Delivery Platform Research Articles

Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles.

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid-based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV-based nucleic acid delivery systems and is a leap forward to clinical EV applications.

Application of galactosylated albumin for targeted delivery of triptolide to suppress hepatocellular carcinoma progression through inhibiting de novo lipogenesis

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis.

Enhanced Targeted Drug Delivery for Scar Prevention: Clathrin‐Coated Solid Lipid Nanoparticles for Model Drug Encapsulation

AbstractExcessive scar formation is a major complication of wound healing. Premature release of anti‐scarring drugs can negatively impact healing. This study aims to develop a targeted delivery system for the controlled release of anti‐scarring drugs during the scar formation stage. Solid lipid nanoparticles (SLNs) coated with Clathrin, a cage‐like protein, to prevent premature drug release is developed. Insulin‐like growth factor (IGF) is conjugated to the SLNs for targeted delivery via its affinity for connective tissue growth factor (CTGF), a protein overexpressed during scar formation. The IGF‐Clathrin‐SLNs exhibited a size of 300 ± 20 nm and a zeta potential of 9.23 ± 0.4 mV. In vitro studies demonstrated sustained release of the encapsulated drug‐ kynurenic acid; less than 10% of kynurenic acid is released within three days, while over 50% is released within 10 h upon Clathrin removal using a surfactant at pH 8. Cellular uptake studies confirmed targeting efficacy. Fibroblasts with low CTGF expression displayed low uptake (<10%), whereas MCF7 cells with high CTGF expression showed significantly higher uptake (80%). This work demonstrates a promising targeted delivery platform for the controlled release of anti‐scarring drugs during scar formation.

Comparing Email Versus Text Messaging as Delivery Platforms for Supporting Patients With Major Depressive Disorder: Noninferiority Randomized Controlled Trial.

The prevalence of major depressive disorder (MDD) poses significant global health challenges, with available treatments often insufficient in achieving remission for many patients. Digital health technologies, such as SMS text messaging-based cognitive behavioral therapy, offer accessible alternatives but may not reach all individuals. Email communication presents a secure avenue for health communication, yet its effectiveness compared to SMS text messaging in providing mental health support for patients with MDD remains uncertain. This study aims to compare the efficacy of email versus SMS text messaging as delivery platforms for supporting patients with MDD, addressing a critical gap in understanding optimal digital interventions for mental health care. A randomized noninferiority pilot trial was conducted, comparing outcomes for patients receiving 6-week daily supportive messages via email with those receiving messages via SMS text message. This duration corresponds to a minimum of 180 days of message delivery. The supportive messages maintained consistent length and structure across both delivery methods. Participants (N=66) were recruited from the Access 24/7 clinic in Edmonton, Alberta, among those who were diagnosed with MDD. The outcomes were measured at baseline and 6 months after enrollment using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the World Health Organization Well-Being Index (WHO-5). Most of the participants were females (n=43, 65%), aged between 26 and 40 years (n=34, 55%), had high school education (n=35, 58%), employed (n=33, 50%), and single (n=24, 36%). Again, most participants had had no history of any major physical illness (n=56, 85%) and (n=61, 92%) responded "No" to having a history of admission for treatment of mood disorders. There was no statistically significant difference in the mean changes in PHQ-9, GAD-7, and WHO-5 scores between the email and SMS text messaging groups (mean difference, 95% CI: -1.90, 95% CI -6.53 to 2.74; 5.78, 95% CI -1.94 to 13.50; and 11.85, 95% CI -3.81 to 27.51), respectively. Both supportive modalities showed potential in reducing depressive symptoms and improving quality of life. The study's findings suggest that both email and SMS text messaging interventions have equivalent effectiveness in reducing depression symptoms among individuals with MDD. As digital technology continues to evolve, harnessing the power of multiple digital platforms for mental health interventions can significantly contribute to bridging the existing treatment gaps and improving the overall well-being of individuals with depressive conditions. Further research is needed with a larger sample size to confirm and expand upon these findings. ClinicalTrials.gov NCT04638231; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552095/.

Suspension Bead Loading (SBL): An Economical Protein Delivery Platform to Study URM1's Behavior in Live Cells.

Uniquely modified synthetic proteins are difficult to produce in large quantities, which could limit their use in various in vitro settings and in cellular studies. In this study, we developed a method named "suspension bead loading" (SBL), to deliver protein molecules into suspended living cells using glass beads, which significantly reduces the amount of protein required for effective delivery. We investigated the delivery efficiency of functionally different proteins and evaluated the cytotoxic effect of our method and the chemical and functional integrity of the delivered protein. We utilized SBL to address questions related to ubiquitin-related modifier 1 (URM1). Employing minimal protein quantities, SBL has enabled us to study its behavior within live cells under different redox conditions, including subcellular localization and conjugation patterns. We demonstrate that oxidative stress alters both the localization and conjugation pattern of URM1 in cells, highlighting its possible role in cellular response to such extreme conditions.

Photothermal and Antibacterial PDA@Ag/SerMA Microneedles for Promoting Diabetic Wound Repair.

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

Biodegradable Polymeric Nanoparticle-Based Drug Delivery Systems: Comprehensive Overview, Perspectives and Challenges.

In the last few decades, there has been a growing interest in the use of biodegradable polymeric nanoparticles (BPNPs) as the carriers for various therapeutic agents in drug delivery systems. BPNPs have the potential to improve the efficacy of numerous active agents by facilitating targeted delivery to a desired site in the body. Biodegradable polymers are especially promising nanocarriers for therapeutic substances characterized by poor solubility, instability, rapid metabolism, and rapid system elimination. Such molecules can be efficiently encapsulated and subsequently released from nanoparticles, which greatly improves their stability and bioavailability. Biopolymers seem to be the most suitable candidates to be used as the nanocarriers in various delivery platforms, especially due to their biocompatibility and biodegradability. Other unique properties of the polymeric nanocarriers include low cost, flexibility, stability, minimal side effects, low toxicity, good entrapment potential, and long-term and controlled drug release. An overview summarizing the research results from the last years in the field of the successful fabrication of BPNPs loaded with various therapeutic agents is provided. The possible challenges involving nanoparticle stability under physiological conditions and the possibility of scaling up production while maintaining quality, as well as the future possibilities of employing BPNPs, are also reviewed.

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord.

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord.

Strengthening the effectiveness of community health system: Assessing the factors that enhance or constrain the delivery of health services within communities in Nigeria

IntroductionSub-optimal community health service delivery (CHSD) has been a challenge constraining community health systems (CHS) globally, especially in developing countries such as Nigeria. This paper examined the key factors that either enhance or constrain CHSD in Nigeria at the individual, community/facility and governmental levels while recommending evidence-based solutions for sustaining and improving CHSD within the framework of CHS.MethodsData were collected through a qualitative study undertaken in three states (Anambra, Akwa-Ibom and Kano) in Nigeria. Respondents were formal/informal health providers, community leaders and representatives of civil society organizations all purposively sampled. There were 90 in-depth interviews and 12 focus group discussions, which were audio-recorded, transcribed verbatim and analysed thematically using codes to identify key themes.ResultsFactors constraining community health service delivery at the individual level were poor health-seeking behaviour, preference for quacks and male dominance of service delivery; at the community/facility level were superstitious/cultural beliefs and poor attitude of facility workers; at the governmental level were inadequate financial support, embezzlement of funds and inadequate social amenities. Conversely, the enabling factors at the individual level were community members’ participation and the compassionate attitude of informal providers. At the community and facility levels, the factors that enhanced service delivery were synergy between formal and informal providers and support from community-based organizations and structures. At the governmental level, the enhancing factors were the government’s support of community-based formal/informal providers and a clear line of communication.ConclusionsCommunity health service delivery through a functional community-health system can improve overall health systems strengthening and lead to improved community health. Policy-makers should integrate community health service delivery in all program implementation and ultimately work with the community health system as a veritable platform for effective community health service delivery.

Mucoadhesive in situ nasal gel of amoxicillin trihydrate for improved local delivery: Ex vivo mucosal permeation and retention studies

Orally administered amoxicillin is recommended as the first-line treatment of acute bacterial rhinosinusitis (ABR) and given in a high-dose regimen. However, the risk of various systemic adverse reactions and low oral bioavailability are unbearable, increasing the threat of antibiotic resistance. Therefore, nasal delivery of amoxicillin can be a potential approach for effectively treating ABR locally, as well as overcoming those drawbacks. In a way to guarantee the effectiveness for local therapy in nasal cavity, the permeation and retention properties are of significant importance considerations. Accordingly, the present work aimed to investigate the characteristics with respect to the nasal applicability of the in situ gelling amoxicillin trihydrate (AMT) and further evaluate its permeability and retention properties through human nasal mucosa. The lyophilized formulations were characterized utilizing the Differential Scanning Calorimetry (DSC) and X-ray Powder Diffraction (XRPD), and also evaluated for its polarity, reconstitution time, droplet size distribution, mucoadhesive properties, and ex vivo permeability and retention studies. The results confirmed that the in situ gelling AMT formulations possess adequate mucoadhesive behavior, especially the formulation containing 0.3 % of gellan gum. Substantially, the in situ gelling AMT formulations were able to retain the drug on the surface of nasal mucosa instead of permeating across the membrane; thus, suitable for treating nasal infections locally. Altogether, the in situ gelling systems demonstrates promising abilities as a delivery platform to enhance local application of AMT within the nasal cavity.

Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression

This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or β-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.

Exosomal Delivery Enhances the Antiproliferative Effects of Acid-Hydrolyzed Apiaceae Spice Extracts in Breast Cancer Cells.

Breast cancer remains a leading cause of death worldwide. The Apiaceae plant family includes many culinary spices that have been shown to have medicinal properties. Many phytochemicals exhibit potent bioactivities but often suffer from poor uptake and oral bioavailability. Bovine milk and colostrum exosomes are a compelling drug delivery platform that could address this issue; these natural nanoparticles can be loaded with hydrophilic and lipophilic small molecules and biologics, resulting in lower doses needed to inhibit cancer growth. Ethanolic extracts of eight Apiaceae spices were examined for phytochemical content and antiproliferative potential. Acid hydrolysis (AH) was employed to remove glycosides, asses its impacts on extract efficacy, and evaluate its effects on exosome loading and subsequent formulation efficacy. Antiproliferative activity was assessed through MTT assays on T-47D, MDA-MB-231, and BT-474 breast cancer cells; all extracts exhibited broad antiproliferative activity. AH enhanced the bioactivity of cumin, caraway, and fennel in T-47D cells. Celery, cumin, anise, and ajwain showed the highest activity and were assayed in exosomal formulations, which resulted in reduced doses required to inhibit cellular proliferation for all extracts except AH-cumin. Apiaceae spice extracts demonstrated antiproliferative activities that can be improved with AH and further enhanced with exosomal delivery.

Uncovering merchants’ willingness to wait in on-demand food delivery markets

While traditional on-demand food delivery services help restaurants reach more customers and enable doorstep deliveries, they also come with drawbacks, such as high commission fees and limited control over the delivery process. White-label food delivery services have emerged as an alternative, ready-to-use platform for restaurants to arrange delivery for customer orders received through their applications or websites, without the constraints imposed by traditional on-demand food delivery platforms or the need to develop an in-house delivery operation. Although several studies have investigated consumer behavior when using traditional on-demand food delivery services, there is limited research on merchants’ behavior when adopting white-label food delivery services. In this research, we develop a non-parametric survival model to estimate merchants’ willingness to wait when using white-label food delivery services and examine how various factors, such as delivery fees, the number of placed orders, and average waiting time, affect merchants’ willingness to wait, drawing on a dataset of both delivered and canceled orders from a crowd-sourcing delivery platform in Singapore. The empirical results show that merchants’ willingness to wait has a non-linear relationship with their average waiting time; it initially increases and then decreases with average waiting time. Moreover, the relationship between merchants’ willingness to wait during the pick-up stage and their average waiting times in the matching stage follows a similar non-linear trend. Merchants who have experienced lengthy waiting times on average in the matching stage tend to be less patient in the pick-up stage. This research sheds light on the stage-specific dynamics of merchants waiting behavior in white-label delivery service and provides insights for delivery platforms to optimize their operational strategies and enhance user experiences.

“All in one” lipid-polymer nanodelivery system for gene therapy of ischemic diseases

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy

Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach–Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a “central-to-peripheral” drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Encapsulation of human natural killer cells into novel gelatin-based polymeric hydrogel networks.

In the innate immune system, natural killer (NK) cells are effector lymphocytes which control several tumor types and microbial infections by limiting disease spread and tissue damage. With tumor cell killing abilities, with no priming or prior activation, NKs are potential anti-cancer therapies. In clinical practice, NKs are used in intravenous injections as they typically grow as suspension, similar to other blood cells. In this study, we designed a novel and effective biomaterial-based platform for NK cell delivery, which included in-situ NK cell encapsulation into three-dimensional (3D) biocompatible polymeric scaffolds for potential anti-cancer treatments. Depending on physical cross-linking between an alginate (ALG) polymer and a divalent cation, two natural polymers (gelatin (GEL) and hyaluronic acid (HA)) penetrated into pores and generated an inter-penetrating hydrogel system with improved mechanical properties and stability. After extensive characterization of hydrogels, NK cells were encapsulated inside using our in-situ gelation procedure to provide a biomimetic microenvironment.&#xD.

Microchip Based Isolation and Drug Delivery of Patient-Derived Extracellular Vesicles Against Their Homologous Tumor.

Extracellular vesicles (EVs) have demonstrated significant potential in drug delivery and anti-tumor therapy. Despite this promising strategy, challenges such as specific targeting, EVs purification persist. In this study, a personalized nanodrug delivery platform using patient-derived tumor EVs (PT-EVs) based on a microchip is presented. The microchip integrates multiple functions, including capture, enrichment, drug loading, and elution of PT-EVs. The isolation and drug-carrying procedures are completed within a 12 h timeframe, achieving a recovery rate of 65%, significantly surpassing the conventional ultracentrifuge (UC) method. Furthermore, PT-EVs derived from patient tumor models are first utilized as natural drug carriers, capitalizing on their inherent homing ability to precisely target homologous tumors. Lenvatinib and doxorubicin (DOX), two commonly utilized drugs in the clinical treatment of hepatocellular carcinoma (HCC), are loaded into PT-EVs and delivered to a matched in vitro tumor model that recapitulates original tumors for drug susceptibility testing. As is proven, PT-EVs exhibit robust tumor cell targeting and efficient receptor-mediated cellular uptake, and the efficacy of chemotherapeutic drugs is improved significantly. These results suggest that this platform could be a valuable tool for efficient isolation of PT-EVs and personalized drug customization, particularly when working with limited clinical samples, thus supporting personalized and precision medicine.

Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation is proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel is proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protects BMSCs from shear force and mechanical stress before and after injection, but also repairs the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD.

Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

AbstractMaterials with engineered nano‐scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, evidence is present that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo‐cytoplasmic barrier, and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through the Endosomal Sorting Complexes Required for Transport (ESCRT)‐mediated mechanisms. The findings suggest a potential for nano\topographic materials to temporarily breach the nuclear membrane with potential applications in direct nuclear sensing and delivery.

In vitro study of a new theranostic smart niosomal nanostructure for direct delivery of docetaxel via anti-PSMA aptamer

In this study, a novel quantum dot (QD)-labeled specific anti-prostate-specific membrane antigen (PSMA) aptamer sequence was conjugated to a pH-responsive niosomal particle platform for delivery of docetaxel (DTX) components. The target cells were overexpressed PSMA. This strategy can minimize the systemic toxicity prevalent in DTX. Synthesis of pH-responsive niosomes was achieved by using thin-film hydration. The conjugation of the aptamer A10 to the niosomal particle was done via a disulfide bond. Furthermore, CdSe/ZnS QDs were fabricated using a hot-injection process, then were functionalized with mercapto propanoic acid (MPA) ligands and attached to the 3’ terminal of aptamer via an Amide bind. Moreover, several characterization analyses including dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were performed. Additionally, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and apoptosis assays, as well as fluorescence microscopy, were used to assess the performance of the fabricated system. The data revealed a homogenous round-shaped population of niosomes with an average size of 200 nm and a negative surface charge was synthesized successfully. The FTIR and XRD evaluations confirmed the fabrication of both QDs and niosomes and the bioconjugation processes. The drug release happened in a controlled manner with a pH-sensitivity feature. The cellular uptake of aptamer-conjugated particles enhanced and consequently caused more cytotoxicity of prostate cancer cells with overexpression of PSMA. Furthermore, the QDs provided an ability to trace the treatment and its uptake via the targeted tissue. Overall, this study contributed to the development of a low-risk, highly specific platform for the delivery of both therapeutics and imaging agents.