Nucleolin-targeted doxorubicin and ICG co-loaded theranostic lipopolymersome for photothermal-chemotherapy of melanoma in vitro and in vivo.

Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and CT-scan imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ±â€¯6 and 74 ±â€¯5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma.

Targeted doxorubicin-loaded core-shell copper peroxide-mesoporous silica nanoparticles for combination of ferroptosis and chemotherapy of metastatic breast cancer.

In the current study, a tumor microenvironment responsive (TME-responsive) copper peroxide-mesoporous silica core-shell structure with H2O2 self-supplying ability was fabricated for targeted ferroptosis/chemotherapy against metastatic breast cancer. At the first stage, copper peroxide nanodot was synthesized and subsequently coated with mesoporous organosilica shell. After (3-Aminopropyl) triethoxysilane (APTMS) functionalization of the organosilica shell, doxorubicin (DOX) was loaded in the mesoporous structure of the nanoparticles and then, heterofunctional COOH-PEG-Maleimide was decorated on the surface through EDC/NHS chemistry. Afterward, thiol-functionalized AS1411 aptamer was conjugated to the maleimide groups of the PEGylated nanoparticles. In vitro study illustrated ROS generation of the system in the treated 4 T1 cell. Cellular uptake and cytotoxicity experiments showed enhanced internalization and cytotoxicity of the targeted system comparing to non-targeted one. The in vivo study on ectopic 4 T1 tumor induced in Female BALB/c mice showed ideal therapeutic effect of Apt-PEG-Silica-DOT@DOX with approximately 90 % tumor suppression in comparison with 50 % and 25 % tumor suppression for PEG-Silica-DOT@DOX and PEG-Silica-DOT. Moreover, Apt-PEG-Silica-DOT@DOX provide favorable characteristics for biosafety issues concerning the rate of survival and loss of body weight. The prepared platform could serve as a multifunctional system with smart behavior in drug release, tumor accumulation and capable for ferroptosis/chemotherapy against breast cancer.

Targeted delivery of SN38 to breast cancer using amphiphilic diblock copolymers PHPMA-b-PBAEM as micellar carriers with AS1411 aptamer.

Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38.

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.

Synthesis of folate targeted theranostic cubosomal platform for co-delivery of bismuth oxide and doxorubicin to melanoma in vitro and in vivo.

Liquid crystalline nanoparticles (LCNPs) have gained much attention in cancer nanomedicines due to their unique features such as high surface area, storage stability, and sustained-release profile. In the current study, a novel LCNP for co-encapsulation of Bi2O3 and hydrophilic doxorubicin (DOX) was fabricated and functionalized with folic acid (FA) to achieve efficient tumor targeting toward CT-scan imaging and chemotherapy of melanoma in vitro and in vivo. LCNPs Bi2O3 NPs were prepared using glycerol monooleate-pluronic F-127 (GMO/PF127/water). Firstly, GMO/water were homogenized to prepare LC gel. Then, the stabilizer aqueous solution (PF127/Bi2O3/DOX) was added to the prepared LC gel and homogenized using homogenization and ultrasonication. The formulated NPs exhibited superior stability with encapsulation efficiency. High cytotoxicity and cellular internalization of the FA-Bi2O3-DOX-NPs were observed in comparison with Bi2O3-DOX-NPs and the free DOX in folate-receptor (FR) overexpressing cells (B16F10) in vitro. Moreover, ideal tumor suppression with increased survival rate were observed in tumorized mice treated with FA-Bi2O3-DOX-NPs compared to those treated with non-targeted one. On the other hand, the CT-imaging ability of the Bi2O3-DOX-NPs was tested inB16F10 tumor-bearing mice. The obtained data indicated a high potential of the developed targeted theranostic FA-Bi2O3-DOX-NPs for diagnostics and treatment of melanoma.

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.

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.

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.

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.

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.

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.

Signaling crosstalk between mesenchymal stem cells and tumor cells: Implications for tumor suppression or progression.

Mesenchymal stem cells (MSCs) have been extensively used in various therapeutic applications over the last two decades, particularly in regenerative medicine and cancer treatment. MSCs have the ability to differentiate into mesodermal and non-mesodermal lineages, which makes them a popular choice in tissue engineering and regenerative medicine. Studies have shown that MSCs have inherent tumor-suppressive properties and can affect the behavior of multiple cells contributing to tumor development. Additionally, MSCs possess a tumor tropism property and have a hypoimmune nature. The intrinsic features of MSCs along with their potential to undergo genetic manipulation and be loaded with various anticancer therapeutics have motivated researchers to use them in different cancer therapy approaches without considering their complex dynamic biological aspects. However, despite their desirable features, several reports have shown that MSCs possess tumor-supportive properties. These contradictory results signify the sophisticated nature of MSCs and warn against the potential therapeutic applications of MSCs. Therefore, researchers should meticulously consider the biological properties of MSCs in preclinical and clinical studies to avoid any undesirable outcomes. This manuscript reviews preclinical studies on MSCs and cancer from the last two decades, discusses how MSC properties affect tumor progression and explains the mechanisms behind tumor suppressive and supportive functions. It also highlights critical cellular pathways that could be targeted in future studies to improve the safety and effectiveness of MSC-based therapies for cancer treatment. The insights obtained from this study will pave the way for further clinical research on MSCs and development of more effective cancer treatments.

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.

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.

Bioengineering strategies to enhance the interleukin-18 bioactivity in the modern toolbox of cancer immunotherapy.

Cytokines are the first modern immunotherapeutic agents used for activation immunotherapy. Interleukin-18 (IL-18) has emerged as a potent anticancer immunostimulatory cytokine over the past three decades. IL-18, structurally is a stable protein with very low toxicity at biological doses. IL-18 promotes the process of antigen presentation and also enhances innate and acquired immune responses. It can induce the production of proinflammatory cytokines and increase tumor infiltration of effector immune cells to revert the immunosuppressive milieu of tumors. Furthermore, IL-18 can reduce tumorigenesis, suppress tumor angiogenesis, and induce tumor cell apoptosis. These characteristics present IL-18 as a promising option for cancer immunotherapy. Although several preclinical studies have reported the immunotherapeutic potential of IL-18, clinical trials using it as a monotherapy agent have reported disappointing results. These results may be due to some biological characteristics of IL-18. Several bioengineering approaches have been successfully used to correct its defects as a bioadjuvant. Currently, the challenge with this anticancer immunotherapeutic agent is mainly how to use its capabilities in a rational combinatorial therapy for clinical applications. The present study discussed the strengths and weaknesses of IL-18 as an immunotherapeutic agent, followed by comprehensive review of various promising bioengineering approaches that have been used to overcome its disadvantages. Finally, this study highlights the promising application of IL-18 in modern combinatorial therapies, such as chemotherapy, immune checkpoint blockade therapy, cell-based immunotherapy and cancer vaccines to guide future studies, circumventing the barriers to administration of IL-18 for clinical applications, and bring it to fruition as a potent immunotherapy agent in cancer treatment.

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.

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.

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-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.