein as drug delivery platform with enhanced cancer chemotherapy efficacy

Cancer, a prevalent disease posing significant threats to human health and longevity, necessitates effective therapeutic interventions. Chemotherapy has emerged as a primary strategy following surgical procedures for combating most malignancies. Despite the considerable efficacy of conventional chemotherapeutic agents against cancer cells, their utility is hindered by profound challenges such as multidrug resistance and deleterious toxic side effects, thereby limiting their systemic application. To tackle these challenges, we have devised a promising nanomedicine platform based on a plant virus. Specifically, we have selected the cowpea melanoma mottled virus (CCMV) as our nano-delivery system owing to its monodisperse and homogeneous size, as well as its intrinsic ability for controlled self-assembly. Leveraging the potential of this platform, we have engineered CCMV-based nanoparticles functionalized with elastin-like peptides (ELPs) at their N-terminal region. The target protein, CP-ELP, was expressed via E.coli, enabling encapsulation of the model drug DOX upon structural domain modification of the protein. The resulting nanoparticles exhibit uniform size distribution, facilitating efficient internalization by tumor cells and subsequent intracellular drug release, leading to enhanced antitumor efficacy. In addition, EVLP@DOX nanoparticles were found to activate immune response of tumor microenvironment in vivo, which further inhibiting tumor growth. Our designed nanoparticles have also demonstrated remarkable therapeutic effectiveness and favorable biological safety profiles in both murine melanoma and colorectal cancer models.

Collaborative CuMn diatomic nanozyme to boost nanocatalytic/mild photothermal/chemo-therapy through overcoming therapeutic resistance

The combined mild-temperature photothermal/chemo-therapy has emerged as a promising approach to complement traditional tumor treatment and enhance therapeutic effects while reduce side effects. However, therapeutic resistance caused by up-regulation of heat shock proteins (HSPs) and P-glycoprotein (P-gp) drastically compromises the synergetic therapeutic effect. Herein, we develop a multifunctional CuMn dual-atom nanozyme loaded with the chemotherapeutic agent doxorubicin (DOX@CuMn-DAzymes) for P-gp and HSPs simultaneous silencing induced synergistic trimodal therapy. The resulting CuMn double-atom pairs with significant synergistic effects can efficiently catalyze cascade reactions of catalase (CAT)-like and oxidase (OXD)-like with endogenous H2O2 as the initial reactant to produce highly reactive singlet oxygen (1O2) under the trigger of acidic tumor microenvironment, destroying the P-gp and HSPs in tumor cells. Benefitting from their black polyporous nanocarbon support, DOX@CuMn-DAzymes not only show superior 1064 nm laser triggered photothermal performance, but also possess high DOX encapsulation efficiency and dual pH- and NIR-responsive DOX release properties. Moreover, in vitro and in vivo study results demonstrate that DOX@CuMn-DAzymes effectively overcome therapeutic resistance by boosting intracellular 1O2 level to simultaneously silence P-gp and HSPs, thereby achieving an impressive synergetic therapeutic efficacy.

Polymeric graphene oxide nanoparticles loaded with doxorubicin for combined photothermal and chemotherapy in triple negative breast cancer

Combining photothermal and chemotherapy is an emerging strategy for tumor irradiation in a minimally invasive manner, utilizing photothermal transduction agents and anticancer drugs. The present work developed a 2D carbon nanomaterial graphene oxide (GO)-based nanoplatform that converted to 3D colloidal spherical structures upon functionalization with an amphiphilic polymer mPEG-PLA (1, 0.5/1/2) and entrapped doxorubicin (Dox) physically. The Dox@GO(mPP) (1/0.5) NPs displayed the least particle size (161 nm), the highest stability with no aggregation, the highest Dox loading (6.3 %) and encapsulation efficiency (70 %). The therapeutic efficacy was determined in vitro and in vivo using murine (4 T1) and human triple-negative breast cancer cells (MDA-MB-231), and 4 T1-Luc-tumor bearing mouse models. The results demonstrated that the Dox@GO(mPP) (1/0.5) NPs treatment with laser (+L) (808 nm) was highly efficient in inducing apoptosis, cell cycle arrest (G2/M) phase, significant cytotoxicity, mitochondrial membrane depolarization, ROS generation, and photothermal effect leading to a higher proportion of cell death than free Dox, and Dox@GO(mPP) (1/0.5) NPs (−L). The anticancer studies in mice harboring the 4 T1-Luc tumor showed that combination of Dox@GO(mPP) (1/0.5) NPs (+L) effectively reduced tumor development and decreased lung metastasis. The developed nanoplatform could be a promising combination chemo-photothermal treatment option for triple-negative breast cancer.

A Review of Colon Cancer Treatment using Photoactive Nanoparticles

This reviewed work on the development of photosensitive nanoparticles (NPs) based on a photodegradable poly(o-nitrobenzyl acrylate) core (PNBA, a hydrophobic and biocompatible polymer) and a dextran-derived shell (dextran is a biodegradable and water-soluble bacterial polysaccharide). First, methods for synthesizing PNBA-N3 were demonstrated by 1) single electron transfer radical polymerization (SET-LRP) of o-nitrobenzyl acrylates and then 2) introducing a single azide end functionalization. At the same time, the processes for the production of DexAlkyne-15 bearing several alkyne groups by the hydrophilicity of dextran were also addressed. Such as DexAlkyne-15 and PNBA-N3 can be reacted by CuAAC (Cu(I)-azide-alkyne cycloaddition catalyst) chemically resulting in Dex-g-PNBA glycopolymers with different molecular parameters. Second, strategies for producing NPs were demonstrated by comparing two processes that were characterized in terms of size, amount of dextran, coat thickness, and colloidal stability in NaCl or cell culture medium, or in the presence of a single potent surfactant. On the one hand, NPs made by nanodeposition of Dex-g-PNBA exhibit high PNBA weight fractions (>40%). On the other hand, the NPs were produced by evaporating the emulsion to the organic solvent using DexAlkyne-15 as a water-soluble surfactant and PNBA-N3 as a hydrophobic material. In this case, CuAAC occurred in situ (or not) at the fluid/liquid interface during the formulation of the NPs, resulting in “clicking” and “non-clicking”. Finally, a systematic study of the disorder of NPs by ultraviolet irradiation according to photolysis of PNBA chains is shown. To use NPs as smart drug delivery systems, studies have been shown of loading Doxorubicin (DOX - an anti-cancer agent) into NPs during placement. Methods for optimizing experimental conditions to enhance DOX encapsulation are discussed.

Strategies of stabilization of zein nanoparticles containing doxorubicin hydrochloride

Hybrid nanoparticles made up of zein and various stabilizers were developed and characterized. In detail, a zein concentration of 2 mg/ml was blended with various amounts of different phospholipids or PEG-derivatives in order to obtain formulations with suitable physico-chemical properties for drug delivery purposes. Doxorubicin hydrochloride (DOX) was used as a model of a hydrophilic compound and its entrapment efficiency, release profile and cytotoxic activity were investigated. Photon correlation spectroscopy showed that the best formulations were obtained using DMPG, DOTAP and DSPE-mPEG2000 as stabilizers of zein nanoparticles, which were characterized by an average diameter of ~100 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The interaction between protein and stabilizers was confirmed through FT-IR analysis, while TEM analysis showed the presence of a shell-like structure around the zein core. The release profiles of the drug from the zein/DSPE-mPEG2000 nanosystems, evaluated at two pHs (5.5 and 7.4), showed a prolonged and constant leakage of the drug. The encapsulation of DOX within zein/DSPE-mPEG2000 nanosystems did not compromise its biological efficacy, demonstrating the potential application of these hybrid nanoparticles as drug carriers.

Theranostic doxorubicin encapsulated FeAu alloy@metal-organic framework nanostructures enable magnetic hyperthermia and medical imaging in oral carcinoma

Metal-organic frameworks (MOFs) have emerged as attractive candidates in cancer theranostics due to their ability to envelop magnetic nanoparticles, resulting in reduced cytotoxicity and high porosity, enabling chemodrug encapsulation. Here, FeAu alloy nanoparticles (FeAu NPs) are synthesized and coated with MIL-100(Fe) MOFs to fabricate FeAu@MOF nanostructures. We encapsulated Doxorubicin within the nanostructures and evaluated the suitability of this platform for medical imaging and cancer theranostics. FeAu@MOF nanostructures (FeAu@MIL-100(Fe)) exhibited superparamagnetism, magnetic hyperthermia behavior and displayed DOX encapsulation and release efficiency of 69.95 % and 97.19 %, respectively, when stimulated with alternating magnetic field (AMF). In-vitro experiments showed that AMF-induced hyperthermia resulted in 90 % HSC-3 oral squamous carcinoma cell death, indicating application in cancer theranostics. Finally, in an in-vivo mouse model, FeAu@MOF nanostructures improved image contrast, reduced tumor volume by 30-fold and tumor weight by 10-fold, which translated to enhancement in cumulative survival, highlighting the prospect of this platform for oral cancer treatment.

Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies

Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administration. Herein, to address this issue, injectable and TME-responsive nanocomposite hydrogels were developed for localized and synergistic cancer therapy. The nanocomposite hydrogels (Au NBPs&Pt NCs@DOX gel) were synthesized via the formation of metal-sulfur bonds between 4arm-PEG-thiol and Au nanobipyramids or Pt nanoclusters with the DOX encapsulation. The hydrogel exhibited rapid gelation and excellent injectability. Attributed to the high absorbance of Au NBPs, the nanocomposite hydrogels revealed superior photothermal effect under NIR irradiation, which the DOX release was also regulated by NIR laser. In addition, the catalase- and peroxidase-like activities of Pt NCs were validated to convert endogenous H2O2 into ROS and O2 in situ to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Simultaneously, catalytic therapy combined with NIR irradiation exhibited strongest inhibition to the growth of 4T1 tumor in vitro and in vivo. Thus, this study provided a new strategy for TME remodeling and local combination therapies of different therapeutic agents.

Multifunctional Folic acid‐coated and Doxorubicin Encapsulated Mesoporous Silica Nanocomposites (FA/DOX@Silica) for Cancer Therapeutics, Bioimaging and invitro Studies

AbstractCancer is a cluster of diseases, which caused by the mutation in cells and it has the potential to cover any part of the body. The whole world is vigorously struggling to find a safe approach to cure the cancer. The classical chemotherapy approach involves the use of chemotherapeutic agents to kill cancer cells. The major disadvantage of therapy is less in vivo stability and negatively affects the healthy cells. Nowadays, the targeted drug delivery techniques has gained lots of interest, because of the efficient drug release at the cancerous sites. Herein, we have synthesized Folic acid (FA) coated and Doxorubicin drug (Dox) encapsulated mesoporous silica nanocomposites (FA/Dox@Silica)for targeted delivery of DOX and bioimaging. Encapsulation of Dox was done to make it more stable in the cell atmosphere and for its controlled release. The coating of FA makes these nanocomposites makes them an vehical for chemically targeted delivey of DOX, as it was already confirmed by several studies that there are folate receptors present over cancer cells and these reseptors are responsive towards the FA Thus these nanocomposites can be easily recognized by the cancer cells and they can efficiently deliver drugs. The shape, size, morphology, crystallinity, porosity, and fictionalizations were analyzed by using several characterization techniques such as DLS, TEM, and FTIR. The drug loading was confirmed qualitatively by using optical spectroscopic techniques. The drug release pattern was studiedfor the 15 days which showed the sustained and regulated release of drug from the mesoporous silica nanocomposites. Cellular uptake was observed by cell staining assay confirmed the fair uptake of nanoparticles.

A liposomal formulation of simvastatin and doxorubicin for improved cardioprotective and anti-cancer effect

Anthracyclines such as doxorubicin (Dox) are the preferred chemotherapeutics for several cancers. However, Dox-induced cardiotoxicity limits its therapeutic potential. Liposomal encapsulation of Dox has been used for patients with risk to develop Dox induced cardiotoxicity but does not surpass the efficacy of the unencapsulated drug. Statins are widely used as cholesterol lowering drugs and have also demonstrated cardioprotective activity in cancer patients undergoing Dox therapy. We developed a liposome loaded with Dox and simvastatin (Sim) and investigated their effect on cardiomyocytes and zebrafish larvae. Furthermore, we investigated if the doses required for cardioprotection compromised the cytotoxicity of Dox in mammary and prostate cancer cells. Combination of Sim and Dox reduced ROS generation in cardiomyocytes, both given as free drugs, or co-encapsulated in liposomes. In contrast, Sim potentiated ROS-generation and cytotoxic activity of Dox towards cancer cells also when co-encapsulated in liposomes. In zebrafish larvae, Sim treatment reduced Dox-induced cardiac affection, and the liposomes did not induce any sign of Dox-induced cardiotoxicity. Our results show that liposomal co-encapsulation of Sim and Dox can be an efficient way of further reducing the risk of cardiotoxic events of liposomal Dox, while retaining, or even potentiating the anti-cancer effect of Dox.

Synthesis of doxorubicin-loaded peptosomes hybridized with gold nanorod for targeted drug delivery and CT imaging of metastatic breast cancer

BackgroundCancer nanomedicines based on synthetic polypeptides have attracted much attention due to their superior biocompatibility and biodegradability, stimuli responsive capability through secondary conformation change, adjustable functionalities for various cargos such as peptides, proteins, nucleic acids and small therapeutic molecules. Recently, a few nanoformulations based on polypeptides comprising NK105, NC6004, NK911, CT2103, have entered phase I-III clinical trials for advanced solid tumors therapy. In the current study, we prepared polypeptide-based vesicles called peptosome via self-assembly of amphiphilic polypeptide-based PEG-PBLG diblock copolymer.ResultsIn this regard, poly(γ-benzyl L-glutamate (PBLG) was synthesized via ring opening polymerization (ROP) of γ-benzyl L-glutamate-N-carboxyanhydride (BLG-NCA) using N-hexylamine as initiator. Then amine-terminated PBLG was covalently conjugated to heterofuctional maleimide PEG-carboxylic acid or methyl-PEG-carboxylic acid. The PEG-PBLG peptosomes were prepared through double emulsion method for the co-delivery of doxorubicin.HCl and gold nanorods as hydrophilic and hydrophobic agents in interior compartment and membrane of peptosomes, respectively (Pep@MUA.GNR-DOX) that DOX encapsulation efficiency and loading capacity were determined 42 ± 3.6 and 1.68 ± 3.6. Then, theranostic peptosomes were decorated with thiol-functionalized EpCAM aptamer throught thiol-maleimide reaction producing Apt-Pep@MUA.GNR-DOX for targeted delivery. The non-targeted and targeted peptosomes showed 165.5 ± 1.1 and 185 ± 4.7 nm diameters, respectively while providing sustained, controlled release of DOX. Furthermore, non-targeted and targeted peptosomes showed considerable serum stability. In vitro study on MCF-7 and 4T1 cells showed significantly higher cytotoxicity for Apt-Pep@MUA.GNR-DOX in comparison with Pep@MUA.GNR-DOX while both system did not show any difference in cytotoxicity against CHO cell line. Furthermore, Apt-Pep@MUA.GNR-DOX illustrated higher cellular uptake toward EpCAM-overexpressing 4T1 cells compared to Pep@MUA.GNR-DOX. In preclinical stage, therapeutic and diagnostic capability of the prepared Pep@MUA.GNR-DOX and Apt-Pep@MUA.GNR-DOX were investigated implementing subcutaneous 4T1 tumor model in BALB/c mice. The obtained data indicated highest therapeutic index for Apt-Pep@MUA.GNR-DOX compared to Pep@MUA.GNR-DOX and free DOX. Moreover, the prepared system showed capability of CT imaging of tumor tissue in 4T1 tumorized mice through tumor accumulation even 24 h post-administration.ConclusionIn this regard, the synthesized theranostic peptosomes offer innovative hybrid multipurpose platform for fighting against breast cancer.Graphical

Single-particle assessment of six different drug-loading strategies for incorporating doxorubicin into small extracellular vesicles.

Extracellular vesicles (EVs) have emerged as an attractive drug delivery system owing to their natural roles in intercellular communication. On account of the large intrinsic heterogeneity of EVs, it is highly desirable to evaluate not only the encapsulation efficiency but also the alteration of biological functionality after the drug-loading process at the single-particle level. However, the nanoscale size of EVs poses a great challenge. Taking advantage of nano-flow cytometry (nFCM) in the multiparameter analysis of single EVs as small as 40nm, six commonly used drug-loading strategies (coincubation, electroporation, extrusion, freeze-thawing, sonication, and surfactant treatment) were exploited by employing doxorubicin (Dox) as the model drug. Encapsulation ratio, EV concentration, drug content, and membrane proteins of Dox-loaded EVs were measured at the single-particle level. Our data indicated that coincubation and electroporation outperformed other methods with an encapsulation ratio of approximately 45% and a higher Dox content in single EVs. Interestingly, the labeling ratios of membrane proteins indicated that varying degrees of damage to the surface proteins of EVs occurred upon extrusion, freeze-thawing, sonication, and surfactant treatment. Confocal fluorescence microscopy and flow cytometry analysis revealed that Dox-loaded EVs prepared by electroporation induced the strongest apoptosis followed by coincubation. These results correlated well with their cellular uptake rate and fundamentally with the Dox encapsulation efficiency of single EVs. nFCM provides a rapid and sensitive platform for single-particle assessment of drug-loading strategies for incorporating drugs into EVs.

Functionalized Mesoporous Silica as Doxorubicin Carriers and Cytotoxicity Boosters.

Mesoporous silica nanoparticles (MSNs) bearing methyl, thiol or glucose groups were synthesized, and their encapsulation and release behaviors for the anticancer drug Doxorubicin (Dox) were investigated in comparison with nonporous homologous materials. The chemical modification of thiol-functional silica with a double bond glucoside was completed for the first time, by green thiol-ene photoaddition. The MSNs were characterized in terms of structure (FT-IR, Raman), morphology (TEM), porosity (nitrogen sorption–desorption) and Zeta potential measurements. The physical interactions responsible for the Dox encapsulation were investigated by analytic methods and MD simulations, and were correlated with the high loading efficiency of MSNs with thiol and glucose groups. High release at pH 5 was observed in most cases, with thiol-MSN exhibiting 98.25% cumulative release in sustained profile. At pH 7.4, the glucose-MSN showed 75.4% cumulative release, while the methyl-MSN exhibited a sustained release trend. The in vitro cytotoxicity was evaluated on NDHF, MeWo and HeLa cell lines by CellTiter-Glo assay, revealing strong cytotoxic effects in all of the loaded silica at low equivalent Dox concentration and selectivity for cancer cells. Atypical applications of each MSN as intravaginal, topical or oral Dox administration route could be proposed.

New anti-tumor strategy based on acid-triggered self-destructive and near-infrared laser light responses of nano-biocatalysts integrating starvation–chemo–photothermal therapies

BackgroundInherent limitations of single cancer therapy are overcome by multi-therapy modality, which integrates characteristics of each therapeutic modality and material chemistry. The multi-modal method has the potential for becoming one of the next generation options for cancer treatments. Photothermal therapy (PTT) is an efficient, non-invasive treatment method that can be used on various cancer types. We propose an acid-triggered self-destructing nano-biocatalyst integrated starvation/chemical/photothermal triple therapy that is based on design principles and biomedical applications of GOx cancer treatment methods.MethodsScanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials were used to analyze the physical as well as chemical properties of MoS2@DOX/GOx@MnO2 (M@D/G@M). Further, Fourier transform infra-red (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were used to assess the compositions of the nanocatalysts. The biological effects of M@D/G@M on cells were studied in vitro by inverted fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry, CCK-8 test, and hemolysis test. Treatment effects of the nanocatalysts were evaluated in MHCC-97H tumor BALB/c mice, whose body weights, tumor local temperature, tumor volumes, and tumor histological changes were evaluated.ResultsThere was a high DOX encapsulation efficiency of M@D/G@M (90.233%). The photothermal conversion efficiency (η) of M@D/G@M is 25.2%, and its oxygen production within 5 min reached 27.5 mg L−1. Cell internalization analysis showed that within 4 h, M@D/G@M was almost completely absorbed by HepG2 cells. Further, the highest red fluorescence and apoptosis effects of dead cells (59.07% apoptosis) as well as the lowest tumor volume index of mice (0.2862%) were observed in the M@D/G@M + pH6.0 + NIR treatment group.ConclusionsOur findings inform the development and applications of multi-modal methods in tumor therapy.

Removal of doxycycline hydrochloride from aqueous solution by rice husk ash using response surface methodology and disposability study.

The huge demand and consumption of DOX, its incomplete metabolism, and complex behavior in atmosphere are causing a great ecological issue, which needs to be solved. In the present study, the suitability of rice husk ash (RHA) for the greater sorption efficiency of DOX antibiotic was investigated. Furthermore, disposability study of exhausted RHA was performed using solidification technique and leachate had undergone toxicity test to evaluate the DOX encapsulation ability. The central composite design under RSM was employed for the design of experiment and optimization of adsorption parameters. RHA was characterized using various techniques such as XRD, SEM (EDX), FTIR, BET, and zeta potential analysis. The influence of various adsorption parameters, like initial DOX concentration (C0), RHA dosage (m), incubation-time period (t), and pH were examined on the performance in terms of DOX elimination % (X1) and adsorptive capacity (mg/g) (X2). At optimized conditions, the obtained X1 and X2 were 98.85% and 17.74 mg/g, respectively. Moreover, the kinetics data suited well to the pseudo–second-order model. Freundlich, Langmuir, and Redlich-Peterson (R-P) isotherm models were applied, out of which Langmuir model best performed under optimized conditions; m = 5 g/L, t = 85.85 min, DOX concentration = 89.73 mg/L, and pH = 6. The bacterial toxicity test of leachate confirmed complete encapsulation of DOX by solidification technique.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-022-18961-1.

Adsorptive decontamination of doxycycline hydrochloride via Prosopis juliflora activated carbon: Parameter optimization and disposal study

This study deals with the removal of doxycycline hydrochloride (DOX) antibiotic, from aqueous environment by using Prosopis juliflora activated carbon (PJAC). PJAC was synthesized by chemical activation and pyrolysis of Prosopis juliflora. It was characterized by employing Fourier transform infrared spectroscopy (FTIR), scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), X-ray diffraction analysis (XRD), and Brunauer-Emmett-Teller (BET) techniques. The specific surface area, pore volume, and pore diameter were evaluated as 320.45 m2 /g, 0.176 cm3 /g, and 2.65 nm, respectively. Different functional groups (O-H, C-O, C=C, C-N, and C-C) present on PJAC promoted the adsorption of DOX. The influence of various adsorption parameters suggested by central composite design (CCD) model was determined using response surface methodology (RSM), and interactive effects of these were optimized. The thermodynamic and kinetic studies performed at optimized conditions, exhibited that adsorption was spontaneous and endothermic. The experimental data were well described with Langmuir, Redlich-Peterson, and Freundlich isotherm models while kinetics data were well described by pseudo second order. The excellent interactions between the PJAC and DOX resulted maximum adsorption capacity as 57.11 mg/g. The adsorption mechanisms was dominated by - interactions and hydrogen bonding. Moreover, almost complete encapsulation of DOX was achieved by stabilization of exhausted PJAC. PRACTITIONER POINTS: A wild harmful plant Prosopis juliflora was used to synthesize a low-cost and eco-friendly bio-sorbent PJAC. Adsorptive ability of PJAC was quantified for adsorption of DOX antibiotic from its aqueous solution. DOX uptake on PJAC was mainly governed by л-л EDA interactions and hydrogen bonding.

Chitosan-coated poly (lactic-co-glycolide) nanoparticles for dual delivery of doxorubicin and naringin against MCF-7 cells

Present investigation examines the simultaneous encapsulation and delivery of DOX and NAR through PLGA-NPs and CS-coated PLGA-NPs to improve the efficacy and synergistic anticancer activity of DOX, and reduce its toxicity. Drug-loaded F3 and F4 were prepared by double-emulsion solvent-evaporation technique. PS, PDI, ZP and morphology of the NPs were determined using Zetasizer and SEM, respectively. %EE and %DL of both drugs were determined by indirect method. Dialysis tubing was used for in vitro release studies in phosphate buffer saline (pH 6.8) with SLS (0.1% w/v). Storage stability of the NPs was performed at 30 °C for 6-months. In vitro cytotoxicity was determined by MTT-assay, using MCF-7 cells. Cytotoxic effects of the NPs were also observed by visualizing the morphological changes in MCF-7 cells. PS, PDI and ZP of F4 were 366.8 ± 36.7 nm, 0.352 ± 0.033 and +35.57 ± 4.25 mV, respectively and those of F3 were 302.2 ± 45.4 nm, 0.283 ± 0.016 and −4.69 ± 2.66 mV. Increased PS and high positive ZP were found after CS-coating. Smooth-surfaced PLGA-NPs were observed by SEM, and slightly rough-surfaced NPs were found after CS-coating. %EE and %DL for DOX were 66.01%, 4.26% and 76.26%, 3.28% in F3 and F4, respectively. For NAR, these values were 77.82%, 3.22% and 71.85%, 4.64% in F3 and F4. The in vitro release profile revealed a sustained delivery of the drugs with 51% and 63% of DOX, as well as 80% and 78% of NAR at 48 h, from F3 and F4, respectively. Relatively high amounts of DOX and NAR were rapidly released from DOX-NAR-AqS at 2 h only. Release kinetic investigations justify the sustained release property of F3 and F4, and they followed the “Korsmeyer-Peppas model”. Release-exponent values suggest that the mechanism of the drug(s) release was Fickian-diffusion. Stability study revealed acceptable physicochemical changes for 6-months F4 showed the highest cytotoxicity (IC50, 1.52 μg/mL), when compared to F3, free DOX-NAR combination and DOX alone. Cytotoxicity and cell morphology represented the highest cellular uptake of F4. Conclusively, F4 could be an effective nano-carrier for DOX and NAR to improve their encapsulation, sustain their release, stability and simultaneous delivery against MCF-cells.