Materials For Drug Delivery Research Articles

From self-Assembly to healing: Engineering ultra-Small peptides into supramolecular hydrogels for controlled drug release

The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA’s peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling. Budesonide (BUD), an anti-inflammatory drug, was selected as model because of its use in the treatment in GI disorders. Preliminary studies were performed to correlate the chemical structure of the conjugates with the key physicochemical properties of the materials for drug delivery. Two lipopeptides, MPD03 and MPD08, were found to form hydrogels (MPD03h and MPD08h, respectively) with characteristics suitable for drug delivery. These materials showed mucoadhesiveness of about 60 %. In vitro studies carried out with BUD loaded hydrogels showed about 70 % drug release within 6 h. Wound healing assessed in Caco-2 and HaCaT cells, showed reduction of cell-free area to values lower than 10 %. Taking together these results MPD03h and MPD08h have been shown to be excellent candidates for BUD delivery.

Loading co-amorphous on Metal-Organic Frameworks for gelation elimination and anti-cancer drug delivery enhancement

Troublesome gelation occurring during the dissolution of special co-amorphous (COAM) systems poses a limitation on their further applications. Metal-Organic Frameworks (MOFs) are promising porous materials for nano-scale drug delivery due to their high loading capacity and ability to control drug release. Examples of MOFs as drug carriers with the confinement effect for COAM drugs have never been reported. In this study, to eliminate the gelation of the COAM of an anti-cancer drug gefitinib (GTB) and co-former saccharin (SAC) for enhancing their anti-cancer drug delivery, a Zr-based MOF, nanoUiO-67, was selected as drug carrier. The loading process of GTB-SAC COAM on nanoUiO-67 was revealed via a real-time spinning disk confocal fluorescence microscope. The maintenance of molecular interactions between GTB and SAC in GTB-SAC COAM after loaded on nanoUiO-67 was proven experimentally and computationally, along with the host (nanoUiO-67)-guest (drug) interactions. The combined advantages of porous materials nanoMOFs and GTB-SAC COAM were fully demonstrated in terms of excellent physical stability, desirable drug release, good bio-compatibility and higher cytotoxicity towards HeLa cells. It is expected that this novel strategy could have potential application in gelation elimination and developing multi-component drug-loaded MOFs.

Novel heat exploration investigation for bioconvected Oldroyd-B nanofluid with variable thermal conductivity and Arrhenius energy induced by nailed boundary

Oldroyd-B nanofluids have potential applications in enhanced heat transfer systems, drug delivery, and advanced material processing due to their unique rheological properties. Bioconvection finds applications in biomedical research, environmental monitoring, and optimizing fluid dynamics in biotechnological and pharmaceutical processes. Due to these applications current study investigates bioconvection in the flow of Oldroyd-B nanofluid subjected to Joule heating with convected boundaries. For uniqueness of problem the effects of variable thermal connectivity and activation energy are taken into account. In addation the influence of heat source and thermal radiation are part of current model. The governing PDEs of mathematical model incorporates the Oldroyd-B rheological framework to capture the viscoelastic nature of the fluid are transformed into ODEs via similarity solution. Matlab platform via shooting algorithm is involved to solve transformed system. Through numerical simulations the stimulus of involving parameters on velocity f ′(η) temperature θ(η), concentration ϕ(η), and microbes profile X(η) are displayed in graphical and tabulated form. For strength of problem the streamlines and graphs of physical quantities are also designed. It is noted that velocity curve decreased for increasing value of magnetics parameter and opposite trend is noted in velocity distribution for increasing value of mixed convection parameter λ . Moreover, thermal layer θ is diminished for growing value of Pr , a reverse relation is noted in concentration profile for value of activation energy.

Adoption of a Tetrahedral DNA Nanostructure as a Multifunctional Biomaterial for Drug Delivery.

DNA nanostructures have been widely researched in recent years as emerging biomedical materials for drug delivery, biosensing, and cancer therapy, in addition to their hereditary function. Multiple precisely designed single-strand DNAs can be fabricated into complex, three-dimensional DNA nanostructures through a simple self-assembly process. Among all of the synthetic DNA nanostructures, tetrahedral DNA nanostructures (TDNs) stand out as the most promising biomedical nanomaterial. TDNs possess the merits of structural stability, cell membrane permeability, and natural biocompatibility due to their compact structures and DNA origin. In addition to their inherent advantages, TDNs were shown to have great potential in delivering therapeutic agents through multiple functional modifications. As a multifunctional material, TDNs have enabled innovative pharmaceutical applications, including antimicrobial therapy, anticancer treatment, immune modulation, and cartilage regeneration. Given the rapid development of TDNs in the biomedical field, it is critical to understand how to successfully produce and fine-tune the properties of TDNs for specific therapeutic needs and clinical translation. This article provides insights into the synthesis and functionalization of TDNs and summarizes the approaches for TDN-based therapeutics delivery as well as their broad applications in the field of pharmaceutics and nanomedicine, challenges, and future directions.

Optimizing Microfluidic Channel Design with High-Performance Materials for Safe Neonatal Drug Delivery.

Designing the microfluidic channel for neonatal drug delivery requires proper considerations to enhance the efficiency and safety of drug substances when used in neonates. Thus, this research aims to evaluate high-performance materials and optimize the channel design by modeling and simulation using COMSOL multiphysics in order to deliver an optimum flow rate between 0. 3 and 1 mL/hr. Some of the materials used in the study included PDMS, glass, COC, PMMA, PC, TPE, and hydrogels, and the evaluation criterion involved biocompatibility, mechanical properties, chemical resistance, and ease of fabrication. The simulation was carried out in the COMSOL multiphysics platform and demonstrated the fog fluid behavior in different channel geometries, including laminar flow and turbulence. The study then used systematic changes in design parameters with the aim of establishing the best implementation models that can improve the efficiency and reliability of the drug delivery system. The comparison was based mostly on each material and its appropriateness in microfluidic usage, primarily in neonatal drug delivery. The biocompatibility of the developed materials was verified using the literature analysis and adherence to the ISO 10993 standard, thus providing safety for the use of neonatal devices. Tensile strength was included to check the strength of each material to withstand its operation conditions. Chemical resistance was also tested in order to determine the compatibility of the materials with various drugs, and the possibility of fabrication was also taken into consideration to identify appropriate materials that could be used in the rapid manufacturing of the product. The results we obtained show that PDMS, due to its flexibility and simplicity in simulation coupled with more efficient channel designs which have been extracted from COMSOL, present a feasible solution to neonatal drug delivery. The present comparative study serves as a guide on the choice of materials and design of microfluidic devices to help achieve safer and enhanced drug delivery systems suitable for the delicate reception of fragile neonates.

PH-induced fluorescent active sodium alginate-based ionically conjugated and REDOX responsive multi-functional microgels for the anticancer drug delivery

A sodium alginate (Alg) based REDOX (reduction and oxidation)-responsive and fluorescent active microgel was prepared via water in oil (w/o) mini-emulsion polymerization technique. Here, we initially synthesized sodium alginate-based disulfide cross linked microgels and after that those microgels were tagged with rhodamine amine derivative (RhB-NH2) by ionic interaction to get the pH-responsive fluorescent property. Functionalized microgels were characterized using 1H NMR, FTIR, DLS, HRTEM, FESEM, UV–vis, and fluorescence spectroscopy analyses. Presence of the REDOX-responsive disulfide-containing crosslinkers in the microgels enhances the release of doxorubicin (DOX), an anti-cancer drug in the reducing environment of the cancer-cells (simulated). Existence of the rhodamine-amine derivative in the microgels triggers the pH-dependent fluorescence property by showing fluorescence emission at 560–580 nm at pH 5.5 (cancer cell pH). The cytotoxicity of the biopolymer based microgel was assessed over both cancerous HeLa (IC50 100 µg/mL) and non-cancerous MDCK (IC50 200 µg/mL) cells by MTT assay which showed the synthesized microgel is non-toxic whereas DOX-loaded microgels showed significant toxicity. FACS and cell uptake (in vitro) analyses were conducted to understand the cell apoptosis cycle and behavior of the cancer cells in presence of the DOX-loaded microgels. This pH-responsive fluorescent active alginate-based biomaterial could be a promising material for the anti-cancer drug delivery and other medical fields.

Nanocellulose/Nanoporous Silicon Composite Films as a Drug Delivery System.

Nanocellulose (NC) is a promising material for drug delivery due to its high surface area-to-volume ratio, biocompatibility, biodegradability, and versatility in various formats (nanoparticles, hydrogels, microspheres, membranes, and films). In this study, nanocellulose films were derived from "Bolaina blanca" (Guazuma crinita) and combined with nanoporous silicon microparticles (nPSi) in concentrations ranging from 0.1% to 1.0% (w/v), using polyvinyl alcohol (PVA) as a binding agent to create NC/nPSi composite films for drug delivery systems. The physicochemical properties of the samples were characterized using UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The mechanical properties and drug release capabilities were also evaluated using methylene blue (MB) as an antibacterial drug model. Antibacterial assays were conducted against S. aureus and E. coli bacteria. The results show that NC/nPSi composites with 1% nPSi increased the T50% by 10 °C and enhanced mechanical properties, such as a 70% increase in the elastic modulus and a 372% increase in elongation, compared to NC films. Additionally, MB released from NC/nPSi composites effectively inhibited the growth of both bacteria. It was also observed that the diffusion coefficients were inversely proportional to the % nPSi. These findings suggest that this novel NC/nPSi-based material can serve as an effective controlled drug release system.

The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations. Various biomedical applications of HNTs are derived from hollow tubular structures, high mechanical strength, good biocompatibility, bioactivity, and unique surface characteristics. This natural nanomaterial is safe, abundantly available, and may be processed with environmentally safe green chemistry methods. This review describes the structure and physicochemical properties of HNTs relative to bioactivity. We discuss surface area, porosity and surface defects, hydrophilicity, heterogeneity and charge of external and internal surfaces, as well as biosafety. The paper provides comprehensive guidance for the development of this tubule nanoclay and its advanced biomedical applications for clinical diagnosis and therapy.

Enhancing camptothecin loading and release control through physical surface modification of organosilica nanoparticles with polyethylene glycol

The surface modification of nanoparticles holds the potential to enhance the loading capacity of drug molecules and regulate their release, making it possible to exploit the differences between tumor and normal cells. To this end, the surfaces of tetrasulfide-based phenylene-containing biodegradable periodic mesoporous organosilica (BPMO) nanoparticles (designated P4S) are modified herein with a hydrophilic and biocompatible polyethylene glycol (PEG) polymer. The PEG coating is optimized by adjusting the PEG concentration during synthesis, thus resulting in a significant increase in the nanoparticle stability. Furthermore, PEG modification enhances the nanoparticles' camptothecin (CPT) loading capacity. Drug release assessments under physical and acidic pH conditions demonstrate the pH-responsive properties of the P4S nanoparticles upon PEG functionalization, which results in increased drug release at low pH, along with enhanced cellular uptake potential. Notably, the cytotoxicity of CPT against HepG2 cancer cells is significantly improved when loaded into the P4S-PEG nanoparticles. These findings reveal the efficacy of PEG surface modification of the drug-delivery material in augmenting the activity of CPT, with promising prospects for clinical applications.

A Systematic Review: Chitosan/ Poly (vinyl alcohol) based Hydrogel composites for Drug Delivery Material

A Systematic Review: Chitosan/ Poly (vinyl alcohol) based Hydrogel composites for Drug Delivery Material

Intranasal delivery of liposome encapsulated flavonoids ameliorates l-DOPA induced dyskinesia in hemiparkinsonian mice

In the present study, we explored the development of a novel noninvasive liposomal drug delivery material for use in intranasal drug delivery applications in human diseases. We used drug entrapment into liposomal nanoparticle assembly to efficiently deliver the drugs to the nasal mucosa to be delivered to the brain. The naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF) has previously been shown to have beneficial effects in ameliorating Parkinson's disease (PD). We used both naturally occurring 7,8-DHF and the chemically modified form of DHF, the DHF-ME, to be used as a drug candidate for the treatment of PD and l-DOPA induced dyskinesia (LID), which is the debilitating side effect of l-DOPA therapy in PD. The ligand-protein interaction behavior for 7,8-DHF and 6,7-DHF-ME was found to be more effective with molecular docking and molecular stimulation studies of flavonoid compounds with TrkB receptor. Our study showed that 7,8-DHF delivered via intranasal route using a liposomal formulation ameliorated LID in hemiparkinsonian mice model when these mice were chronically administered with l-DOPA, which is the only current medication for relieving the clinical symptoms of PD. The present study also demonstrated that apart from reducing the LID, 7,8-DHF delivery directly to the brain via the intranasal route also corrected some long-term signaling adaptations involving ΔFosB and α Synuclein in the brain of dopamine (DA) depleted animals.

From Crystalline to Amorphous Structure of Carbamazepine Regulated by Dipeptide-Based Supramolecular Gel

Many solid drugs exist in polycrystalline state, which markedly hinder their pharmacological effectiveness. Given the designability and biocompatibility, the development of peptide-based supramolecular gel that can regulate crystal growth of drug has a strong potential. In this research, the polycrystalline drug carbamazepine (CBZ) was successfully transformed from orthorhombic dihydrate into amorphous form through the introduction of 9-fluorenylmethoxycarbonyl diphenylalanine (FmocFF) gel and co-assembled supramolecular gel was obtained. The intermolecular mechanism of structural transformation was elucidated in detail by various spectral techniques. The dihydrate of CBZ was restrained through the inhibition of hydration of the NH2 groups and the π-π stacking interaction among the aromatic rings of FmocFF and CBZ. Especially, principal component analysis (PCA), and two-dimensional correlation spectroscopy (2DCOS) techniques were conducted to analyze the time-dependent IR spectra, which indicated that the π-π stacking interaction mainly affected the FmocFF gel fiber elongation after co-assembly with CBZ. In addition, the FmocFF gel matrix significantly influenced the release behavior of CBZ in vitro, which providing theoretical guidance for the development of short-peptide assembly strategies in drug delivery materials.

Impact of ZnO nanoparticles on Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposites as antibacterial agents and drug loading materials

A series of Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposites were successfully synthesized using the hydrothermal method with different ZnO masses. The novelty of this study was the obtained Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposite as a good candidate as an antibacterial agent and drug delivery material. The IR spectra showed that the samples were successfully formed. The vibrations of Fe–O and Mn–O were detected at 678.94–563.21cm−1, and that of Zn–O was located at 933.55–867.97cm−1. Meanwhile, the XRD pattern showed that the samples have two crystal phases, i.e. magnetite and ZnO. The nanostructure of the samples was studied by SAXS, showing that the Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposite formed clustering particles that were structured by secondary and primary particles. The secondary particles in the samples contained about 3–4 primary particles. The magnetic properties were characterized using VSM, showing that the samples have superparamagnetic behavior. The increase in ZnO mass affected the saturation magnetization value. The highest saturation magnetization value was approximately 8.66 emu/g for the sample with the smallest ZnO mass. The samples contained Fe2+, Fe3+, and ZnO2+ ions, which created oxidative stress that damaged the DNA cells of bacteria, as seen from the results of the antibacterial activity test. In addition, it was found that the Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposite has another potential as a drug loader material. As the ZnO mass increased, the drug loading efficiency also increased up to 75%. Thus, the prepared Mn0.5Fe2.5O4@C/ZnO-DOX nanocomposites have potential as antibacterial agents and drug loading materials.

Exploring the Potential of MIM-Manufactured Porous NiTi as a Vascular Drug Delivery Material.

Porous nickel-titanium (NiTi) manufactured using metal injection molding (MIM) has emerged as an innovative generation of drug-loaded stent materials. However, an increase in NiTi porosity may compromise its mechanical properties and cytocompatibility. This study aims to explore the potential of porous NiTi as a vascular drug delivery material and evaluate the impact of porosity on its drug loading and release, mechanical properties, and cytocompatibility. MIM, combined with the powder space-holder method, was used to fabricate porous NiTi alloys with three porosity levels. The mechanical properties of porous NiTi were assessed, as well as the surface cell growth capability. Furthermore, by loading rapamycin nanoparticles onto the surface and within the pores of porous NiTi, we evaluated the in vitro drug release behavior, inhibitory effect on cell proliferation, and inhibition of neointimal hyperplasia in vivo. The results demonstrated that an increase in porosity led to a decrease in the mechanical properties of porous NiTi, including hardness, tensile strength, and elastic modulus, and a decrease in the surface cell growth capability, affecting both cell proliferation and morphology. Concurrently, the loading capacity and release duration of rapamycin were extended with increasing porosity, resulting in enhanced inhibitory effects on cell proliferation in vitro and inhibition of neointimal hyperplasia in vivo. In conclusion, porous NiTi holds promise as a desirable vascular drug delivery material, but a balanced consideration of the influence of porosity on both mechanical properties and cytocompatibility is necessary to achieve an optimal balance among drug-loading and release performance, mechanical properties, and cytocompatibility.

PEGose Block Poly(lactic acid) Nanoparticles for Cargo Delivery.

Hydrophilic polymers have found ubiquitous use in drug delivery and novel polymer materials to advance drug delivery systems are highly sought after. Herein, an amylose mimic (PEGose) was combined with poly(lactic acid) (PLA) in an amphiphilic block copolymer to form PEG-free nanoparticles as an alternative to PEG-based nanomedicines. The block copolymer self-assembled into 150-200 nm particles with a narrow dispersity in aqueous environment. The formed nanoparticles were capable of encapsulation, the sustained release of both hydrophilic and hydrophobic dyes. Moreover, the nanoparticles were found to be remarkably stable and had a very low cytotoxicity and a high propensity to penetrate cells. These results highlight the potential of PEGose-b-PLA to be used in drug delivery with a new hydrophilic building block.

Binding Site Programmable Self-Assembly of 3D Hierarchical DNA Origami Nanostructures.

DNA nanotechnology has broad applications in biomedical drug delivery and programmable materials. Characterization of the self-assembly of DNA origami and quantum dots (QDs) is necessary for the development of new DNA-based nanostructures. We use computation and experiment to show that the self-assembly of 3D hierarchical nanostructures can be controlled by programming the binding site number and their positions on DNA origami. Using biotinylated pentagonal pyramid wireframe DNA origamis and streptavidin capped QDs, we demonstrate that DNA origami with 1 binding site at the outer vertex can assemble multimeric origamis with up to 6 DNA origamis on 1 QD, and DNA origami with 1 binding site at the inner center can only assemble monomeric and dimeric origamis. Meanwhile, the yield percentages of different multimeric origamis are controlled by the QD:DNA-origami stoichiometric mixing ratio. DNA origamis with 2 binding sites at the αγ positions (of the pentagon) make larger nanostructures than those with binding sites at the αβ positions. In general, increasing the number of binding sites leads to increases in the nanostructure size. At high DNA origami concentration, the QD number in each cluster becomes the limiting factor for the growth of nanostructures. We find that reducing the QD size can also affect the self-assembly because of the reduced access to the binding sites from more densely packed origamis.

Defective MOFs as nano carrier for drug loading with controlled release

Metal-organic frameworks (MOFs) are considered highly promising nanomedicine carriers due to their well-defined structures, high specific surface area and porosity, adjustable pore size, and ease of chemical functionalization. However, traditional MOFs face limitations in lattice size and strong non-covalent interactions between the host and guest, posing significant challenges for high and responsive drug loading. In this study, defect-engineered MOFs (UiO-66-NH2) with uniform mesopores were successfully prepared by reducing ligands and adding modulators. Compared to perfect UiO-66-NH2, the loading capacity of the defective UiO-66-NH2 increased more than twofold. Utilizing phase change material as a trigger for drug release, precise temperature-responsive drug release was accomplished. This offers a novel strategy for MOFs materials in drug delivery and controlled release. This study will aid future efforts in using MOFs for selective drug delivery to cells, particularly in cancer treatment and related fields.

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

A superabsorbent and pH-responsive copolymer-hydrogel based on acemannan from Aloe vera (Aloe barbadensis M.): A smart material for drug delivery

Combining natural polysaccharides with synthetic materials improves their functional properties which are essential for designing sustained-release drug delivery systems. In this context, the Aloe vera leaf mucilage/hydrogel (ALH) was reacted with acrylic acid (AA) to synthesize a copolymerized hydrogel, i.e., ALH-grafted-Polyacrylic acid (ALH-g-PAA) through free radical copolymerization. Concentrations of the crosslinker N,N′-methylene-bis-acrylamide (MBA), and the initiator potassium persulfate (KPS) were optimized to study their effects on ALH-g-PAA swelling. The FTIR and solid-state NMR (CP/MAS 13C NMR) spectra witnessed the formation of ALH-g-PAA. Scanning electron microscopy (SEM) analysis revealed superporous nature of ALH-g-PAA. The gel fraction (%) of ALH-g-PAA was directly related to the concentrations of AA and MBA whereas the sol fraction was inversely related to the concentrations of AA and MBA. The porosity (%) of ALH-g-PAA directly depends on the concentration of AA and MBA. The ALH-g-PAA swelled admirably at pH 7.4 and insignificantly at pH 1.2. The ALH-g-PAA offered on/off switching properties at pH 7.4/1.2. The metoprolol tartrate was loaded on different formulations of ALH-g-PAA. The ALH-g-PAA showed pH, time, and swelling-dependent release of metoprolol tartrate (MT) for 24 h following the first-order kinetic and Korsmeyer-Peppas model. Haemocompatibility studies ascertained the non-thrombogenic and non-hemolytic behavior of ALH-g-PAA.

Catheter-Directed Ionic Liquid Embolic Agent for Rapid Portal Vein Embolization, Segmentectomy, and Bile Duct Ablation.

Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, is developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization, liver ablation, and drug delivery. LEAD is optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non-survival and survival porcine experiments, successful PVE is achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug-resistant patient-derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth.