Delivery Of Agents Research Articles

Peptide Based Quantum Dots Conjugates as Promising Theranostic Candidates in Nanomedicines: Applications in Drug Delivery and Bioimaging

AbstractAdvancement in nanotechnology paves new way in nanomedicine via synthesis of various scaffolds bearing multifunctionalities having characteristics of both as diagnostic and therapeutic applications. Quantum dots (QDs) with exceptional luminescent properties exhibited some unbeatable characteristics of small size with ease in surface modifications and thus make them suitable candidates to be used in drug delivery and diagnosis of diseases. Meanwhile, various type of peptides are known in literature for their excellent therapeutic properties and thus make them promising candidates to be used as conjugate partner with the QDs. Highly luminescent properties and surface modifications flexibility of QDs, further urge to use them as promising conjugate partner with many small molecules including peptides and thus found applications in the field of nanomedicines. Thus Peptides ‐QDs conjugates exhibited the properties of both QDs and bioactivity, biocompatibility features of peptides and hence leave behind the limitation of both the individual partners (i. e. QDs and peptides). Thus the combined Peptides‐QDs conjugates acts as theranostic agent for various diseases where these acts as both imaging and drug delivery agent. Hence the present review focused on the theranostic applications of the Peptides‐QDs conjugates in various area of the nanomedicines. Also we focus on the area of improvement and advancement in nanomedicines for the diagnosis and treatment of the diseases in the early stages.

Green Urban

Green Urban is a sustainable waste management system offering a shopping section where users can buy daily items focused on pollution prevention and plastic alternatives. Users can sell scrap metal and other recyclable products for a fair price or receive purchase discounts, and they can pre-order pickup dates. Sewage and kitchen waste collection are offered as part of a fully automated subscription plan. To encourage purchases and usage, users earn reward points. The system includes a delivery agent module and a delivery boy module to facilitate the transportation of goods to warehouses and scrapyards, ensuring efficient waste management and recycling processes

Perceived impacts of a school-based growth mindset programme ‘Mindset Teams’ in Scotland: a qualitative study

BackgroundTeachers as delivery agents within school-based mindset programmes is a potential intervention strategy for improving pupils’ outcomes. The Mindset Teams programme, utilises teachers as delivery agents, with an aim to improve learning resilience for health and attainment outcomes among schools in Scotland. This study examined the perceived impacts of the programme to develop a programme theory of change and refine an earlier co-produced logic model.MethodsAcross six intervention schools, one-to-one interviews were conducted with teachers (N = 18) and focus groups were conducted with 23 pupils aged 8-11-years. Fourteen stakeholders involved in programme provision, secondary school delivery, funding decisions or policy-related areas also participated in a one-to-one interview. Qualitative data were analysed using thematic analysis with a combined deductive and inductive coding approach.ResultsThemes were identified in relation to impacts on teachers (five themes), pupils (eight themes), and broader outcomes (two themes), with most themes discussed by teachers and wider stakeholders. Across data, findings highlighted the proposed mechanisms by which the programme was intending to produce impacts, largely through increasing teacher knowledge and facilitating a positive school environment. Themes demonstrated the breadth of perceived programme impacts, highlighting both attainment and wellbeing outcomes among pupils.ConclusionsFindings provide support for Mindset programmes focusing on the development of teachers’ mindsets, highlighting the resultant perceived impacts this can have on both teachers and pupils alike. Future research should seek to capture health and wellbeing measures alongside attainment data to fully explore programme impacts.

Targeted Inhibition of Lymphovascular Invasion Formation with CREKA Peptide-Modified Silicasomes to Boost Chemotherapy in Bladder Cancer.

Despite its significant clinical efficacy as a first-line treatment for advanced bladder cancer, cisplatin-based chemotherapy provides a limited benefit for patients with lymphovascular invasion (LVI), which is characterized by the presence of tumor emboli within blood vessels and associated with enhanced cisplatin resistance and metastatic potential. Notably, platelets, a critical component of LVI, hinder the delivery of chemotherapeutic agents to tumors and facilitate metastasis. Consequently, platelet function inhibition holds the potential to disrupt LVI formation, as well as augment the antitumor activity of cisplatin. Herein, we developed a tumor microenvironment-targeted nanodrug with lipid-coated mesoporous silica nanoparticles (silicasomes) that synergistically combines cisplatin with an antiplatelet agent, tirofiban, for bladder cancer treatment. The customized nanodrug can concurrently prevent LVI formation and enhance the chemotherapeutic efficacy without significant adverse effects. This study supports the integration of chemotherapy and antiplatelet therapy via a silicasome-based nanosystem as a highly promising strategy for bladder cancer management.

Enhanced Efficacy of Gastric Cancer Treatment through Targeted Exosome Delivery of 17-DMAG Anticancer Agent.

In this study, we explored the potential of genetically engineered exosomes as vehicles for precise drug delivery in gastric cancer therapy. A novel antitumor strategy using biocompatible exosomes (Ex) was devised by genetically engineering adipose-derived stem cells to express an MKN45-binding peptide (DE532) on their surfaces. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) was encapsulated in engineered exosomes, resulting in 17-DMAG-loaded DE532 exosomes. In both in vitro and in vivo experiments using mouse gastric cancer xenograft models, we demonstrated that 17-DMAG-loaded DE532 Ex exhibited superior targetability over DE532 Ex, 17-DMAG-loaded Ex, and Ex. Administration of the 17-DMAG-loaded DE532 Ex yielded remarkable antitumor effects, as evidenced by the smallest tumor size, lowest tumor growth rate, and lowest excised tumor weight. Further mechanistic examinations revealed that the 17-DMAG-loaded DE532 Ex induced the highest upregulation of the pro-apoptotic marker B-cell lymphoma-2-like protein 11 and the lowest downregulation of the anti-apoptotic marker B-cell lymphoma-extra large. Concurrently, the 17-DMAG-loaded DE532 Ex demonstrated the lowest suppression of antioxidant enzymes, such as superoxide dismutase 2 and catalase, within tumor tissues. These findings underscore the potential of 17-DMAG-loaded DE532 exosomes as a potent therapeutic strategy for gastric cancer, characterized by precise targetability and the potential to minimize adverse effects.

Macrocycle-Based Supramolecular Drug Delivery Systems: A Concise Review.

Efficient delivery of therapeutic agents to the lesion site or specific cells is an important way to achieve "toxicity reduction and efficacy enhancement". Macrocycles have always provided many novel ideas for drug or gene loading and delivery processes. Specifically, macrocycles represented by crown ethers, cyclodextrins, cucurbit[n]urils, calix[n]arenes, and pillar[n]arenes have unique properties, which are different cavity structures, good biocompatibility, and good stability. Benefited from these diverse properties, a variety of supramolecular drug delivery systems can be designed and constructed to effectively improve the physical and chemical properties of guest molecules as needed. This review provides an outlook on the current application status and main limitations of macrocycles in supramolecular drug delivery systems.

In silico analysis of aptamer-RNA conjugate interactions with human transferrin receptor

The human transmembrane protein Transferrin Receptor-1 is regarded as a promising target for the systemic delivery of therapeutic agents, particularly of nucleic acid therapeutics, such as short double stranded RNAs. This ubiquitous receptor is involved in cellular iron uptake, keeping intracellular homeostasis. It is overexpressed in multiple cancer cell types and is internalized via clathrin-mediated endocytosis. In previous studies, a human transferrin receptor-1 RNA aptamer, identified as TR14 ST1–3, was shown to be capable of effectively internalizing into cells in culture and to deliver small, double stranded RNAs in vitro and in vivo, via systemic administration.To understand, at the molecular level, the aptamer binding to the receptor and the impact of conjugation with the therapeutic RNA, a multi-level in silico protocol was employed, including protein-aptamer docking, molecular dynamics simulations and free energy calculations. The competition for the binding pocket, between the aptamer and the natural ligand human Transferrin, was also evaluated.The results show that the aptamer binds to the same region as Transferrin, with residues from the helical domain showing a critical role. Moreover, the conjugation to the therapeutic RNA, was shown not to affect aptamer binding. Overall, this study provides an atomic-level understanding of aptamer association to human Transferrin Receptor-1 and of its conjugation with a short model-therapeutic RNA, providing also important clues for futures studies aiming to deliver other oligonucleotide-based therapeutics via Transferrin Receptor.

Engineered nanoparticles potentials in male reproduction.

The escalating prevalence of fertility problems in the aging population necessitates a comprehensive exploration of contributing factors, extending beyond environmental concerns, work-related stress, and unhealthy lifestyles. Among these, the rising incidence of testicular disorders emerges as a pivotal determinant of fertility issues. Current treatment challenges are underscored by the limitations of high-dose and frequent drug administration, coupled with substantial side effects and irreversible trauma inflicted by surgical interventions on testicular tissue. The formidable barrier posed by the blood-testis barrier compounds the complexities of treating testicular diseases, presenting a significant therapeutic obstacle. The advent of nanocarriers, with their distinctive attributes, holds promise in overcoming this impediment. These nanocarriers exhibit exceptional biocompatibility, and membrane penetration capabilities, and can strategically target the blood-testis barrier through surface ligand modification, thereby augmenting drug bioavailability and enhancing therapeutic efficacy. This review concentrates on the transformative potential of nanocarriers in the delivery of therapeutic agents to testicular tissue. By summarizing key applications, we illuminate the strides made in utilizing nanocarriers as a novel avenue to effectively treat testicular diseases. Nanocarriers are critical in delivering therapeutic agents to testicular tissue.

Extracellular Vesicles in Ovarian Cancer: From Chemoresistance Mediators to Therapeutic Vectors.

Ovarian cancer (OC) remains the deadliest gynecological malignancy, with alarming projections indicating a 42% increase in new cases and a 51% rise in mortality by 2040. This review explores the challenges in OC treatment, focusing on chemoresistance mechanisms and the potential of extracellular vesicles (EVs) as drug delivery agents. Despite advancements in treatment strategies, including cytoreductive surgery, platinum-based chemotherapy, and targeted therapies, the high recurrence rate underscores the need for innovative approaches. Key resistance mechanisms include drug efflux, apoptosis disruption, enhanced DNA repair, cancer stem cells, immune evasion, and the complex tumor microenvironment. Cancer-associated fibroblasts and extracellular vesicles play crucial roles in modulating the tumor microenvironment and facilitating chemoresistance. EVs, naturally occurring nanovesicles, emerge as promising drug carriers due to their low toxicity, high biocompatibility, and inherent targeting capabilities. They have shown potential in delivering chemotherapeutics like doxorubicin, cisplatin, and paclitaxel, as well as natural compounds such as curcumin and berry anthocyanidins, enhancing therapeutic efficacy while reducing systemic toxicity in OC models. However, challenges such as low production yields, heterogeneity, rapid clearance, and inefficient drug loading methods need to be addressed for clinical application. Ongoing research aims to optimize EV production, loading efficiency, and targeting, paving the way for novel and more effective therapeutic strategies in OC treatment. Overcoming these obstacles is crucial to unlocking the full potential of EV-based therapies and improving outcomes for OC patients.

Plant-Derived Extracellular Vesicles as a Novel Frontier in Cancer Therapeutics.

Recent advancements in nanomedicine and biotechnology have unveiled the remarkable potential of plant-derived extracellular vesicles (PDEVs) as a novel and promising approach for cancer treatment. These naturally occurring nanoscale particles exhibit exceptional biocompatibility, targeted delivery capabilities, and the capacity to load therapeutic agents, positioning them at the forefront of innovative cancer therapy strategies. PDEVs are distinguished by their unique properties that facilitate tumor targeting and penetration, thereby enhancing the efficacy of drug delivery systems. Their intrinsic biological composition allows for the evasion of the immune response, enabling the efficient transport of loaded therapeutic molecules directly to tumor sites. Moreover, PDEVs possess inherent anti-cancer properties, including the ability to induce cell cycle arrest and promote apoptotic pathways within tumor cells. These vesicles have also demonstrated antimetastatic effects, inhibiting the spread and growth of cancer cells. The multifunctional nature of PDEVs allows for the simultaneous delivery of multiple therapeutic agents, further enhancing their therapeutic potential. Engineering and modification techniques, such as encapsulation, and the loading of therapeutic agents via electroporation, sonication, and incubation, have enabled the customization of PDEVs to improve their targeting efficiency and therapeutic load capacity. This includes surface modifications to increase affinity for specific tumor markers and the encapsulation of various types of therapeutic agents, such as small molecule drugs, nucleic acids, and proteins. Their plant-derived origin offers an abundant and renewable source to produce therapeutic vesicles, reducing costs and facilitating scalability for clinical applications. This review provides an in-depth analysis of the latest research on PDEVs as emerging anti-cancer agents in cancer therapy.

Wirelessly Actuated Microfluidic Pump and Valve for Controlled Liquid Delivery in Dental Implants.

Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (<65 mT), are reported. A magnet-screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52µL in a dental implant. The liquid cargos are delivered directly to the implant-bone interface, a region traditionally difficult to access. On-demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long-term and targeted delivery of therapeutic agents in various bioengineering applications.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Extracellular Vesicles Comprising Carborane Prepared by a Host Exchanging Reaction as a Boron Carrier for Boron Neutron Capture Therapy.

With their low immunogenicity and excellent deliverability, extracellular vesicles (EVs) are promising platforms for drug delivery systems. In this study, hydrophobic molecule loading techniques were developed via an exchange reaction based on supramolecular chemistry without using organic solvents that can induce EV disruption and harmful side effects. To demonstrate the availability of an exchanging reaction to prepare drug-loading EVs, hydrophobic boron cluster carborane (CB) was introduced to EVs (CB@EVs), which is expected as a boron agent for boron neutron capture therapy (BNCT). The exchange reaction enabled the encapsulation of CB to EVs without disrupting their structure and forming aggregates. Single-particle analysis revealed that an exchanging reaction can uniformly introduce cargo molecules to EVs, which is advantageous in formulating pharmaceuticals. The performance of CB@EVs as boron agents for BNCT was demonstrated in vitro and in vivo. Compared to L-BPA, a clinically available boron agent, and CB delivered with liposomes, CB@EV systems exhibited the highest BNCT activity in vitro due to their excellent deliverability of cargo molecules via an endocytosis-independent pathway. The system can deeply penetrate 3D cultured spheroids even in the presence of extracellular matrices. The EV-based system could efficiently accumulate in tumor tissues in tumor xenograft model mice with high selectivity, mainly via the enhanced permeation and retention effect, and the deliverability of cargo molecules to tumor tissues in vivo enhanced the therapeutic benefits of BNCT compared to the L-BPA/fructose complex. All of the features of EVs are also advantageous in establishing anticancer agent delivery platforms.

Size-Controllable and Monodispersed Lipid Nanoparticle Production with High mRNA Delivery Efficiency Using 3D-Printed Ring Micromixers.

Lipid nanoparticles (LNPs) are gaining recognition as potentially effective carriers for delivery of therapeutic agents, including nucleic acids (DNA and RNA), for the prevention and treatment of various diseases. Much effort has been devoted to the implementation of microfluidic techniques for the production of monodisperse and stable LNPs and the improvement of encapsulation efficiency. Here, we developed three-dimensional (3D)-printed ring micromixers for the production of size-controllable and monodispersed LNPs with a high mRNA delivery efficiency. The effects of flow rate and ring shape asymmetry on the mixing performance were initially examined. Furthermore, the physicochemical properties (such as hydrodynamic diameter, polydispersity, and encapsulation efficiency) of the generated LNPs were quantified as a function of these physical parameters via biochemical analysis and cryo-electron microscopy imaging. With a high production rate of 68 mL/min, our 3D-printed ring micromixers can be used to manufacture LNPs with diameters less than 90 nm, low polydispersity (<0.2), and high mRNA encapsulation efficiency (>91%). Despite the simplicity of the ring-shaped mixer structure, we can produce mRNA-loaded LNPs with exceptional quality and high throughput, outperforming costly commercial micromixers.

Overcoming the Challenges in Topical Delivery of Antifungal Agents for Skin Fungal Infections

Fungal infections of the skin are a major global health concern that requires specific and efficient treatment because of their resistant nature. Antifungal drugs used topically present a viable method for targeted therapy with less systemic adverse effects. Nevertheless, a number of challenges impede the effective distribution of these substances, such as restricted skin penetration, inadequate medication retention, and the rise of resistant strains. Overcoming these challenges is very much warranted to minimize the side effects associated with long-term systemic delivery of antifungal agents. This review examines recent developments and approaches to subdue these problems and improve topical antifungal therapy efficacy. The effectiveness of several formulation strategies, including nanotechnology -based treatments, nanostructures, vesicular carriers, Gelling Systems-Polymeric Carriers, and some enhanced targeted therapies in enhancing medication penetration across the epidermal barrier is discussed. Polyenes, azoles, allylamines, echinocandins, hydroxypyridone, and other antifungals are the primary types of antifungal medications. Novel formulation techniques, such as the use of nanostructures, lipid-based carriers, and microneedle technology, show great promise for enhancing medication penetration across the skin barrier and emphasizing the significance of effective topical drug delivery. These tactics not only improve antifungal agent distribution to the intended site but also create opportunities for more focused and effective therapy. This review outlines recent developments in novel strategies used in topical carriers to boost the therapeutic performance of anti-fungal drugs with minimal side effects as compared to systemic therapy.

Normalization of Snai1-mediated vessel dysfunction increases drug response in cancer

Blood vessels in tumors are often dysfunctional. This impairs the delivery of therapeutic agents to and distribution among the cancer cells. Subsequently, treatment efficacy is reduced, and dose escalation can increase adverse effects on non-malignant tissues. The dysfunctional vessel phenotypes are attributed to aberrant pro-angiogenic signaling, and anti-angiogenic agents can ameliorate traits of vessel dysfunctionality. However, they simultaneously reduce vessel density and thereby impede drug delivery and distribution. Exploring possibilities to improve vessel functionality without compromising vessel density in the tumor microenvironment, we evaluated transcription factors (TFs) involved in epithelial-mesenchymal transition (EMT) as potential targets. Based on similarities between EMT and angiogenic activation of endothelial cells, we hypothesized that these TFs, Snai1 in particular, might serve as key regulators of vessel dysfunctionality. In vitro, experiments demonstrated that Snai1 (similarly Slug and Twist1) regulates endothelial permeability, permissiveness for tumor cell transmigration, and tip/stalk cell formation. Endothelial-specific, heterozygous knock-down of Snai1 in mice improved vascular quality in implanted tumors. This resulted in better oxygenation and reduced metastasis. Notably, the tumors in Snai1KD mice responded significantly better to chemotherapeutics as drugs were transported into the tumors at strongly increased rates and more homogeneously distributed. Thus, we demonstrate that restoring vessel homeostasis without affecting vessel density is feasible in malignant tumors. Combining such vessel re-engineering with anti-cancer drugs allows for strategic treatment approaches that reduce treatment toxicity on non-malignant tissues.

A hollow mesoporous iron oxide nanoparticle to strengthen Fenton reaction and weaken antioxidant defense systems for high efficacy tumor ferroptosis therapy

Traditional drug delivery system (DDS) such as hollow mesoporous organosilica nanoparticle (HMON) can achieve efficient delivery of ferroptosis-inducing agents for tumor therapy due to its high drug loading content (DLC), but is limited by their slow degradation and the uselessness of their silicon-based compounds. In this study, a novel hollow mesoporous superparamagnetic iron oxide nanoparticle (HMSPION) was developed with 100 nm of hollow core and 40 nm of mesoporous shell with a high DLC (up to 22.9 %) of β-Lapachone (LAP), doxorubicin (DOX), sorafenib (SFN) and/or Zn2+. Furthermore, we propose a new strategy to strengthen Fenton reaction and weaken antioxidant defense systems in tumors by co-loading Zn2+ and LAP into HMSPION to generate LAP@HMSPION@Zn. Specifically, i) LAP@HMSPION@Zn is degraded into Fe2+/3+, Zn2+, and LAP in acidic tumor microenvironment. ii) LAP catalyzes O2 to be superoxide anion radical (O2•−) and Zn2+ raises the O2•− production in mitochondria. iii) The O2•− can be catalyzed into hydrogen peroxide (H2O2) via superoxide dismutase. iv) H2O2 and the released Fe2+ accelerate the Fenton reaction, generating highly toxic hydroxyl radical (•OH). v) The Fe3+ consumes GSH and LAP downregulates GSH level by NADPH consumption, thereby relieving the antioxidant defense systems in tumor cells.

Enhanced Intratumoral Delivery of Immunomodulator Monophosphoryl Lipid A through Hyperbranched Polyglycerol–Coated Biodegradable Nanoparticles

Immunomodulatory agents (IMA) have significant potential to enhance cancer treatment but have demonstrated limited efficacy beyond the preclinical setting due to poor pharmacokinetics and toxicity associated with systemic administration. On the other hand, when locally delivered, IMAs require repeated administration to optimize immune stimulation. To overcome these challenges, we encapsulated the toll-like receptor (TLR)4 agonist monophosphoryl lipid A (MPLA) within hyperbranched polyglycerol (HPG)-coated biodegradable nanoparticles (NP) engineered for gradual drug release from the nanoparticle core, resulting in a more persistent stimulation of anti-tumor immune responses while minimizing systemic side effects. In a model of malignant melanoma, we demonstrate that HPG-NP encapsulation significantly improves the antitumor efficacy of MPLA by enhancing its ability to remodel the tumor microenvironment (TME). Compared to free MPLA, HPG-NP-MPLA significantly increased the natural killer cell and cytotoxic T cell mediated antitumor immune response and tuned the tumor draining lymph nodes towards a T helper (Th)1 response. Furthermore, when combined with local delivery of a chemotherapeutic agent, HPG-NP-MPLA induces the conversion of an immunosuppressive TME to immunogenic TME and significantly improves survival.

Nanomedicine: Innovative Strategies and Recent Advances in Targeted Cancer Therapy.

Nanomedicine's application of nanotechnology in medicine holds tremendous potential for diagnosing and treating life-threatening diseases such as cancer. Unlike conventional therapies, nanomedicine offers a promising strategy to enhance clinical outcomes while minimizing severe side effects. The principle of drug targeting enables specific delivery of therapeutic agents to their intended sites, making it a more precise and effective therapy. Combination strategies, such as the co-delivery of chemotherapeutic drugs with nucleic acids or receptor-specific molecules, are being employed to enhance therapeutic outcomes. Nanocarriers and drug delivery systems designed using these approaches offer resourceful co-delivery of therapeutic agents for anticancer therapy. Targeted drug delivery via nanotechnology-based techniques has become an urgent need and has shown significant improvements in therapeutic implications, pharmacokinetics, specificity, reduced toxicity, and biocompatibility. This review discusses the extrapolation of nanomaterials for developing innovative and novel drug delivery systems for effective anticancer therapy. Additionally, we explore the role of nanotechnology-based concepts in drug delivery research.

Pharmacokinetic Comparison of Selective Prostatic Arterial and Intravenous PSMA PET/CT Radioligand Infusions in Primary Prostatic Adenocarcinoma.

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.