Oligonucleotide based nanogels for cancer therapeutics.

Oligonucleotide-based nanogels, as nascent biomaterials, possess several unique functional, structural, and physicochemical features with excellent drug-loading capacity and high potential for cancer gene therapy. Ongoing studies utilizing oligonucleotide-based nanogels hold great promise, as these cutting-edge nanoplatforms can be elegantly developed with predesigned oligonucleotide sequences and complementary strands which are self-assembled or chemically crosslinked leading to the development of nanogels with predictable shape and tunable size with the desired functional properties. Current paper provides a summary of the properties, preparation methods, and applications of oligonucleotide-based nanogels in cancer therapy. The review is focused on both conventional and modified forms of oligonucleotide-based nanogels, including targeted nanogels, smart release nanogels (responsive to stimuli such as pH, temperature, and enzymes), as well as nanogels used for gene delivery. Their application in cancer immunotherapy and vaccination, photodynamic therapy, and diagnostic applications when combined with other nanoparticles is further discussed. Despite emerging designs in the development of oligonucleotide based nanogels, this field of study is still in its infancy, and clinical translation of these versatile nano-vehicles might face challenges. Hence, extensive research must be performed on in vivo behavior of such platforms determining their biodistribution, biological fate, and acute/subacute toxicity.

Biomolecules-Loading of 3D-Printed Alginate-Based Scaffolds for Cartilage Tissue Engineering Applications: A Review on Current Status and Future Prospective.

Osteoarthritis (OA) can arise from various factor including trauma, overuse, as well as degeneration resulting from age or disease. The specific treatment options will vary based on the severity of the condition, and the affected joints. Some common treatments for OA include lifestyle modifications, medications, physical therapy, surgery and tissue engineering (TE). For cartilage tissue engineering (CTE), three-dimension (3D) scaffolds are made of biocompatible natural polymers, which allow for the regeneration of new cartilage tissue. An ideal scaffold should possess biological and mechanical properties that closely resemble those of the cartilage tissue, and lead to improved functional of knee. These scaffolds are specifically engineered to serve as replacements for damaged and provide support to the knee joint. 3D-bioprinted scaffolds are made of biocompatible materials natural polymers, which allow for the regeneration of new cartilage. The utilization of 3D bioprinting method has emerged as a novel approach for fabricating scaffolds with optimal properties for CTE applications. This method enables the creation of scaffolds that closely mimic the native cartilage in terms of mechanical characteristics and biological functionality. Alginate, that has the capability to fabricate a cartilage replacement customized for each individual patient. This polymer exhibits hydrophilicity, biocompatibility, and biodegradability, along with shear-thinning properties. These unique properties enable Alginate to be utilized as a bio-ink for 3D bioprinting method. Furthermore, chondrogenesis is the complex process through which cartilage is formed via a series of cellular and molecular signaling. Signaling pathway is as a fundamental mechanism in cartilage formation, enhanced by the incorporation of biomolecules and growth factors that induce the differentiation of stem cells. Accordingly, ongoing review is focusing to promote of 3D bioprinting scaffolds through the utilization of advanced biomolecules-loading of Alginate-based that has the capability to fabricate a cartilage replacement tailored specifically to each patient's unique needs and anatomical requirements.

The crossroad of nanovesicles and oral delivery of insulin.

INTRODUCTION: Diabetes mellitus is one of the challenging health problems worldwide. Multiple daily subcutaneous injection of insulin causes poor compliance in patients. Development of efficient oral formulations to improve the quality of life of such patients has been an important goal in pharmaceutical industry. However, due to serious issues such as low bioavailability and instability, it has not been achieved yet. AREAS COVERED: Due to functional properties of the vesicles and the fact that hepatic-directed vesicles of insulin could reach the clinical phases, we focused on three main vesicular delivery systems for oral delivery of insulin: liposomes, niosomes, and polymersomes. Recent papers were thoroughly discussed to provide a broad overview of such oral delivery systems. EXPERT OPINION: Although conventional liposomes are unstable in the presence of bile salts, their further modifications such as surface coating could increase their stability in the GI tract. Bilosomes showed good flexibility and stability in GI fluids. Also, niosomes were stable, but they could not induce significant hypoglycemia in animal studies. Although polymersomes were effective, they are expensive and there are some issues about their safety and industrial scale-up. Also, we believe that other modifications such as addition of a targeting agent or surface coating of the vesicles could significantly increase the bioavailability of insulin-loaded vesicles.

Novel scaffold platforms for simultaneous induction osteogenesis and angiogenesis in bone tissue engineering: a cutting-edge approach.

Despite the recent advances in the development of bone graft substitutes, treatment of critical size bone defects continues to be a significant challenge, especially in the elderly population. A current approach to overcome this challenge involves the creation of bone-mimicking scaffolds that can simultaneously promote osteogenesis and angiogenesis. In this context, incorporating multiple bioactive agents like growth factors, genes, and small molecules into these scaffolds has emerged as a promising strategy. To incorporate such agents, researchers have developed scaffolds incorporating nanoparticles, including nanoparticulate carriers, inorganic nanoparticles, and exosomes. Current paper provides a summary of the latest advancements in using various bioactive agents, drugs, and cells to synergistically promote osteogenesis and angiogenesis in bone-mimetic scaffolds. It also discusses scaffold design properties aimed at maximizing the synergistic effects of osteogenesis and angiogenesis, various innovative fabrication strategies, and ongoing clinical studies.

Efficient CRISPR/Cas9-Mediated BAX Gene Ablation in CHO Cells To Impair Apoptosis and Enhance Recombinant Protein Production.

Background: Despite recent advances in recombinant biotherapeutics production using CHO cells, their productivity remains lower than industrial needs, mainly due to apoptosis. Objectives: Present study aimed to exploit CRISPR/Cas9 technology to specifically disrupt the BAX gene to attenuate apoptosis in recombinant Chinese hamster's ovary cells producing erythropoietin. Materials and Methods: The STRING database was used to identify the key pro-apoptotic genes to be modified by CRISPR/Cas9 technique. The single guide RNAs (sgRNAs) targeting identified gene (BAX) were designed, and CHO cells were then transfected with vectors. Afterward, changes in the expression of the Bax gene and consequent production rates of erythropoietin were investigated in manipulated cells, even in the presence of an apoptosis inducer agent, oleuropein. Results: BAX disruption significantly prolonged cell viability and increased proliferation rate in manipulated clones (152%, P-value = 0.0002). This strategy reduced the levels of Bax protein expression in manipulated cells by more than 4.3-fold (P-value <0.0001). The Bax-8 manipulated cells displayed higher threshold tolerance to the stress and consequence apoptosis compared to the control group. Also, they exhibited a higher IC50 compared to the control in the presence of oleuropein (5095 µM.ml-1 Vs. 2505 µM.ml-1). We found a significant increase in recombinant protein production levels in manipulated cells, even in the presence of 1,000 µM oleuropein compared to the control cell line (p-value=0.0002). Conclusions: CRISPR/Cas9 assisted BAX gene ablation is promising to improve erythropoietin production in CHO cells via engineering anti-apoptotic genes. Therefore, exploiting genome editing tools such as CRISPR/Cas9 has been proposed to develop host cells that result in a safe, feasible, and robust manufacturing operation with a yield that meets the industrial requirements.

Launching continuous kangaroo mother care through participatory action research in Iran.

BACKGROUND: This study describes the launching of a unit for continuous kangaroo mother care (KMC) in a teaching hospital (Taleghani) in Iran. METHODS: We used a participatory three-stage action research approach to establish a unit for continuous KMC: design (needs identification and planning for change); implementation (and reflection); and evaluation (and institutionalization). As part of the design and implementation stages, individual and focus group interviews were conducted with mothers, physicians, nurses, other healthcare personnel and policy makers. The evaluation was done by means of a standardized tool specifically developed for monitoring progress with the implementation of KMC. RESULTS: Four themes relating to potential barriers to implementation emerged from the analysis of the staff interviews, namely barriers associated with the mother, the father, the physician and the health system. Mothers' experiences of barriers were grouped into five themes: personal discomfort, fear, healthcare provider attitudes and actions, infrastructure constraints and family matters. An implementation progress score of 27.05 out of 30 was achieved, indicating that the continuous KMC unit was on the path to institutionalization. Some of the gaps identified related to policies on resource allocation, the discharge and follow-up system, and the transportation of infants in the KMC position. CONCLUSION: The study findings indicated that participatory action research is a suitable method for studying the establishment of a continuous KMC unit. When action research is practiced, there is a prospect of turning knowledge into action in the real world.

Prolonged local delivery of doxorubicin to cancer cells using lipid liquid crystalline system.

Exploring efficient strategies to eradicate the tumor tissue and enhance patient outcomes still remained a serious challenge. Systemic toxicity of the current chemotherapeutics and their low concentration in the tumor site limited reaching a practical approach in their administration and combinational therapy. Besides, complicated delivery platforms could not receive the marketing approval due to difficulties in scale up procedures. To this aim, we developed a simple injectable local delivery platform which provided a sufficient dose of the chemotherapeutic in the cancerous tissue with sustained release properties. Herein, various injectable in situ forming LLC formulations loaded with doxorubicin (DOX) were developed. Although there were many previous studies on lipid liquid crystal (LLC) based formulations, their performance as an injectable intratumoral depot system for local chemotherapy has not been extensively investigated yet. In the current study we developed 18 formulations of DOX loaded LLCs using Box-Behnken method via different ratios of phosphatidyl choline: sorbitan monooleate (PC: SMO), N-Methyl-2-pyrrolidone (NMP), and tween 80. The physicochemical properties of the formulations were investigated and their in vivo tumor inhibition efficiencies in C26 tumor bearing mouse model was further studied. The results indicated that DOX loaded PC: SMO/NMP/Tween 80 (50:50/50/2 w/w%) and DOX loaded PC: SMO/NMP (50:50/50 w/w%) formulations were syringeable with pseudoplastic behavior. Also, they could release the cargo in a sustained manner for 60 days. Compared to intravascular administration of DOX, intratumoral injection of the developed formulations led to a significant decrease in tumor volume and enhancement of the survival rate in murine tumor model. Additionally, animal imaging studies proved their prolonged accumulation in the tumor site. Histopathological studies showed that treatment with the DOX-loaded LLC formulations did not cause any systemic toxicity to vital organs. Taken together, we believe that the developed simple and efficient local delivery platform can be further used in combinational therapies and treatment of various solid tumors.

Hybrid in situ- forming injectable hydrogels for local cancer therapy.

Injectable in situ forming hydrogels are amongst the efficient local drug delivery systems for cancer therapy. Providing a 3D hydrogel network within the target tissue capable of sustained release of the chemotherapeutics made them attractive candidates for increasing the therapeutic index. Remarkable swelling properties, mechanical strength, biocompatibility, wide composition variety and tunable polymeric moieties have led to preparation of injectable hydrogels which also could be used as cavity adaptive chemotherapeutic-loaded implants to prevent post -surgical cancer recurrence. Implementation of various polymers, nanoparticles, peptide and proteins and different crosslinking chemistry facilitated the fabrication of hybrid hydrogels with favorable characteristics such as stimuli sensitive platforms or multifunctional systems. In the current review, we focused on design and fabrication strategies of injectable in situ forming hydrogels and summarized recent hybrid hydrogels used for local cancer therapy.

Recent advancements in nanoparticle-mediated approaches for restoration of multiple sclerosis.

Multiple Sclerosis (MS) is an autoimmune disease with complicated immunopathology which necessitates considering multifactorial aspects for its management. Nano-sized pharmaceutical carriers named nanoparticles (NPs) can support impressive management of disease not only in early detection and prognosis level but also in a therapeutic manner. The most prominent initiator of MS is the domination of cellular immunity to humoral immunity and increment of inflammatory cytokines. The administration of several platforms of NPs for MS management holds great promise so far. The efforts for MS management through in vitro and in vivo (experimental animal models) evaluations, pave a new way to a highly efficient therapeutic means and aiding its translation to the clinic in the near future.

Fabrication, characterization and in vitro cell exposure study of zein-chitosan nanoparticles for co-delivery of curcumin and berberine.

For the first time, we synthesized the co-delivery nanopolymers using zein protein as the core and chitosan polysaccharide as the shell to deliver curcumin (Cur) and berberine (Ber) in MDA-MB-231 breast cancer cells. It has been shown that Cur and Ber altogether have synergistic effects on multiple cancers. Herein, the curcumin-zein-berberine-chitosan (Cur-Z-Ber-Ch) nanoparticles were fabricated and their organization procedure was reported. Physicochemical properties of synthesized nanoparticles were determined by Fourier transform infrared (FTIR) spectroscopy, XRD and fluorescence spectroscopy analyses. The nanoparticles included relatively small particles (d = 168.24 nm) with +36.76 mV zeta potential. The resulting nanoparticles had high entrapment efficiency (about 75%) for Cur and 60% for Ber. The Cur-Z-Ber-Ch nanoparticles represented ideal redispersibility and storage stability after 4 months. Drug release of the freeze-dried nanoparticles had pH-sensitive characteristic. In vitro cytoxicity assay demonstrated that Cur-Z-Ber-Ch nanoparticles induced elevated cytotoxic effect in MDA-MB-231 and A549 cancer cells. In vitro studies in MDA-MB-231 cells demonstrated that the Cur-Z-Ber-Ch nanoparticles could successfully increase cellular uptake and apoptosis with significant inhibition of IL-8 pro-inflammatory cytokines in comparison to the free Cur + Ber bioactive molecules. These bio-nanoparticles are the co-delivery vehicle for Cur and Ber which could be beneficial for participating them into pharmaceutical products.

Implementation Barriers for Practicing Continuous Kangaroo Mother Care from the Perspective of Neonatologists and Nurses.

Introduction: Kangaroo mother care (KMC), as a complement to incubator care, is one of the ten recommendations of the World Health Organization (WHO) for the care of preterm infants. The KMC stabilizes the heart rate, improves oxygen saturation, makes weight gain better, and reduces crying in the infant. In order to launch KMC unit, the barriers for implementing this type of care should be recognized. Methods: This qualitative research was conducted using a focus group discussion and individual semi-structured interview with nurses, doctors, executive and management staff of a neonatal unit of a third level teaching hospital in Tabriz, northwest Iran. The participants were selected using purposeful sampling. Content analysis was used for analyzing data. Data were analyzed by MAXQDA 10 software. Results: After analyzing data, four main themes were extracted including mother-related barriers, father-related barriers, physician- related barriers, and system-related barriers. Conclusion: Based on the findings of the research, it seems that in order to facilitate practicing continuous KMC, much emphasis should be placed on training the parents and health care providers. Furthermore, in some cases, reforming the payment system for physicians, providing an instruction for performing continuous KMC, and continuous assessment of hospitals annually are necessary.

Possible Mechanisms and Special Clinical Considerations of Curcumin Supplementation in Patients with COVID-19.

The novel coronavirus outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized in late 2019 in Wuhan, China. Subsequently, the World Health Organization declared coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. The proportion of potentially fatal coronavirus infections may vary by location, age, and underlying risk factors. However, acute respiratory distress syndrome (ARDS) is the most frequent complication and leading cause of death in critically ill patients. Immunomodulatory and anti-inflammatory agents have received great attention as therapeutic strategies against COVID-19. Here, we review potential mechanisms and special clinical considerations of supplementation with curcumin as an anti-inflammatory and antioxidant compound in the setting of COVID-19 clinical research.

Implementation and effectiveness of continuous kangaroo mother care: a participatory action research protocol.

BACKGROUND: The efficacy of continuous kangaroo mother care (C-KMC) in reducing neonatal mortality and morbidity among low birthweight and premature infants has been confirmed. Despite the recommendations of the World Health Organization, UNICEF, and the Ministry of Health of Iran to use C-KMC for eligible hospitalized neonates, this type of care is not performed due to implementation problems. This protocol aims to describe the design, implementation, and assessment of C-KMC in one tertiary hospital by means of participatory action research. METHODS: The objective of this study is to design and implement a C-KMC program for neonates that will be performed in two phases using a stages-of-change model. The first phase will be conducted in three consecutive activities of designing, implementing, and assessing the introduction of C-KMC. The second phase of the study has a before-and-after design to assess the effectiveness of C-KMC by comparing the length of preterm neonates' stay in hospital and exclusive breastfeeding at discharge before and after implementing C-KMC. DISCUSSION: KMC is an important component of neonatal developmental care as part of family-centered care. Applying this type of care requires creating appropriate strategies, budget allocation, and clear and coordinated planning at different levels of the health system. The stages-of-change model is one of the appropriate approaches to the implementation of C-KMC.

Oral delivery of folate-targeted resveratrol-loaded nanoparticles for inflammatory bowel disease therapy in rats.

AIMS: In the current study, resveratrol-loaded PLGA nanoparticles targeted with folate were developed in order to protect resveratrol from fast degradation, modify its pharmacokinetics and increase its intestinal permeation. Then, the therapeutic efficacy of the prepared system was evaluated in suppression of colon inflammation on TNBS-induced colitis model. MAIN METHODS: In this regard, resveratrol was encapsulated in PLGA and FA-conjugated PLGA in order to prepare non-targeted (PLGA-RSV) and targeted (PLGA-FA-RSV) platforms, respectively. KEY FINDINGS: Obtained results demonstrated that the prepared formulations encapsulated the resveratrol with high encapsulation efficiency of 90.7% ± 5.1% for PLGA-RSV and 59.1% ± 3.3% for PLGA-FA-RSV. In vitro release experiment showed that the prepared formulations were capable of retaining good amount of resveratrol under the simulated gastric condition (HCl 0.1 N, pH 1.2), while significant amount of resveratrol was released under simulated intestinal condition (PBS, pH 7.4). The trans-well permeability rates through Caco-2 monolayer during 180 min, was determined to be 4.5%, 61% and 99% for resveratrol, PLGA-RSV and PLGA-FA-RSV respectively. The pathological analysis of the rat intestinal sections (hematoxylin & eosin staining) at 7th day post-TNBS colonic inflammation induction illustrated that the oral administrations of FA-PLGA-RSV and PLGA-RSV were able to significantly inhibit the inflammation and reduce neutrophil and lymphocytes accumulation. It is worth noting that the folate-targeted system demonstrated highest efficacy in suppressing colon inflammation. SIGNIFICANCE: It could be concluded that the encapsulation of resveratrol into biodegradable folate-targeted PLGA nanoparticles could introduce a potent platform in suppressing colonic inflammation thus offering a great capability for clinical translation.

Doxorubicin-loaded composite nanogels for cancer treatment.

Nanogels as a versatile vehicle for doxorubicin have attracted great attention during the last decade. Since a nanogel composite device transport encapsulated drugs to the site of action and release them in a desirable time-frame, it could provide higher therapeutic effect. By implementation of different polymers, polymer/inorganic NPs and various crosslinking chemistry, it is possible to fabricate novel composite nanogel systems with favorable characteristics such as smart intelligent systems or multipurpose platforms. Due to high stability, good drug loading capacity for hydrophobic and hydrophilic agents, nanogels introduce great opportunity in pharmaceutical innovations. Composite nanogels show capability in gene, drug and diagnostic agents' delivery while providing an ideal platform for theranostic purposes as multifunctional systems. Doxorubicin as an anticancer agent is widely used against numerous cancers. Due to high systemic toxicity of doxorubicin, there is still need for its safe and specific delivery to the site of action. In this regard, so many efforts have been put in by the researchers for preparation of different nanogel formulations of doxorubicin in order to produce more efficient formulations. This review focuses on design, fabrication, advantages and disadvantages of composite nanogel-based doxorubicin formulations.

Prophylactic Chemotherapy with Methotrexate Leucovorin in High-Risk Hydatidiform Mole.

AIM: Gestational Trophoblastic Neoplasia (GTN) is used to describe a group of malignant gestational tumors originating from the placenta. The chance of having malignant GTN is high in a high-risk molar pregnancy. The main aim of this study is to investigate the effectiveness of using prophylactic chemotherapy in high-risk molar pregnancy to prevent malignant GTN. METHOD: In this case-control retrospective study, all patients with high-risk mole referred to Firoozgar and Akbarabadi Hospitals affiliated with Iran University of Medical Sciences (IUMS) from 2003 to 2013 were divided into two groups of recipient and non-recipient of methotrexate prophylactic chemotherapy.Demographic information including age, parity, weight, serum ßHCG before and after the intervention, level of liver function tests (LFT) and GTN were analyzed. RESULTS: There were 102 patients with a mean age of 27.13 years (SD= 0.37), and 51 patients (50 %) received prophylactic Methotrexate (MTX), and others were the non-receivers. Finally, 23 patients (22.5%) were inflicted with GTN, and 79 (77.5 %) did not. The average time of ßHCG spontaneous remission between the groups were 2.5 (SD=1.33) and 3.2 (SD=1.21), for the recipient and non-recipient, respectively, which showed a significant difference (p). CONCLUSION: This study concludes that prophylactic chemotherapy with MTX and leucovorin may be capable of reducing GTN, which supports the prescription of MTX in high-risk mole, especially in countries with limited resources. The toxicity of methotrexate can be reduced with the addition of leucovorin.
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Prevalence and Risk Factors of Urinary/Anal Incontinence and Pelvic Organ Prolapse in Healthy Middle-Aged Iranian Women.

OBJECTIVES: Urinary incontinence (UI) and anal incontinence (AI) cause concern, social exclusion, and ultimately reduced quality of life in women. The aim of present study was to assess the prevalence and related risk factors of UI, AI, and pelvic organ prolapse (POP). METHODS: The present study recruited 340 menopausal women living in Tabriz in northwest Iran. The data collection tools included the Pelvic Floor Distress Inventory-20 and a personal and social information questionnaire. POP was diagnosed via clinical examination using the simplified pelvic organ prolapse quantification system. RESULTS: The prevalence of UI and POP was approximately 50%, and approximately 16% of participants reported AI. Based on the odds ratios, the most remarkable risk factor of urinary stress incontinence was the number of vaginal deliveries, whereas that of urinary urge incontinence was obesity. Episiotomy and age were the most major risk factors of AI and POP, respectively. CONCLUSIONS: The results of the present study showed that the prevalence of POP, UI, and AI is remarkably high among postmenopausal women, warranting the need to prioritize the assessment of POP and various incontinences in middle-aged women in the primary health care system. Furthermore, increased emphasis should be put on modifiable risk factors.

Improvement of ethanol production from birch and spruce pretreated with 1-H-3-methylmorpholinium chloride

Background: Pretreatment is the critically important step for the production of ethanol from lignocelluloses. In this study, hardwood birch (Betula pendula) and softwood spruce (Norway spruce) woods were pretreated with a newly synthesized morpholinium ionic liquid, 1-H-3-methylmorpholinium chloride ([HMMorph][Cl]), followed by enzymatic hydrolysis and fermentation to ethanol. Results: [HMMorph][Cl] was synthesized using inexpensive raw materials, i.e., hydrochloric acid and N-methyl morpholine, following a simple process. The influence of pretreatment time (2, 3, 5, and 8 h) and temperature (120 and 140°C) in terms of hydrolysis efficiency was investigated. Glucose yields from enzymatic hydrolysis were improved from 13.7% to 45.7% and 12.9% to 51.8% after pretreatment of birch and spruce woods, respectively, under optimum pretreatment conditions (i.e., at 140°C for 3 h) as compared to those from pristine woods. Moreover, the yields of ethanol production from birch and spruce were increased to 34.8% and 44.2%, respectively, while the yields were negligible for untreated woods. Conclusions: This study demonstrated the ability of [HMMorph][Cl] as an inexpensive agent to pretreat both softwood and hardwood.

Fabrication of acetylated carboxymethylcellulose coated hollow mesoporous silica hybrid nanoparticles for nucleolin targeted delivery to colon adenocarcinoma.

To efficiently deliver the chemotherapeutics to the tumor tissue and minimize the associated adverse effects, nucleolin targeted hybrid nanostructure based on hollow mesoporous silica nanoparticles (HMSNs) were fabricated. To provide the controlled, sustained drug release and enhance blood circulation, the surface of doxorubicin-encapsulated HMSNs were coated with acetylated carboxymethyl cellulose (Ac-CMC) and then covalently conjugated to AS1411 aptamer for guided drug delivery to nucleolin overexpressed cancerous cells. In vitro cellular uptake and cytotoxicity studies confirmed that AS1411 aptamer specifically targets nucleolin overexpressing MCF-7 and C26 cells. Moreover, the in vivo tumor inhibitory effect of AS1411 aptamer conjugated formulation demonstrated a superior therapeutic efficiency over non-targeted formulation and free doxorubicin. The current study might open a new insight to the development of targeted intelligent hybrid materials based on AcCMC-coated HMSNs with high loading capacity, smart characteristics and desirable anticancer potential.

Curcumin-entrapped MUC-1 aptamer targeted dendrimer-gold hybrid nanostructure as a theranostic system for colon adenocarcinoma.

Gold NPs have great potential in biomedical applications. PAMAM dendrimers are spherical, hyper branched macromolecules which can encapsulate therapeutic molecules while stabilizing metal nanoparticle such as gold NPs. The aim of the current study was to investigate the theranostic capability of curcumin-loaded dendrimer-gold hybrid structure. Dendrimer-gold hybrid structure was synthesized by complexing AuCl4- ions with PEGylated amine-terminated generation 5 poly (amidoamine) dendrimer. The resultant hybrid system was loaded with curcumin. The curcumin-loaded PEGylated Au dendrimer was further conjugated to MUC-1 aptamer in order to target the colorectal adenocarcinoma in vitro and in vivo. Obtained results demonstrated that the targeted theranostic agent was accumulated in HT29 and C26 cells in vitro and showed higher cellular cytotoxicity in comparison with non-targeted system. On the other hand, in vivo experiment demonstrated the potential of targeted theranostic system in CT-scan tumor imaging as well as cancer therapy. Findings from this study suggested that MUC-1 targeted curcumin-loaded PEGylated Au dendrimers have good X-ray attenuation and is desirable probe for CT imaging while demonstrating high therapeutic index against colorectal cancer adenocarcinoma.