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.

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.

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 targeting of Mg/N doped-carbon quantum dots with folic and hyaluronic acid for targeted drug delivery and cell imaging.

Mg/N doped-carbon quantum dots (CQDs) with dual drug targeting and cell imaging properties was synthesized. Mg/N doped-CQDs synthesized by a hydrothermal method. Operating pyrolysis parameters such as temperature, time, and pH were optimized to achieve CQDs with high quantum yield (QY). This CQD applied in cellular imaging. For the first time, dual active targeting of Mg/N doped CQDs performed using folic acid and hyaluronic acid (CQD-FA-HA). Then, epirubicin (EPI) loaded on this nanocarrier as the final complex (CQD-FA-HA-EPI). Cytotoxicity analysis, cellular uptake, and cell photography performed for the complex on three cell lines, including 4T1, MCF-7, and CHO. In vivo studies were performed in BALB/c inbred female mice models bearing breast cancer. Characterization results showed the successful formation of Mg/N doped-CQDs with a high QY of 89.44%. In vitro drug release approved pH dependency of synthesized nanocarrier with a controlled release behavior. Cytotoxicity tests and cellular uptake results demonstrated increased toxicity and absorption into 4T1 and MCF-7 cell lines for targeted nanoparticles compared to free drug. In cell imaging, an increase in the entry of the complex into 4T1 and MCF-7 cells compared to free drug, confirmed the proper function of the synthesized complex. In vivo results indicated that the tumor volume of mice receiving CQD-FA-HA-EPI was the lowest among other studied groups, along with the lowest damage to the liver, spleen, and heart according to the histopathological analysis. Finally, CQD-FA-HA proposed as a novel platform with tumor targeting, drug carrier, and photoluminescence properties.

A multi-storey DNA nanostructure containing doxorubicin and AS1411 aptamer for targeting breast cancer cells.

Herein, we presented a novel DOX-loaded multi-storey DNA nanostructure, including AS1411 aptamer as a targeting agent for treatment of target cells (MCF-7 and 4T1). Gel retardation test and fluorometric analysis were used to examine the construction of DNA nanostructure and loading of DOX in the complex. At pH 5.5 and 7.4, the release patterns of DOX from the prepared formulation were studied. Cell viability test was conducted to analyse the cell cytotoxicity ability of the DOX loaded multi-storey DNA nanostructure compared to free DOX in 4T1, MCF-7 (target) and CHO cells (non-target). Flow cytometry analysis was used to examine the DOX-loaded DNA nanostructure internalisation. Finally, the developed DOX-loaded multi-storey DNA nanostructure was tested in vivo to see if it could prevent tumour growth. The drug was released from the nanocomplex in a pH-related process (higher release in acidic pH compared to neutral pH). According to MTT assay, DOX-loaded DNA nanostructure damaged nucleolin positive cells while not significantly affecting nucleolin negative cells. The formulation was efficaciously internalised into target cells (4T1 and MCF-7), but not into non-target ones. Moreover, DOX-loaded DNA nanostructure can restrict tumour growth, increase survival rate, and accumulate significantly more in the tumour site than free DOX.

Design and synthesis of a star-like polymeric micelle modified with AS1411 aptamer for targeted delivery of camptothecin for cancer therapy.

Improving of tumor targeting and decreasing side effects at normal cells of antitumor drugs are necessary to promote the cancer chemotherapy efficacy. Herein, we have synthesized a novel 21-arm star like diblock polymer of ß-cyclodextrin-{poly(ε-caprolactone)-poly(2-aminoethylmethacrylate)}21 which decorated with nucleolin aptamer (AS1411). The diblock polymer was prepared by combined ROP with electron transfer atom transfer radical polymerization (ARGET ATRP) methods followed camptothecin (CPT) encapsulation with high entrapment efficiency (65%). Subsequently, the attachment of AS1411 aptamer via covalent bond led to the formation of the final product ß-CD-(PCL-PAEMA)21/AS1411/CPT. In vitro drug release experiment demonstrated almost 50% of CPT was released in 72 h at acidic tumoral environment. The data of cellular toxicity (MTT) showed that the final product remarkably enhanced cell death in MCF-7 and 4T1 cells while normal cells (L929) showed high viability toward the prepared complex. Also, the finding of flow cytometry analysis and fluorescence imaging indicated successful internalization of complex into the target cells but not the nontarget cells. The in vivo experiments revealed the fact that ß-CD-(PCL-PAEMA)21/AS1411/CPT micelles showed high tumor inhibitory potential in comparison with free CPT. These findings exhibited the excellent ability of the novel star-like polymeric micelle with targeting agent for the targeted and effective delivery of CPT in cancer treatment.

Recent achievements and advances in optical and electrochemical aptasensing detection of ATP based on quantum dots.

The design and fabrication of high sensitive and selective biosensing platforms areessential goals to precisely recognize biomaterials in biological assays. In particular, determination of adenosine triphosphate (ATP) as the main energy currency of the cells and one of the most important biomolecules in living organisms is a pressing need in advanced biological detection. Recently, aptamer-based biosensors are introduced as a new direct strategy in which the aptamers (Apts) directly bind to the different targets and detect them on the basis of conformational changes and physical interactions. They can also be conjugated to optical and electronic probes such as quantum dot (QD) nanomaterials and provide unique QD aptasensing platforms. Currently, these Apt-based biosensors with excellent recognition features have attracted extensive attention due to the high specificity, rapid response and facile construction. Therefore, in this review article, recent achievements and advances in aptasensing detection of ATP based on different detection methods and types of QDs are discussed. In this regard, the optical and electrochemical aptasensors have been categorized based on detection methods; fluorescence (FL), electrochemiluminescence (ECL) and photoelectrochemical (PEC) and they have been also divided to two main groups based on QDs; metal-based (M-based) and carbon-based (C-based) materials. Then, their advantages and limitations have been highlighted, compared and discussed in detail.