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Accumulative structure or cluster-like shape is one of the important features of social networks. These structures and clusters are communities in a complex network and are fully detectable. Common group behaviors of different communities can be categorized using community detection methods. Categorize behavior allows the study of each part of the network to be done centrally. This paper uses trust-based centrality to detect the communities that make up the network. Centrality determines the relative importance of a node in the graph of social networks. Redefining the trust-based centrality makes it possible to change the position in the analysis of centrality and separates the local central nodes and global central nodes. Then, a trust-based algorithm is proposed to express the strength of trust penetration conceptually between nodes to extract communities in networks. This method has led to the achievement of a flexible and effective community detection method. The proposed algorithm is applied to four benchmark networks. The experiments consist of two independent parts. The first part is to use the proposed algorithm to detect clusters and communities. After that, the algorithm is compared with a Girvan–Newman inspired method. The second part is the implementation of the proposed algorithm with a large number of iterations with the aim of modularity maximization and comparing it with other community detection algorithms. Although, the modularity criterion has been used to validate and compare the solution quality in both independent parts of the experiments. The results show about 1.4–5.2% improvement in community detection.

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.

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.

Hybrid vesicular systems (lipopolymersomes) are promising platforms for minimizing the liposomes and polymersomes disadvantages in terms of chemotherapeutic transportation. In this regard, lipopolymersome has been designed to integrate the advantage of both polymersomes and liposomes to enable better structural integrity of the bilayer after encapsulation of hydrophobic drugs while maintaining the soft nature of liposomes, superior serum stability, and high encapsulation efficiency of cargos in the bilayer segment. In the present study, we reported preparation and characterization of five camptothecin (CPT)-loaded lipopolymersomal formulations composed of poly (ethylene glycol)–poly (lactic acid) (PEG-PLA) and dipalmitoylphosphatidylcholine (DPPC) at different molar ratios using film rehydration method. Afterward, the preferred formulation was tagged with AS1411 DNA aptamer in order to evaluate the therapeutic index using nucleolin-positive colon cancer cell lines (HT29 and C26). The obtained data indicated that the prepared CPT-loaded lipopolymersome at a PEG-PLA: DPPC ratio of 75:25 exhibited superior stability and high loading capacity compared to other systems. Moreover, high cytotoxicity of the aptamer-targeted lipopolymersome and increased tumor accumulation were observed in comparison with non-targeted one. The designed polymer-rich lipopolymersomal platform offers bright future for the development of potent nanomedicine against cancer.

Nanoscale porphyrinic metal−organic frameworks have emerged as promising therapeutic system for photodynamic therapy (PDT) of cancer in recent years. Nevertheless, their low selectivity towards malignant tissues is a hindrance for highly efficient cancer photodynamic therapy. In this study, a nano metal-organic framework ([CuL-[AlOH]2]n (Cu MOF), with Cu (II) core, as a PDT active center, was coated with red blood cell (RBC) membrane after loaded with doxorubicin (DOX), to avoid immediate clearance from the bloodstream and persist for longer periods of time in circulation. Then, a carboxylic acid-end aptamer (MUC1) was decorated on the RBC-coated DOX-loaded MOF (Apt-RBC-MOF@DOX) in order to provide targeted chemo and photodynamic therapy. The MTT and flow cytometry experiments exhibited that Apt-RBC-MOF@DOX provided highly efficient DOX transportation and toxicity against 4T1 and MCF7 breast cancer cells in vitro in comparison to non-targeted RBC-MOF@DOX. On the other hand, the single dose intravenous injection of Apt-RBC-MOF@DOX considerably reduced the tumor growth in vivo. The desirable biodistribution, faster liver clearance, and higher tumor accumulation were confirmed by ex vivo fluorescent imaging. Moreover, under irradiation at 630 nm, the fabricated nanostructures exhibited effective synergistic chemo and photodynamic therapy, proved via in vitro MTT assay and tumor ablation in vivo. The developed Apt-RBC-MOF@DOX could serve as a potent platform in clinic for targeted chemo-photodynamic dual therapy.

Recent technological approaches in drug delivery have attracted scientist interest for improving therapeutic index of medicines and drug compliance. One of the powerful strategies to control the transportation of drugs is implementation of intelligent stimuli-responsive drug delivery system (DDS). In this regard, tumor tissues with unique characteristics including leaky vasculature and diverse enzyme expression profiles facilitate the development of efficient enzyme-responsive nanoscale delivery systems. Based on the stimuli nature (physical, chemical and biological), these systems can be categorized into three groups according to the nature of trigger initiating the drug release. Enzymes are substantial constituents of the biotechnology toolbox offering promising capabilities and ideal characteristics to accelerate chemical reactions. Nanoparticles which have the ability to trigger their cargo release in the presence of specific enzymes are fabricated implementing fascinating physico-chemical properties of different materials in a nanoscale dimension. In order to reduce the adverse effects of the therapeutic agents, nanocarriers can be utilized and modified with enzyme-labile linkages to provide on-demand enzyme-responsive drug release. In the current review, we give an overview of drug delivery systems which can deliver drugs to the tumor microenvironment and initiate the drug release in response to specific enzymes highly expressed in particular tumor tissues. This strategy offers a versatile platform for intelligent drug release at the site of action.

In the current study, in order to augment the therapeutic efficacy of curcumin, thermo-sensitive biodegradable hydrogel composed of poly (e-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (e-caprolactone-co-lactide) (PCLA-PEG-PCLA) incorporating curcumin-loaded polyethylene glycol-b-polylactide (mPEG-PLA) nanopolymersome was prepared. The final objective of this study was to introduce a biodegradable thermo-responsive, injectable hydrogel that can prolong and localize therapeutic effects of curcumin. The obtained results demonstrated that the encapsulation of curcumin nanopolymersome in the thermos-sensitive hydrogel provided the sustained controlled release of the encapsulated curcumin. The rheological investigation demonstrated that the viscosity of the prepared composite hydrogel (20% copolymer solution) was low which made it intratumorally injectable. However, at physiological temperature (37 °C), system was in gel state with good mechanical strength thereby providing sustained release of the encapsulated platform upon intratumoral administration. In vivo administration of the prepared composite hydrogel incorporating curcumin nanopolymersome to ectopic C6 glioma tumor model in nude mice illustrated ideal therapeutic response of the prepared composite platform. The key innovation of the current study was the development of biodegradable, injectable therapeutic-loaded implant to improve the outcomes of glioma treatment while reducing the treatment complications.

In the current study, polyethylene glycol (PEG) was linked to polylactide (PLA) through the synthetic peptide PVGLIG which can be selectively cleaved by the tumor-associated matrix metalloproteinase 2 (MMP-2) enzyme. The synthesized chimeric triblock polymer of PEG-b-PVGLIG-PLA was implemented to form nanoscale self-assemble chimeric polymersomes. The hydrophobic SN38 was loaded into polymersomes with 70.3% ± 3.0% encapsulation efficiency demonstrating monodispersed spherical morphologies with 172 ± 30 nm dimension. The prepared chimeric polymersomal formulation provided controlled release of SN38 at physiological condition while illustrating seven-folds higher release rate when exposed to MMP-2 enzyme. At the next stage, AS1411 aptamer was conjugated onto the surface of MMP-2 responsive polymersomal formulation in order to provide guided drug delivery against nucleolin positive cells. In vitro cellular toxicity assay against C26 cell line (nucleolin positive) demonstrated significantly higher toxicity of targeted formulation in comparison with non-targeted one in low SN38 concentrations (0.15–1.25 μg/mL). In vivo study in mice bearing subcutaneous C26 tumor showed higher therapeutic index for MMP-2 responsive chimeric polymersomal formulation of SN38 in comparison with non-responsive one. On the other hand, AS1411 aptamer-targeted MMP-2 responsive chimeric polymersomal formulation exhibited highest therapeutic index compared to other groups. It could be concluded that the targeted chimeric polymersomes bearing both cleavable peptide sequence between their blocks and targeting ligand on their surface, provide favorable characteristics as an ideal delivery system against cancer.