An exosomal approach for oral delivery of resveratrol: Implications for inflammatory bowel disease treatment in rat model.

AIMS: Resveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches. MAIN METHODS: The current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models. KEY FINDINGS: The results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis. SIGNIFICANCE: Our findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations.

FOXM1 Aptamer-Polyethylenimine Nanoplatform Coated With Hyaluronic Acid And AS1411 Aptamer For Dual-Targeted Delivery of Doxorubicin And Synergistic Treatment of Tumor Cells.

The objective of this investigation was to develop a self-assembled, dual-functionalized delivery system that could effectively transport doxorubicin (DOX) to cancer cells through the use of AS1411 aptamer and hyaluronic acid polymer (HA). The ultimate goal is an improved targeting approach for more efficient treatment. The core of this system comprised polyethylenimine (PEI) and FOXM1 aptamer, which was coated by HA. Next, nucleolin targeting aptamers (AS1411) were loaded onto the nanocomplex. Afterward, DOX was added to Aptamers (Apts)-HA-PEI-FOXM1 NPs to create the DOX-AS1411-HA-PEI-FOXM1 NPs for better treatment of cancer cells. The cytotoxic effect of the nanocomplex on L929, 4T1, and A549 cells showed that cell mortality in target cancer cells (4T1 and A549) was considerably enhanced compared to nontarget cells (L929, normal cells). The findings from the flow cytometry analysis and fluorescence imaging demonstrated the cellular absorption of DOX-Apts-HA-PEI-FOXM1 NPs in target cells was significantly enhanced when compared to L929 cells. Furthermore, in vivo antitumor study exhibited that DOX-Apts-HA-PEI-FOXM1 NPs rendered specific tumor accumulation and increasing of the anti-tumor effects.

Surface modification of hollow gold nanoparticles conducted by incorporating cancer cell membrane and AS1411 aptamer, aiming to achieve a dual-targeted therapy for colorectal cancer.

Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer.

Sandwich-type aptamer-based biosensors for thrombin detection.

Thrombin, a proteolytic enzyme, plays an essential role in catalyzing many blood clotting reactions. Thrombin can act as a marker for some blood-related diseases, such as leukemia, thrombosis, Alzheimer's disease and liver disease. Therefore, its diagnosis is of great importance in the fields of biological and medical research. Biosensors containing sandwich-type structures have attracted much consideration owing to their superior features such as reproducible and stable responses with easy improvement in the sensitivity of detection. Sandwich-type platforms can be designed using a pair of receptors that are able to bind to diverse locations of the same target. Herein, we investigate recent advances in the progress and applications of thrombin aptasensors containing a sandwich-type structure, in which two thrombin-binding aptamers (TBAs) identify different parts of the thrombin molecule, leading to the formation of a sandwich structure and ultimately signal detection. We also discuss the pros and cons of these approaches and outline the most logical approach in each section.

Improving Chemotherapy Effectiveness: Utilizing CuS Nanoparticles Coated with AS1411 Aptamer and Chitosan for Targeted Delivery of Doxorubicin to Cancerous Cells.

Here, a novel targeted nanostructure complex was designed as an alternative to the traditional treatment approaches for breast cancer. A delivery system utilizing CuS nanoparticles (CuS NPs) was developed for the purpose of targeted administration of doxorubicin (Dox), an anticancer agent. To regulate Dox release, chitosan (CS), a biodegradable and hydrophilic polymer with biocompatible properties, was applied to coat the Dox-loaded CuS NPs. Furthermore, AS1411 aptamer, served as a targeting agent for breast cancer cells (MCF-7 and 4T1 cells), was conjugated with CS-Dox-CuS NPs effectively. To assess the effectiveness of APT-CS-CuS NPs, various methods such as flow cytometry analysis, MTT assay, fluorescence imaging, and in vivo antitumor efficacy were employed. The hollow core and porous surface of CuS NPs improved the Dox loading capacity and entrapment efficiency (almost 100%). The rate of drug release at the tumor site (citrate buffer with pH 5.6) exhibited a marked increase in comparison to that observed within the physiological environment (phosphate buffer with pH 7.4). The targeted formulation (APT-CS-Dox-CuS NPs) significantly increased cytotoxicity of the Dox payload in target cells, including 4T1 (p ≤ 0.0001 (****)) and MCF7 (p ≤ 0.01 (**)) cells compared to CHO cells. Moreover, the ability of tumor growth inhibition of the targeted system was significantly (p ≤ 0.05 (*)) more than free Dox in tumor-bearing mice. The findings indicate that the targeted formulation augmented effectiveness and specificity while minimizing harm to non-targeted cells, signifying its potential as a sophisticated cancer drug delivery system.

Molecular dynamics simulation as a promising approach for computational study of liquid crystal-based aptasensors.

As a potent computational methodology, molecular dynamics (MD) simulation provides advantageous knowledge about biological compounds from the molecular viewpoint. In particular, MD simulation gives exact information about aptamer strands, such as the short synthetic oligomers, their orientation, binding sites, folding-unfolding state, and conformational re-arrangement. Also, the effect of the different chemicals and biochemicals as the components of aptamer-based sensors (aptasensors) on the aptamer-target interaction can be investigated by MD simulation. Liquid crystals (LCs) as soft substances with characteristics of both solid anisotropy and liquid fluidity are new candidates for designing label-free aptasensors. To now, diverse aptasensors have been developed experimentally based on the optical anisotropy, fluidity, and long-range orientational order of LCs. Here, we represent a computational model of an LC-based aptasensor through a detailed MD simulation study. The different parameters are defined and studied to achieve a comprehensive understanding of the computational design of the LC-based aptasensor, including the density of LCs, their orientation angle, and lognormal distribution in the absence and presence of aptamer strands, both aptamer and target molecules with various concentrations, and interfering substance. As a case study, the tobramycin antibiotic is considered the target molecule for the computational model of the LC-based aptasensor.Communicated by Ramaswamy H. Sarma.

Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation.

One of the revolutionized cancer treatment is active targeting nanomedicines. This study aims to create a dual-targeted drug delivery system for Epirubicin (EPI) to cancer cells. Hyaluronic acid (HA) is the first targeting ligand, and 5TR1 aptamer (5TR1) is the second targeting ligand to guide the dual-targeted drug delivery system to the cancer cells. HA is bound to highly expressed receptors like CD44 on cancer cells. 5TR1, DNA aptamer, is capable of recognizing MUC1 glycoprotein, which is overexpressed in cancer cells. The process involved binding EPI and 5TR1 to HA using adipic acid dihydrazide (AA) as a linker. The bond between the components was confirmed using 1H NMR. The binding of 5TR1 to HA-AA-EPI was confirmed using gel electrophoresis. The particle size (132.6 ± 9 nm) and Zeta Potential (-29 ± 4.4 mV) were measured for the final nanoformulation (HA-AA-EPI-5TR1). The release of EPI from the HA-AA-EPI-5TR1 nanoformulation was also studied at different pH levels. In the acidic pH (5.4 and 6.5) release pattern of EPI from the HA-AA-EPI-5TR1 nanoformulation was higher than physiological pH (7.4). The cytotoxicity and cellular uptake of the synthetic nanoformula were evaluated using MTT and flow cytometry analysis. Flow cytometry and cellular cytotoxicity studies were exhibited in a negative MUC1-cell line (CHO) and two positive MUC1+cell lines (MCF-7 and C26). Results confirmed that there is a notable contrast between the dual-targeted (HA-AA-EPI-5TR1) and single-targeted (HA-AA-EPI) nanoformulation in MCF-7 and C26 cell lines (MUC1+). In vivo studies showed that HA-AA-EPI-5TR1 nanoformulation has improved efficiency with limited side effect in C26 tumor-bearing mice. Also, Fluorescence imaging and pathological evaluation showed reduced side effects in the heart tissue of mice receiving HA-AA-EPI-5TR1 than free EPI. So, this targeted approach effectively delivers EPI to cancer cells with reduced side effects.

CRISPR-Cas12a-based colorimetric aptasensor for aflatoxin M1 detection based on oxidase-mimicking activity of flower-like MnO2 nanozymes.

Given the highly mutagenic and carcinogenic nature of Aflatoxin M1 (AFM1), the quantity assessment of AFM1 residues in milk and dairy products is necessary to maintain consumer health and food safety. Herein, CRISPR-Cas12a-based colorimetric aptasensor was developed using the catalytic activity of flower-like nanozymes of MnO2 and trans-cleavage property of CRISPR-Cas12a system to quantitatively detect AFM1. The basis of the developed colorimetric aptasensor relies on whether or not the CRISPR-Cas12a system is activated, as well as the contrast in oxidase-mimicking capability exhibited by flower-like MnO2 nanozymes when AFM1 is absent or present. When AFM1 is not present in the sample, single-stranded DNA (ssDNA) is degraded by the activated CRISPR-Cas12a, and the solution turns into yellow due to the catalytic activity of the nanozymes. While, in the attendance of AFM1, ssDNA degradation does not occur due to the inactivation of the CRISPR-Cas12a. Therefore, with the adsorption of the ssDNA on the MnO2 nanozymes, their catalytic activity decreases, and the solution color becomes pale yellow due to less oxidation of the chromogenic substrate. In this aptasensor, the relative absorbance changes increased linearly from 6 to 160 ng L-1, and the detection limit was 2.1 ng L-1. The developed aptasensor displays a selective detection performance and a practical application for quantitative analysis of AFM1 in milk samples. The results of the introduced aptasensor open up the way to design other selective and sensitive aptasensors for the detection of other mycotoxins by substitution of the used sequences.

Signal-off nanozyme-based colorimetric aptasensor for sensitive detection of ampicillin using MnO2 nanoflowers and gold nanoparticles.

The combination of nanomaterials possessing distinct characteristics and the precision of aptamers facilitates the creation of biosensors that exhibit exceptional selectivity and sensitivity. In this manuscript, we present a highly sensitive aptasensor that utilizes the distinctive characteristics of MnO2 nanoflowers and gold nanoparticles to selectively detect ampicillin (AMP). In this aptasensor, the mechanism of signal change is attributed to the difference in the oxidase-mimicking activity of MnO2 nanoflowers in the presence of a free sequence. The inclusion of AMP hindered the creation of a double-stranded DNA configuration through its binding to the aptamer, resulting in an observable alteration in absorbance. The relative absorbance varied linearly with the concentration of AMP in the range of 70 pM to 10 nM with a detection limit of 21.7 pM. In general, the colorimetric aptasensor that has been developed exhibits exceptional selectivity and remarkable stability. It also demonstrates favorable performance in human serum, making it a highly reliable diagnostic tool. Additionally, its versatility is noteworthy as it holds great potential for detecting various antibiotics present in complex samples by merely replacing the utilized sequences with new ones.

A Simple Aptamer-Based Nanoconjugate Assay for Diagnosis of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) as a bone marrow stem cell clonal disease appears from the proliferation of granulocyte cells at all stages of maturation. If the disease diagnosis is not early, patients enter the blastic phase, which decreases their survival rate to 3-6 months. It implies the significance of the early diagnosis of CML. In this study, we introduce a simple array for diagnosis of the K562 cells as the human immortalized myeloid leukemia cell line. The developed aptamer-based biosensor (aptasensor) includes the T2-KK1B10 aptamer strands attached to the surface of mesoporous silica nanoparticles (MSNPs) with the cavities accumulated from rhodamine B and coated by both Ca2+ ions and ATP aptamer. The aptamer-based nanoconjugate can enter the K562 cells through the complexation of the T2-KK1B10 aptamer with the cells. The ATP in the cells and low level of intracellular Ca2+ ion release both the aptamer and ion from the surface of the MSNPs. The liberated rhodamine B results in an increased fluorescence intensity. Fluorescence microscope imaging and flow cytometry histogram display a strong fluorescence emission for the K562 cells (CML cells) exposed to the nanoconjugate in comparison with that for MCF-7 cells. The aptasensor possesses good performance in the blood samples with the advantages of high sensitivity, rapidness, and cost-effectiveness, making it an appropriate tool for the diagnosis of CML disease.

Transitional Insight into the RNA-Based Oligonucleotides in Cancer Treatment.

Conventional cancer therapies with chemodrugs suffer from various disadvantages, such as irreversible side effects on the skin, heart, liver, and nerves with even fatal consequences. RNA-based therapeutic is a novel technology which offers great potential as non-toxic, non-infectious, and well-tolerable platform. Herein, we introduce different RNA-based platforms with a special focus on siRNA, miRNA, and mRNA applications in cancer treatment in order to better understand the details of their therapeutic effects. Of note, the co-delivery of RNAs with other distinct RNA or drugs has provided safe, efficient, and novel treatment modalities for cancer treatment.

Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo.

Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of - 23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-responsive sustained drug release profile over a period of 240 h following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments demonstrated that the targeted nanodelivery system provided selective internalization and strong growth inhibition effects of about 45 and 51% against nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that these phenomena were not observed in nucleolin-negative cells (CHO). The preclinical studies revealed that a single-dose intravenous injection of the targeted nanodelivery system into 4T1-bearing mice inhibited tumor growth by 1.7- and 1.4-fold more efficiently than the free drug and the non-targeted nanodelivery system, respectively. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.

A Novel Fluorescent DNA Sensor for Acrylamide Detection in Food Samples Based on Single-Stranded DNA and GelRed.

The presence of acylamide (AA) in large group of food products and its health hazards have been confirmed by scientists. In this study, a simple and innovative biosensor for AA determination was designed based on single-stranded DNA (ssDNA) with partial guanine and GelRed. The idea of this biosensor is based on the formation of AA-ssDNA adduct through the strong binding interaction between AA and guanine base of ssDNA, which subsequently inhibits the interaction of ssDNA and GelRed, leading to a weak fluorescence intensity. The binding interaction between AA and ssDNA was confirmed by UV-Vis absorption spectrometry and fluorescence intensity. Under optimum conditions, the designed biosensor exhibited excellent linear response in range of 0.01-95 mM, moreover it showed high selectivity toward AA. The limit of detection was 0.003 mM. This biosensor was successfully applied for the determination of AA in water extract of potato fries and coffee in the range of 0.05-100 mM with LOD of 0.01 mM and 0.05-95 mM with LOD of 0.004 mM, respectively.

Targeted delivery of epirubicin to cancerous cell using copper sulphide nanoparticle coated with polyarginine and 5TR1 aptamer.

Chemotherapy has been widely acknowledged as a primary approach for cancer treatment. However, the administration of chemotherapy agents is often limited by their adverse effects that result from an inability to distinguish between healthy and malignant cells. As such, utilising nanocarriers in targeted drug delivery can significantly reduce these side effects while enhancing therapeutic efficacy. Herein, we developed copper sulphide nanoparticles (CuSNPs) loaded with epirubicin (Epi) coated by polyarginine and 5TR1 aptamer (CEPA) to target mucin-1 which is overexpressed on various types of cancer cells. MTT results revealed that CEPA significantly induced cytotoxicity of the drug in desired cell lines (C26 and MCF-7, mucin+) compared to CEPA-treated CHO cells (non-target, mucin-), verifying the targeting ability of CEPA complex. The obtained results from both flow cytometry analysis and cell imaging demonstrated that CEPA complex had successful internalisation in both target cell lines but no internalisation in CHO cell line. The result of in vivo assay showed more tumour inhibition and more accumulation in tumour tissue for CEPA complex in comparison to free Epi. To conclude, the CEPA complex has demonstrated superior efficacy and fewer adverse reactions compared to Epi. This indicates a promising and effective strategy for treating cancer.

Targeted delivery of doxorubicin and therapeutic FOXM1 aptamer to tumor cells using gold nanoparticles modified with AS1411 and ATP aptamers.

Objectives: A targeted delivery platform was prepared to co-deliver both doxorubicin (Dox) as an anticancer drug and FOXM1 aptamer as a therapeutic substance to breast cancer cells (4T1 and MCF-7) to reduce Dox side effects and increase its therapeutic efficacy. The targeted system (AuNPs-AFPA) consisted of FOXM1 aptamer, AS1411 aptamer (targeting oligonucleotide), ATP aptamer, and gold nanoparticles (AuNPs) as a carrier. Materials and Methods: AuNPs were synthesized by reduction of HAuCl4. Next, after pegylation of ATP aptamer, FOXM1 aptamer-PEGylated ATP aptamer conjugate (FPA) was prepared. Then, the AS1411 aptamer and FPA were exposed to the AuNPs surface through their thiol groups. Subsequently, Dox was loaded into the complex to form a targeted therapeutic complex. Results: The data of the MTT assay displayed that the targeted complex could remarkably reduce cell viability rate in target cells due to the overexpression of nucleolin on their cell membranes compared to nontarget cells, showing the targeting ability of AuNPs-AFPA-Dox. The in vivo antitumor effect confirmed that AuNPs-AFPA-Dox was capable of remarkably diminishing tumor growth relative to the free Dox in mice bearing 4T1 tumor cells. Conclusion: The results confirmed that the targeted system improved the therapeutic effect by loading high amounts of Dox alongside the presence of the therapeutic effect of FOXM1 aptamer. Finally, it can be concluded that AuNPs-AFPA-Dox by enhancing antitumor effectiveness and reducing toxicity toward non-target cells, can be used potentially as an effective strategy for the treatment of breast cancer.

Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery.

The formation of polymeric micelles in aqueous environments through the self-assembly of amphiphilic polymers can provide a versatile platform to increase the solubility and permeability of hydrophobic drugs and pave the way for their administration. In comparison to various self-assembly-based vehicles, polymeric micelles commonly have a smaller size, spherical morphology, and simpler scale up process. The use of polymer-based micelles for the encapsulation and carrying of therapeutics to the site of action triggered a line of research on the synthesis of various amphiphilic polymers in the past few decades. The extended knowledge on polymers includes biocompatible smart amphiphilic copolymers for the formation of micelles, therapeutics loading and response to external stimuli, micelles with a tunable drug release pattern, etc. Different strategies such as ring-opening polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain-transfer, nitroxide mediated polymerization, and a combination of these methods were employed to synthesize copolymers with diverse compositions and topologies with the proficiency of self-assembly into well-defined micellar structures. The current review provides a summary of the important polymerization techniques and recent achievements in the field of drug delivery using micellar systems. This review proposes new visions for the design and synthesis of innovative potent amphiphilic polymers in order to benefit from their application in drug delivery fields.

Aptamer-based targeted delivery systems for cancer treatment using DNA origami and DNA nanostructures.

Due to the limitations of conventional cancer treatment methods, nanomedicine has appeared as a promising alternative, allowing improved drug targeting and decreased drug toxicity. In the development of cancer nanomedicines, among various nanoparticles (NPs), DNA nanostructures are more attractive because of their precisely controllable size, shape, excellent biocompatibility, programmability, biodegradability, and facile functionalization. Aptamers are introduced as single-stranded RNA or DNA molecules with recognize their corresponding targets. So, incorporating aptamers into DNA nanostructures led to influential vehicles for bioimaging and biosensing as well as targeted cancer therapy. In this review, the recent developments in the application of aptamer-based DNA origami and DNA nanostructures in advanced cancer treatment have been highlighted. Some of the main methods of cancer treatment are classified as chemo-, gene-, photodynamic- and combined therapy. Finally, the opportunities and problems for targeted DNA aptamer-based nanocarriers for medicinal applications have also been discussed.

Dual-targeted delivery system using hollow silica nanoparticles with H+-triggered bubble generating characteristic coated with hyaluronic acid and AS1411 for cancer therapy.

OBJECTIVE: Herein, a dual-targeting delivery system using mesoporous silica nanoparticles with hollow structures (HMSNs) was developed for the specific delivery of epirubicin (EPI) to cancer cells and introducing a H+-triggered bubble generating nanosystem (BGNS). HMSNs containing EPI are covered by hyaluronic acid (HA) shell and AS1411 aptamer to create the BGNS-EPI-HA-Apt complex, which is highly selective against CD44 marker and nucleolin overexpressed on the surface of tumor cells. METHODS: MTT assay compared the cytotoxicity of different treatments in CHO (Chinese hamster ovary) cells as well as 4T1 (murine mammary carcinoma) and MCF-7 (human breast adenocarcinoma) cells. The internalization of Epi was assessed by flow cytometry along with fluorescence imaging. In vivo studies were conducted on BALB/c mice bearing a tumor from 4T1 cell line where monitoring included measuring tumor volume, mouse weight changes over time alongside mortality rate; accumulation levels for Epi within organs were also measured during this process. RESULTS: The collected data illustrated that BGNS-EPI-HA-Apt complex controlled the release of EPI in a sustained method. Afterward, receptor-mediated internalization via nucleolin and CD44 was verified in 4T1 and MCF-7 cells using fluorescence microscopy assay and flow cytometry analysis. The results of tumor inhibitory effect study exhibited that BGNS-EPI-HA-Apt complex decreased off-target effect and improved on-target effects because of its targeting ability. CONCLUSION: The data acquired substantiates that HA-surface modified HMSNs functionalized with aptamers possess significant potential as a focused platform for efficient transportation of anticancer agents to neoplastic tissues.

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

Label-free colorimetric sensor for Pb2+ determination using catalytic activity of MnO2 nanoflowers and elongated aptamer.

In this study, a label-free aptasensor utilizing colorimetric properties was developed to detect Pb2+ with high sensitivity. The approach involved applying modified aptamer which enhanced the oxidase-mimicking activity of MnO2 nanoflowers. This innovative method provides an efficient means for monitoring Pb2+ ions without requiring any labeling techniques. The fundamental principle of this aptasensor is based on the adsorption of a modified aptamer onto MnO2 nanoflowers' surface, which in turn increases their affinity for chromogenic substrates and enhances their catalytic activity. The proposed aptasensor exploits the high sensitivity due to the extension of the aptamer sequence length by terminal deoxynucleotidyl transferase (TdT). Under optimum experimental conditions, the developed colorimetric aptasensor indicated a linear detection range from 4 to 80 nM with a limit of detection (LOD) of 1.4 nM. Moreover, the aptasensor successfully monitored Pb2+ in the drinking water, milk and human serum samples. Henceforth, the colorimetric aptasensor exhibited in this study possesses several benefits such as uncomplicated operation, cost-effectiveness, label-free detection and remarkable sensitivity. Thus rendering it a suitable option for analyzing intricate samples.