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Showing papers on "Drug carrier published in 2009"


Journal ArticleDOI
TL;DR: In this paper, a superparamagnetic graphene oxide-Fe3O4nanoparticles hybrid was prepared via a simple and effective chemical precipitation method, which was then loaded with doxorubicin hydrochloride (DXR) and the loading capacity was as high as 1.08 mg mg−1.6 wt% by atomic absorption spectrometry.
Abstract: A superparamagnetic graphene oxide –Fe3O4nanoparticles hybrid (GO–Fe3O4) was prepared via a simple and effective chemical precipitation method. The amount of loading of Fe3O4 on GO was estimated as 18.6 wt% by atomic absorption spectrometry. The hybrid was then loaded with doxorubicin hydrochloride (DXR) and the loading capacity was as high as 1.08 mg mg−1. Both of the GO–Fe3O4 hybrids before and after loading with DXR can be dispersed well in aqueous solution. They can congregate under acidic conditions and move regularly under the force of an external magnet. Furthermore, the aggregated hybrid can be redispersed to form a stable suspension under basic conditions. These properties make it a potential candidate for controlled targeted drug delivery and release.

979 citations


Journal ArticleDOI
09 Sep 2009-ACS Nano
TL;DR: It is demonstrated that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity.
Abstract: Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 kD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 kD PEI polymer were particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in >70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the nontoxic cationic MSNP enhances the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.

842 citations


Journal ArticleDOI
TL;DR: This review will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery, including a review of current activities in the field of liposomes, and challenging issues of targeting and triggering will be discussed in detail.
Abstract: In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.

768 citations


Journal ArticleDOI
TL;DR: The success and degree of muco-adhesive bonding is influenced by various polymer-based properties such as the degree of cross-linking, chain length and the presence of various functional groupings as mentioned in this paper.

720 citations


Journal ArticleDOI
TL;DR: In this Account, examples from in vivo studies are discussed that demonstrate how polymer architectural features impact the renal filtration of a polymer as well as tumor penetration and tumor accumulation, thus improving therapeutic effectiveness.
Abstract: Chemotherapy can destroy tumors and arrest cancer progress. Unfortunately, severe side effects (treatment is usually a series of injections of highly toxic drugs) often restrict the frequency and size of dosages, much to the detriment of tumor inhibition. Most chemotherapeutic drugs have pharmacokinetic profiles with tremendous potential for improvement. Water-soluble polymers offer the potential to increase drug circulation time, improve drug solubility, prolong drug residence time in a tumor, and reduce toxicity. Cytotoxic drugs that are covalently attached to water-soluble polymers via reversible linkages more effectively target tumor tissue than the drugs alone. Macromolecules passively target solid tumor tissue through a combination of reduced renal clearance and exploitation of the enhanced permeation and retention (EPR) effect, which prevails for fast-growing tumors. Effective drug delivery involves a balance between (i) elimination of the polymeric drug conjugate from the bloodstream by the kidneys, liver, and other organs and (ii) movement of the drug out of the blood vasculature and into the tumor (that is, extravasation). Polymers are eliminated in the kidney by filtration through pores with a size comparable to the hydrodynamic diameter of the polymer; in contrast, the openings in the blood vessel structures that traverse tumors are an order of magnitude greater than the diameter of the polymer. Thus, features that may broadly be grouped as the "molecular architecture" of the polymer, such as its hydrodynamic volume (or molecular weight), molecular conformation, chain flexibility, branching, and location of the attached drug, can greatly impact elimination of the polymer from the body through the kidney but have a much smaller effect on the extravasation of the polymer into the tumor. Molecular architecture can in theory be adjusted to assert essentially independent control over elimination and extravasation. Understanding how molecular architecture affects passage of a polymer through a pore is therefore essential for designing polymer drug carriers that are effective in passively delivering a drug payload while conforming to the requirement that the polymers must eventually be eliminated from the body. In this Account, we discuss examples from in vivo studies that demonstrate how polymer architectural features impact the renal filtration of a polymer as well as tumor penetration and tumor accumulation. In brief, features that inhibit passage of a polymer through a pore, such as higher molecular weight, decreased flexibility, and an increased number of polymer chain ends, help prevent elimination of the polymer by the kidneys and can improve blood circulation times and tumor accumulation, thus improving therapeutic effectiveness.

640 citations


Journal ArticleDOI
TL;DR: In this article, the authors present a review of the recent developments in this field, and focus on two categories of PNIPAAm-based copolymer micelles as smart drug delivery systems.

635 citations


Journal ArticleDOI
TL;DR: Evidence is provided that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin.

576 citations


Journal ArticleDOI
TL;DR: Given such favorable properties including low toxicity, biocompatibility, and fast uptake by several nondestructive endocytic pathways, the HGC nanoparticles may serve as a versatile carrier for the intracellular delivery of therapeutic agents.

540 citations


Journal ArticleDOI
TL;DR: Artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100 nm size, near monodisperse nanoparticles upon conjugation of diverse hydrophobic molecules, including chemotherapeutics are developed.
Abstract: New strategies to self-assemble biocompatible materials into nanoscale, drug-loaded packages with improved therapeutic efficacy are needed for nanomedicine. To address this need, we developed artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100-nm-sized, near-monodisperse nanoparticles on conjugation of diverse hydrophobic molecules, including chemotherapeutics. These CPs consist of a biodegradable polypeptide that is attached to a short Cys-rich segment. Covalent modification of the Cys residues with a structurally diverse set of hydrophobic small molecules, including chemotherapeutics, leads to spontaneous formation of nanoparticles over a range of CP compositions and molecular weights. When used to deliver chemotherapeutics to a murine cancer model, CP nanoparticles have a fourfold higher maximum tolerated dose than free drug, and induce nearly complete tumour regression after a single dose. This simple strategy can promote co-assembly of drugs, imaging agents and targeting moieties into multifunctional nanomedicines.

531 citations


Journal ArticleDOI
TL;DR: The state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drug delivery devices to enhance the material's functionality in tissue engineering applications is discussed.

493 citations


Journal ArticleDOI
TL;DR: These new nano-cargos have the ability to encapsulate efficiently lipophilic drugs, offering a pharmaceutical solution for their intravenous administration and should reduce considerably the cost and convenience for treatment.

Journal ArticleDOI
03 Aug 2009-Small
TL;DR: In this Review, the recent strategic development of drug delivery is discussed with emphasis on polymer-based, especially protein- based, nanomedicine platforms for drug delivery, including protein cages, microspheres, nanoparticles, hydrogels, films, minirods, and minipellets.
Abstract: Protein-based nanomedicine platforms for drug delivery comprise naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug-delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug-delivery systems, including the ferritin/apoferritin protein cage, plant-derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms, including various protein cages, microspheres, nanoparticles, hydrogels, films, minirods, and minipellets. The protein cage is the most newly developed biomaterial for drug delivery and therapeutic applications. The uniform size, multifunctionality, and biodegradability push it to the frontier of drug delivery. In this Review, the recent strategic development of drug delivery is discussed with emphasis on polymer-based, especially protein-based, nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein-based drug-delivery system.

Journal ArticleDOI
TL;DR: The size of anticancer agent‐incorporating micelles can be controlled within the diameter range of 20–100 nm to ensure that they do not penetrate normal vessel walls to reduce the incidence of drug‐induced side‐effects.
Abstract: The size of anticancer agent-incorporating micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non-specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water-insoluble drug can be incorporated into polymer micelles. Presently, several anticancer agent-incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid-incorporating micelle carrier systems are also being developed.

Journal ArticleDOI
TL;DR: This review focuses on recent developments concerning stimuli- responsive polymersomes made of amphiphilic block copolymers and their potential applications within the biomedical field.
Abstract: Polymeric formulations (micelles, vesicles etc.) have emerged as versatile drug carriers due to their increased stability, site specificity, blood circulation resistance and thus overall potential therapeutic effects compared to liposomes. Furthermore, stimuli-responsive systems have been developed whose properties change after applying certain external triggers. Polymersomes are mainly composed of amphiphilic block copolymers that are held together in water due to strong physical interactions between the insoluble hydrophobic blocks, thus forming a bilayer morphology or, in the case of triblock copolymers, a bilayer-like morphology. Formation and destabilization of these assemblies is a consequence of external stimuli (temperature, pH, oxidation/reduction conditions etc.). This review focuses on recent developments concerning stimuli- responsive polymersomes made of amphiphilic block copolymers and their potential applications within the biomedical field.

Journal ArticleDOI
TL;DR: DNPs have been shown to be amenable to targeting of the drug to the site of action, leading to a decreases in the dose required and a decrease in side effects, which makes them a novel polymeric drug delivery device, which fulfils the requirements for ophthalmic application.

Journal ArticleDOI
TL;DR: Low pH-responsive PHNPs of Fe(3)O(4) can be exploited as a cisplatin delivery vehicle for target-specific therapeutic applications, and is reported to be able to target to breast cancer SK-BR-3 cells with IC(50) reaching 2.9 muM, much lower than 6.8 muM needed for free cisPlatin.
Abstract: We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe3O4. We prepared the PHNPs by controlled oxidation of Fe NPs at 250 °C followed by acid etch...

Journal ArticleDOI
TL;DR: This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects.
Abstract: The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed.

Journal ArticleDOI
TL;DR: Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.
Abstract: Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.

Journal ArticleDOI
TL;DR: An anticancer drug was conjugated to the surface of gold nanoparticles through a photocleavable o-nitrobenzyl linkage, providing a nontoxic conjugate that effectively releases the payload upon long wavelength UV irradiation.
Abstract: An anticancer drug (5-fluorouracil) was conjugated to the surface of gold nanoparticles through a photocleavable o-nitrobenzyl linkage. In this system, the particle serves as both cage and carrier for the therapeutic, providing a nontoxic conjugate that effectively releases the payload upon long wavelength UV irradiation.

Journal ArticleDOI
TL;DR: The use of polymers for local drug delivery has greatly expanded the spectrum of drugs available for the treatment of brain diseases, such as malignant tumours and Alzheimer’s disease and the present review provides an insight into some of the recent advances made.
Abstract: Being the most delicate organ of the body, the brain is protected against potentially toxic substances by the blood-brain barrier (BBB), which restricts the entry of most pharmaceuticals into the brain. The developmental process for new drugs for the treatment of CNS disorders has not kept pace with progress in molecular neurosciences because most of the new drugs discovered are unable to cross the BBB. The clinical failure of CNS drug delivery may be attributed largely to a lack of appropriate drug delivery systems. Localized and controlled delivery of drugs at their desired site of action is preferred because it reduces toxicity and increases treatment efficiency. The present review provides an insight into some of the recent advances made in the field of brain drug delivery.The various strategies that have been explored to increase drug delivery into the brain include (i) chemical delivery systems, such as lipid-mediated transport, the prodrug approach and the lock-in system; (ii) biological delivery systems, in which pharmaceuticals are re-engineered to cross the BBB via specific endogenous transporters localized within the brain capillary endothelium; (iii) disruption of the BBB, for example by modification of tight junctions, which causes a controlled and transient increase in the permeability of brain capillaries; (iv) the use of molecular Trojan horses, such as peptidomimetic monoclonal antibodies to transport large molecules (e.g. antibodies, recombinant proteins, nonviral gene medicines or RNA interference drugs) across the BBB; and (v) particulate drug carrier systems. Receptor-mediated transport systems exist for certain endogenous peptides, such as insulin and transferrin, enabling these molecules to cross the BBB in vivo.The use of polymers for local drug delivery has greatly expanded the spectrum of drugs available for the treatment of brain diseases, such as malignant tumours and Alzheimer's disease. In addition, various drug delivery systems (e.g. liposomes, microspheres, nanoparticles, nanogels and bionanocapsules) have been used to enhance drug delivery to the brain. Recently, microchips and biodegradable polymers have become important in brain tumour therapy.The intense search for alternative routes of drug delivery (e.g. intranasal drug delivery, convection-enhanced diffusion and intrathecal/intraventricular drug delivery systems) has been driven by the need to overcome the physiological barriers of the brain and to achieve high drug concentrations within the brain. For more than 30 years, considerable efforts have been made to enhance the delivery of therapeutic molecules across the vascular barriers of the CNS. The current challenge is to develop drug delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner.

Journal ArticleDOI
Shaojun Guo1, Dan Li1, Lixue Zhang1, Jing Li1, Erkang Wang1 
TL;DR: The results indicate that the MSSMN has a high drug loading capacity and favorable release property for Dox; thus, it is very promising for the application in drug delivery.

Journal ArticleDOI
TL;DR: Hydthermal synthesized Fe3O4 microspheres have been encapsulated with nonporous silica and a further layer of ordered mesoporous silica through a simple sol-gel process to investigate the storage and release properties using ibuprofen (IBU) as model drug by the surface modification.

Journal ArticleDOI
TL;DR: The covalent conjugation of drug and aptamer creates alternative opportunities for targeted therapy, as multiple yet specific aptamers can be “generated” relatively easily by cell‐SELEX for any target cells; this demonstrates the full potential of cell‐ SELEX as a molecular discovery tool for biomedical studies and drug development.
Abstract: The conjugation of antitumor drugs to targeting reagents such as antibodies is a promising method that can increase the efficacy of chemotherapy and reduce the overall toxicity of the drugs. In this study, we covalently link the antitumor agent doxorubicin (Dox) to the DNA aptamer sgc8c, which was selected by the cell-SELEX method. In doing so, we expected that this sgc8c-Dox conjugate would specifically kill the target CCRF-CEM (T-cell acute lymphoblastic leukemia, T-cell ALL) cells, but with minimal toxicity towards nontarget cells. The results demonstrated that the sgc8c-Dox conjugate possesses many of the properties of the sgc8c aptamer, including high binding affinity (K(d)=2.0+/-0.2 nM) and the capability to be efficiently internalized by target cells. Moreover, due to the specific conjugation method, the acid-labile linkage connecting the sgc8c-Dox conjugate can be cleaved inside the acidic endosomal environment. Cell viability tests demonstrate that the sgc8c-Dox conjugates not only possess potency similar to unconjugated Dox, but also have the required molecular specificity that is lacking in most current targeted drug delivery strategies. Furthermore, we found that nonspecific uptake of membrane-permeable Dox to nontarget cell lines could also be inhibited by linking the drug with the aptamer; thus, the conjugates are selective for cells that express higher amounts of target proteins. Compared to the less effective Dox-immunoconjugates, these sgc8c-Dox conjugates make targeted chemotherapy more feasible with drugs having various potencies. When combined with the large number of recently created DNA aptamers that specifically target a wide variety of cancer cells, this drug-aptoconjugation method will have broad implications for targeted drug delivery.

Journal ArticleDOI
TL;DR: The lead formulation developed is liver targeted and can induce fully reversible, long-duration gene silencing without loss of activity following repeat administration, and shows that in vivo delivery efficacy is affected by many parameters, including the formulation composition, nature of particle PEGylation, degree of drug loading, and biophysical parameters such as particle size.

Journal ArticleDOI
TL;DR: Inspired by this natural example, RBC-mimicking particles are synthesized that mimic the key structural and functional features of RBCs and possess the ability to carry oxygen and flow through capillaries smaller than their own diameter.
Abstract: Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.

Journal ArticleDOI
TL;DR: Results suggest that H40-P(LA-DOX)-b-PEG-OH/FA micelles could be a promising nanocarrier with excellent in vivo stability for targeting the drugs to cancer cells and releasing the drug molecules inside the cells by sensing the acidic environment of the endosomal compartments.

Journal ArticleDOI
TL;DR: In vivo, the targeting of anti-cancer drug to tumor endothelium by RGD-labeled NP is a promising approach and is demonstrated to be more effective in vitro and in vivo than taxol.

Journal ArticleDOI
TL;DR: This review examines the engineered polymers that have been used as traditional drug delivery systems and as more recent applications in nanotechnology.

Journal ArticleDOI
TL;DR: In this article, an on-off release of sodium fluorescein over multiple magnetic cycles has been successfully demonstrated using prototype membrane-based devices and the total drug dose delivered was directly proportional to the duration of the “on” pulse.
Abstract: Nanocomposite membranes based on thermosensitive, poly(N-isopropylacrylamide)-based nanogels and magnetite nanoparticles have been designed to achieve “on-demand” drug delivery upon the application of an oscillating magnetic field. On−off release of sodium fluorescein over multiple magnetic cycles has been successfully demonstrated using prototype membrane-based devices. The total drug dose delivered was directly proportional to the duration of the “on” pulse. The membranes were noncytotoxic, were biocompatible, and retained their switchable flux properties after 45 days of subcutaneous implantation.

Journal ArticleDOI
TL;DR: Results suggest that the use of targeted, dual agent nanoparticles delivering a combination of P-gp modulator and anticancer drug is a very promising approach to overcome tumor drug resistance.