Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off-the-shelf versatile tumor delivery vehicle.

Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

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.

Emotion-focused therapy for women with premenstrual dysphoric disorder: a randomized clinical controlled trial.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a debilitating condition, affecting women of reproductive age. It is characterized by severe periodic physical and psychological symptoms, which end after the onset of menstruation. This study aimed to evaluate the effectiveness of emotion-focused therapy (EFT) for PMDD patients. METHODS: A total of 48 PMDD women, in the age range of 18-44 years, were randomly assigned to two intervention and control groups. The intervention group participated in 16 weeks of EFT treatment, while the control group was selected based on the waiting list (waitlist control group) and followed-up after three months. Forty-four patients finally completed this study. The participants completed the Premenstrual Syndrome Screening Tool (PSST), Difficulties in Emotion Regulation Scale (DERS), and Depression Anxiety Stress Scale-21 (DASS-21) in the first premenstrual period before treatment, the first premenstrual period after treatment, and the premenstrual period three months after treatment. RESULTS: Based on the repeated measure analysis of variances, the total score of DERS and the total score of PSST decreased significantly (P < 0.05). Also, in DASS-21, the scores of depression and stress subscales reduced significantly (P < 0.05), while there was no significant decrease in the score of anxiety subscale (P > 0.05). CONCLUSION: Based on the present results, EFT can be an effective treatment for alleviating the symptoms of PMDD. This treatment can reduce the emotion regulation difficulties of women with PMDD and alleviate the symptoms of depression and stress. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT ID: IRCT20220920055998N1, Registered on: 12/2/2023.

Room Temperature Exciton-Polariton Condensation in Silicon Metasurfaces Emerging from Bound States in the Continuum.

We show the first experimental demonstration of room-temperature exciton-polariton (EP) condensation from a bound state in the continuum (BIC). This demonstration is achieved by strongly coupling stable excitons in an organic perylene dye with the extremely long-lived BIC in a dielectric metasurface of silicon nanoparticles. The long lifetime of the BIC, mainly due to the suppression of radiation leakage, allows for EP thermalization to the ground state before decaying. This property results in a condensation threshold of less than 5 µJ cm-2, 1 order of magnitude lower than the lasing threshold reported in similar systems in the weak coupling limit.

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.

A simple tag-free fluorometric aptasensing assay for sensitive detection of kanamycin.

A novel label-free and enzyme-free fluorescence aptasensing assay that uses Sybr Green I (SGI) as the signal indicator for the kanamycin determination was designed. An aptamer-complementary strand (Apt/CP) conjugate was formed, which provided the intercalation sites for SGI and, therefore, a considerable fluorescent signal. The introduction of the target led to the separation of Apt from CP due to the high affinity of Apt toward kanamycin. Hence, the suitable intercalation gaps reduced, which resulted in a decrease in the generated fluorescent signal. Under optimized conditions, a broad linear concentration range from 0.05 µM to 20 µM and a limit of detection of 11.76 nM were obtained, confirming the ability of the fabricated aptasensor for sensitive and specific kanamycin detection in real samples such as milk and human serum. The aptasensing method has the potential to be extensively employed in the food industry and veterinary science due to its simplicity, sensitivity, user-friendly, and capability of on-site detection of kanamycin.

Robust tag-free aptasensor for monitoring of tobramycin: Architecting of rolling circle amplification and fluorescence synergism.

With the unpredictable risks on human health and ecological safety, tobramycin (TOB) as an extensively applied antibiotic has embraced global concern. Herein, a label-free fluorescent aptasensor was developed that opened up an innovative sensing strategy for monitoring trace TOB levels. Based on the rolling circle amplification (RCA) process, a giant DNA building was established by the catalytic action of T4 DNA ligase and Phi 29 DNA polymerase with the cooperation of the specific aptamer as a primer skeleton. By having the role of signal amplifier template, the RCA product with the G-quadruplex sequence duplications was decorated by a high number of the thioflavin T (ThT) fluorescent dyes. The aptasensor with good selectivity toward TOB achieved a detection limit as low as 150 pM. Thanks to its accurate target quantification, ease of operation, economic manufacture, as well as high potency for real-time and point-of-care testing, the represented aptasensor is superb for clinical application and food safety control.

A fluorescent aptasensor for quantification of cocaine mediated by signal amplification characteristics of UiO-66/AuNPs nanocomposite.

Due to the detrimental effects of cocaine on the human body such as organ damage, paranoia, immunodeficiency, cardiovascular disease, blood pressure, and stress, it is highly required to develop sensing approaches for its rapid and facile determination. Based on the signal enhancement capability of the UiO-66/AuNPs nanocomposite and acting as a capture agent, we designed a cost-effective fluorescent aptasensor for cocaine detection. The cocaine presence in the sample would cause a considerable escalation in the quenching of the fluorescence signal. The aptasensor achieved the linear response range over 0.5 µM-20 µM with a low detection limit of 0.178 µM. The selectivity of the designed aptasensing assay was successfully confirmed by examining several analgesic drugs. The aptasensor was employed for cocaine determination in human serum as the real samples. This method has a substantial benefit the for development of a low-cost and facile tool in medicine and forensic science.

Time-resolved Fluorescence DNA-based Sensors for Reducing Background Fluorescence of Environment.

The fluorescence assay is one of the popular methods that is applied for detection of different targets. However, this method may show low sensitivity and high background in biological samples due to the natural fluorescence of different compounds in complicated samples. In addition, it inevitably affects the detection results accuracy. A fundamental solution to this problem is the use of the time-resolved fluorescence technique (TRF). The main component of this technique is the use of long fluorescence lifetime reagents. In this review, various time-resolved fluorescent reagents such as complexes of lanthanide ions, lanthanide-doped inorganic nanoparticles; Mn-doped ZnS quantum dots (QDs) and pyrene excimer are introduced. Moreover, TRF sensors, especially TRF aptasensors (DNA-based sensors) are discussed. This review will give new ideas for researchers to develop novel high-sensitive TRF sensors that can remove or decrease background fluorescence and use them for the detection of various targets in complicated samples without treatment.

Targeted poly(L-glutamic acid)-based hybrid peptosomes co-loaded with doxorubicin and USPIONs as a theranostic platform for metastatic breast cancer.

Peptosomes, as a vesicular polypeptide-based system and a versatile carrier for co-delivery of hydrophilic and hydrophobic materials, provide great delivery opportunities due to the intrinsic biocompatibility and biodegradability of the polypeptides backbone. In the current study, a novel poly(L-glutamic acid)-block-polylactic acid di-block copolymer (PGA-PLA) was synthesized in two steps. Firstly, γ-benzyl L-glutamate-N-carboxy anhydride (BLG-NCA) and 3,6-dimethyl-1,4-dioxane-2,5-dione were polymerized using N-hexylamine and benzyl alcohol as initiators to produce poly(γ-benzyl L-glutamate (PBLG) and polylactic acid. Then, PBLG was deprotected to produce PGA. Secondly, PGA was conjugated to the benzyl-PLGA to fabricate PGA-PLA diblock copolymer. The synthesized diblock copolymer was used for the encapsulation of doxorubicin, as hydrophilic anticancer and ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) as hydrophobic contrast agent within aqueous core and bilayer of vesicular peptosome, respectively via double emulsion method. The prepared peptosomes (Pep@USPIONs-DOX) controlled the release of DOX (<15 % of the encapsulated DOX release up to 240 h of incubation at the physiological conditions) while increasing the stability and solubility of the hydrophobic USPIONs. Then, AS1411 DNA aptamer was decorated on the surface of the PGA-PLA peptosomes (Apt-Pep@USPIONs-DOX). The prepared targeted and non-targeted platforms showed spherical morphology with hydrodynamic sizes of 265 ± 52 and 229 ± 44 nm respectively. In vitro cellular cytotoxicity and cellular uptake were studied in nucleolin positive (4T1) and nucleolin negative (CHO) cell lines. Cellular uptake of the targeted formulation was greater than that of non-targeted peptosome, while cellular internalization of these peptosomes was identical in CHO cells. Moreover, targeted peptosomes showed greater toxicity than non-targeted peptosome in 4T1 cell line. The prepared theranostic targeted peptosomes demonstrated improved capability in terms of survival rate, biodistribution, tumor suppression efficiency, and MR imaging in the 4T1 tumor-bearing mice.

Targeted delivery of epirubicin to breast cancer cells using poly-aptamer DNA nanocarriers prepared by the RCA method with multiple repeats of aptamers of FOXM1 and AS1411.

OBJECTIVE: We evaluated the DNA nanocarriers synthesized by rolling circle amplification (RCA), composed of multiple repeats of AS1411 and FOXM1 aptamers for targeted epirubicin delivery to breast cancer cells. METHODS: Agarose gel electrophoresis and scanning electron microscopy were used to nanostructure characterizing. Drug loading and drug release were determined by fluorometry. Cytotoxicity comparison by MTT assay was applied among epirubicin, nanoparticle, and complex (nanoparticle carrying epirubicin) in L929 (normal murine fibroblast) and 4T1 (murine mammary carcinoma) cells. Cellular epirubicin internalization was assessed by flow cytometry and fluorescence imaging. In vivo studies in 4T1 tumor-bearing BALB/c mice were conducted by monitoring tumor volume, mouse weight, and mortality rate and measuring the accumulated epirubicin in organs. RESULTS: The negatively charged nanoparticles were under 200 nm and stable. Fifty microliters of 6 µM epirubicin was loaded in 50 µL nanoparticle. Epirubicin release at acidic pH was more. Complex compared with epirubicin, had more entry and cytotoxicity in target cells (p value ≤.01), higher therapeutic effect (p value ≤.001), and tumor drug accumulation. CONCLUSION: The poly-aptamer nanocarriers have the characteristics of being safe, stable, efficient epirubicin loading, pH-dependent drug release, and tumor-targeting ability in vitro and in vivo.

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.

Fabrication of anionic dextran-coated micelles for aptamer targeted delivery of camptothecin and survivin-shRNA to colon adenocarcinoma.

In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.

Targeted Delivery Platforms for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative condition of the central nervous system (CNS) that presents with varying levels of disability in patients, displaying the significance of timely and effective management of this complication. Though several treatments have been developed to protect nerves, comprehensive improvement of MS is still considered an essential bottleneck. Therefore, the development of innovative treatment methods for MS is one of the core research areas. In this regard, nanoscale platforms can offer practical and ideal approaches to the diagnosis and treatment of various diseases, especially immunological disorders such as MS, to improve the effectiveness of conventional therapies. It should be noted that there is significant progress in the development of neuroprotective strategies through the implementation of various nanoparticles, monoclonal antibodies, peptides, and aptamers. In this study, we summarize different particle systems as well as targeted therapies, such as antibodies, peptides, nucleic acids, and engineered cells for the treatment of MS, and discuss their potential in the treatment of MS in the preclinical and clinical stages. Future advances in targeted delivery of medical supplies may offer new strategies for complete recovery as well as practical treatment of progressive forms of MS.

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

BACKGROUND: Cancer 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. RESULTS: In 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. CONCLUSION: In this regard, the synthesized theranostic peptosomes offer innovative hybrid multipurpose platform for fighting against breast cancer.

Design and assessment of novel synthetic peptides to inhibit quorum sensing-dependent biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most common biofilm-producing bacteria, often leading to long-term and chronic infections. The LasR regulator protein acts as the central regulator of the quorum sensing (QS) system and coordinates the expression of some virulence and biofilm genes. In this study, novel peptides (WSF, FASK, YDVD) were designed for binding to the domain of the transcriptional activator of the LasR protein and interfere with LasR in the QS system of P. aeruginosa. The effects of these peptides on biofilm production, expression of biofilm-related genes (AlgC, PslA, PelA), and growth of planktonic P. aeruginosa were investigated. All three peptides inhibited the growth of P. aeruginosa planktonic cells at 1600 µg ml-1 and exhibited anti-biofilm effects at sub-inhibitory concentrations (800 µg ml-1). Measurements of the mRNA levels of biofilm-related genes at sub-inhibitory concentrations of the designed peptides showed a significant decrease.

PNA-ATP aptamer-capped doxorubicin-loaded silica nanoparticles for targeted cancer therapy.

Nanomaterial-based drug delivery has opened new horizons in cancer therapy. This study aimed to investigate the in vitro and in vivo anti-cancer effects of a hyaluronic acid (HA)-targeted nanocarrier based on hollow silica nanoparticles (HSNPs), gated with peptide nucleic acid (PNA) and ATP aptamer (ATPApt) and loaded with doxorubicin (DOX). After formulation of a smart drug delivery nanosystem (HSNPs/DOX/ATPApt/PNA/HA), drug release, cytotoxicity, uptake, and in vivo anti-tumor properties were studied. Drug release test showed the controlled release of encapsulated DOX in response to ATP content. MTT and flow cytometry indicated that HA could improve both cytotoxicity and cellular uptake of the formulation. Moreover, HA-targeted formulation enhanced both the survival rate and tumor inhibition in the tumor-bearing mice compared with free DOX (P < 0.05). Our findings confirmed that HA-targeted nanoformulation, gated with PNA/aptamer and loaded with DOX can provide a novel therapeutic platform with great potential for cancer therapy.

Fabrication of deferasirox-decorated aptamer-targeted superparamagnetic iron oxide nanoparticles (SPION) as a therapeutic and magnetic resonance imaging agent in cancer therapy.

In the current study, the synthesis of a theranostic platform composed of superparamagnetic iron oxide nanoparticles (SPION)-deferasirox conjugates targeted with AS1411 DNA aptamer was reported. In this regard, SPION was amine-functionalized by (3-aminopropyl)trimethoxysilane (ATPMS), and then deferasirox was covalently conjugated onto its surface. Finally, to provide guided drug delivery to cancerous tissue, AS1411 aptamer was conjugated to the complex of SPION-deferasirox. The cellular toxicity assay on CHO, C-26 and AGS cell lines verified higher cellular toxicity of targeted complex in comparison with non-targeted one. The evaluation of in vivo tumor growth inhibitory effect in C26 tumor-bearing mice illustrated that the aptamer-targeted complex significantly enhanced the therapeutic outcome in comparison with both non-targeted complex and free drug. The diagnostic capability of the prepared platform was also evaluated implementing C26-tumor-bearing mice. Obtained data confirmed higher tumor accumulation and higher tumor residence time for targeted complex through MRI imaging due to the existence of SPION as a contrast agent in the core of the prepared complex. The prepared multimodal theranostic system provides a safe and effective platform for fighting against cancer.

Application of the catalytic activity of gold nanoparticles for development of optical aptasensors.

Biosensor technology is considered to be a great alternative in analytical techniques over the conventional methods. Among many recently developed techniques and devices, aptasensors are interesting because of their high specificity, selectivity and sensitivity. Combining aptamer as a biological recognition element with gold nanoparticles (AuNPs) as probe, are becoming more general owing to their beneficial properties, including low cost and ability to analyze specific targets on-site and using naked eye. Hydrogen bonds, nucleic acid hybridization, aptamer-target and antigen-antibody binding, Raman signature, enzyme inhibition, and enzyme-mimicking activity are main different sensing strategies exploited in AuNPs-based optical aptasensors. In this review article, we discussed the recent advances in optical aptasensors with a special emphasis on the catalytic activity property of AuNPs.

PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.

Prostate cancer (PCa) is one of the most prevalent non-drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self-assembled based on PEG-PLA nanoparticles (PEG-PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate-specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti-proliferation of drugs-loaded PEG-PLA NPs and ACUPA-PEG-PLA against LNCaP (PSMA+ ) and PC3 (PSMA- ) cells. PEG-PLA NPs with an average size of 130-140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA-modified PEG-PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA-conjugated PEG-PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer-targeting PSMA that suffer from short circulation half-life and limited therapeutic efficacy.