Nanoparticle-based Drug Delivery Systems Research Articles

Oriented attachment of VNAR proteins, via site-selective modification, on PLGA-PEG nanoparticles enhances nanoconjugate performance.

Herein we report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis. We exploit a Variable New Antigen Receptor (VNAR) domain, conjugated using site-specific chemistry, to direct poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles to delta like canonical Notch ligand 4 (DLL4). The importance of site-specific chemistry is demonstrated.

Combinatorial Nanoparticle Delivery of siRNA and Antineoplastics for Lung Cancer Treatment.

Recent developments in nanotechnology, especially in drug delivery systems, are advanced by featuring novel multifunctional nanoparticles that promise safe, specific, and efficient therapeutic delivery for cancer treatment. Multifunctional nanoparticle-based drug delivery systems enable simultaneous delivery of multiple therapeutic agents for effective combination therapy for cancer. In this chapter, we provide detailed protocols for development and application of a multifunctional nanoparticle system for combinatorial delivery of a chemotherapeutic (cisplatin) and small interfering RNA (siRNA) for human antigen R (HuR) mRNA in cancer cells using a polyamidoamine (PAMAM) dendrimer platform. Protocols for nanoparticle functionalization with folic acid (FA) for targeted delivery of therapeutics toward folate receptor (FR)-overexpressing cancer cells are also described. Further, methods employed for physiochemical and functional characterization of the multifunctional nanoparticle system are discussed in detail. Using the methods described in this chapter, researchers would be able to develop PAMAM dendrimer-based multifunctional nanoparticles for targeted delivery of chemotherapeutics and siRNA combinations. We also provide an example showing the dendrimer-polyethyleneimine-cis-diamminedichloroplatinum-siRNA-folic acid (Den-PEI-CDDP-siRNA-FA) nanoparticle system developed was therapeutically effective toward non-small cell lung cancer (NSCLC) cell lines (H1299 and A549) while exhibiting reduced toxicity to normal lung fibroblast (MRC9) cells.

Nanoparticle-Based Drug Delivery Systems for Enhanced Tumor-Targeting Treatment.

The encapsulation of targeting agents into nanoscale drug delivery systems (DDS) for cancer therapy has received considerable attention in recent years. The thriving area of cancer nanotechnology provides a unique and comprehensive anticancer approach through early diagnosis, prediction, prevention, and personalized medical therapy, preferentially vital in target-specific drug curative strategies. In this review, the concept of cancer nanotechnology and its areas of specialty are introduced, followed by a detailed presentation of specific targeting methods and various nanoparticle (NP) drug delivery systems. The technical bottleneck attached to the clinical translation and nanotoxicity issues is emphasized for future breakthroughs, that will boost drug efficacy to a higher level with the assistance of nanotechnology.

In vivo evaluation of anticancer efficacy of drug loaded cockle shell-derived aragonite nanoparticles.

Doxorubicin (DOX) is an effective and commonly used anthracycline anticancer drug for the treatment of osteosarcoma (OS). However, its antitumor effect is hampered by the nonspecific distribution and significant adverse effects. Nanoparticles based drug delivery systems are promising approaches to maximize the anticancer efficacy while decrease the side effects. In this study, biogenic aragonite nanoparticles (ANPs) were developed from cockle shells and loaded with DOX. An orthotopic rat OS model was induced by UMR-106 cells tibia cavity injection. The anticancer efficacy study included five groups: normal control group, OS model group, free DOX group (2 mg/kg), DOX-ANPs 1 group (2 mg of equivalent DOX/kg) and DOX-ANPs 2 group (1.5 mg of equivalent DOX/kg). This study demonstrates that the DOX-ANPs treatment groups can significantly reduce the tumor volume and increase the surviving ratio as compared to the OS model group. In addition, these two DOX-ANPs groups showed less toxicity to the normal organs compared to the free DOX group. Furthermore, DOX-ANPs 2 group showed the similar anticancer efficacy as DOX-ANPs 1 group, which suggested that DOX loaded onto the ANPs may allow the reduction of chemotherapy doses. These results highlight the promising application of ANPs derived from cockle shells as an effective drug delivery system for a successful chemotherapy against OS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1898-1907, 2019.

Self-Assembled Gold Nanoparticle-Lipid Nanocomposites for On-Demand Delivery, Tumor Accumulation, and Combined Photothermal-Photodynamic Therapy.

In this study, a distinct photoamenable nanoparticle-based drug delivery system was developed for highly efficient targeted on-demand delivery, fluorescence imaging, and therapy by incorporating zinc phthalocyanine (ZnPc) and gold nanoparticles (AuNPs) into liposomes. The hyperthermia, produced by AuNPs under LED light irradiation, enhanced the liquidity of liposomal membrane and promoted the instantaneous release of ZnPc from the carriers realizing the concept of on-demand release. In addition, the local hyperthermia also resulted in thermal damage of cancer cells along with photodynamic effect and achieved a synergetic effect of photodynamic and photothermal therapy. The developed probes showed a high breast cancer carcinoma cells (MCF-7 cell line) inhibition up to 86.7% under red light irradiation. Further, in vivo experiments suggested the high tumor accumulation as well as the antitumor effect in breast tumor-bearing female Sprague-Dawley (SD) rats. The outcomes demonstrate the capability of these probes as a novel drug delivery system to codeliver therapeutic agents with photothermal agents and will have an enormous potential for future diagnosis and therapy.

Thermo- and pH-responsive, Lipid-coated, Mesoporous Silica Nanoparticle-based Dual Drug Delivery System To Improve the Antitumor Effect of Hydrophobic Drugs.

Evodiamine (EVO) and Berberine (BBR), from Euodiae Fructus and Coptidis rhizoma, have been used as an herbal medicine pair in traditional Chinese medicine to exert synergistic antitumor effects against various types of tumor cells. However, their clinical use is limited by their poor solubility and adverse toxic side effects. Mesoporous silica nanoparticles (MSNs) possess excellent properties such as a readily functionalized surface, prominent biocompatibility, and huge specific surface area for loading with hydrophobic and hydrophilic drug. On this basis, a novel temperature- and pH-responsive dual drug delivery platform has been developed, in which lipid-coated MSN@p(NIPAM- co-MA) codelivers EVO and BBR. The results indicate that the nanocarrier improves the efficacy and biocompatibility of the drug pair and maintain desirable drug profiles at the low pH and higher temperature of the tumor microenvironment. The dual drug-loaded MSNs showed excellent synergistic therapy effects in vitro (cytotoxicity, cell migration and invasion, angiogenesis) and in vivo (growth of tumor grafts in mice). Meanwhile, the dual drug-loaded nanoparticles showed lower systemic toxicity than either drug alone, the free drug combination, or Taxol. These results suggest that the temperature- and pH-sensitive lipid-coated MSNs are a promising novel carrier for both hydrophobic and hydrophilic drugs.

Sustained Release Geraniol Nanoparticles Inhibit Human Axillary Odor-Causing Bacteria

Human axillary odor is formed when the skin secretions come into contact with the microflora residing on the skin. The interplay between skin bacteria led to microbial conversion of odorless apocrine sweat into odorous organic acid compounds. Geraniol exhibited significant antimicrobial activity against several human axillary odor-causing bacteria; however, the usage in antiperspirants was limited due to its high volatility. In this study, geraniol nanoparticle was synthesized using dextran as encapsulant to improve its release sustainability. The antimicrobial efficiency of the nanoparticles was also tested on human axillary odor-producing bacteria. The particle size of geraniol nanoparticles ranged from 70 to 110 nm, with an average size of 88 nm while the encapsulation efficiency was 69.24%. The release of geraniol was slow and gradual throughout the experimental period, with no burst release effect. Geraniol was totally entrapped into the interior structure of polymer matrix, and 81.28% of geraniol was released from the nanoparticles in 48 h. The release was plateau on 96 h, following the first order of kinetic. On disk diffusion assay, 6 out of 8 test bacteria were susceptible to geraniol nanoparticles. The inhibitory activity was broad spectrum, as it inhibited both Gram-positive and Gram-negative bacteria. Based on kill curve analysis of Staphylococcus hominis, the bacterial killing capability of geraniol nanoparticles was concentration-dependent. At minimal bactericidal concentration, 99.9% of growth reduction was observed relative to control. In conclusion, an efficient nanoparticle-based geraniol drug delivery system was successfully developed using dextran as encapsulant. The well-regulated drug delivery system enables sustainable release of geraniol to meet the application requirements.

237 - Cell-based analysis of the immune and antioxidant response of the nanocarrier β-cyclodextrin conjugated with cellulose nanocrystals

Cellulose nanocrystals (CNCs) have great potential in many areas of research, applications and future commercialization prospects. Recently, CNCs have emerged as attractive candidates for biomedical applications such as drug and gene delivery systems. Cyclodextrins (CD) are cyclic oligosaccharides with the unique ability to form inclusion complexes with drug molecules and as such, they have been commonly employed as materials in nanoparticle-based drug delivery systems. The conjugation of CNCs with β-CD has been previously reported for drug delivery applications but there are no studies on any potential immunological response of the surface modified CNCs with β-CD. The current study examined the potential immune and antioxidant response induced by CNCs grafted with β-cyclodextrin (CNCs-β-CD) in human monocyte cell line (THP-1) and mouse macrophage-like cell line (J774A.1) We analyzed the secretion of the pro-inflammatory cytokine, interleukin 1β (IL-1β), by ELISA and mitochondria-derived reactive oxygen species (ROS) using fluorescence cell imaging as well as examining examined the intracellular levels of proteins involved in the immune and antioxidant response by immunoblotting. Our results indicated neither a dramatic increase in the IL-1β secretion nor in the mitochondria derived ROS. We also observed no changes in the intracellular antioxidant response in THP-1 cells treated with different concentrations of CNCs-β-CD. Overall, CNCs-β-CD is non-immunogenic and does not induce an increased antioxidant response under the conditions tested and hence has the potential to be used as a drug delivery carrier.

Pluronic F127/Pluronic P123/vitamin E TPGS mixed micelles for oral delivery of mangiferin and quercetin: Mixture-design optimization, micellization, and solubilization behavior

Mixed micelles (MMs) of Pluronic F127 (F127), Pluronic P123 (P123), and Vitamin E TPGS (TPGS) copolymers were prepared by the thin-film sonication method to encapsulate two phenolics with different polarities: magniferin (MGF) and quercetin (QCT). Mixture design was applied for the multi-response optimization of formulations of MGF-loaded MMs (MGF-MMs) and QCT-loaded MMs (QCT-MMs) with high encapsulation efficiency (EE) and drug loading (DL), but low critical micelle concentration (CMC). The optimal mass fractions of F127/P123/TPGS were 0.120/0.328/0.552 for MFG-MMs and 0.131/0.869/0.000 for QCT-MMs, providing EE (>95% (w/w)) and DL (>4.5% (w/w)) higher than those obtained by their individual copolymer components. The CMCs of MFG/QCT-MMs, detected by dynamic light scattering (DLS), were 0.009 ± 0.001 and 0.011 ± 0.001% (w/v), respectively, slightly lower than those obtained by profile analysis tensiometry (PAT). The results revealed that the PAT-CMC represented complete MM formation, while the DLS-CMC detected mono-molecular micelles. The MGF/QCT-MMs showed spherical morphology with diameters of 14.26 ± 0.52 and 21.50 ± 0.37 nm, and their zeta-potentials were −2.89 ± 1.70 and −3.22 ± 1.92 mV, respectively. Nuclear overhauser effect spectroscopy showed that MGF located in both hydrophilic and hydrophobic parts of MMs by orienting its xanthone backbone towards the core, but its glucoside close to the corona. QCT was preferentially located in the PPO core. Both MGF/QCT-MMs had excellent dissolution ability and sustained release in the simulated gastrointestinal environment. This study demonstrated that mixture design was successfully applied for multi-response optimization MM formulations of MGF and QCT, and the developed MMs had potential application as nanoparticle-based drug delivery systems.

Nanoparticles for postinfarct ventricular remodeling.

In recent years, tremendous progress has been made in the treatment of acute myocardial infarction, but pathological ventricular remodeling often causes survivors to suffer from fatal heart failure. Currently, there is no effective therapy to attenuate ventricular remodeling. Recently, nanoparticle-based drug delivery systems are widely applied in biomedicine especially in cancer and liver fibrosis, owing to its excellent physical, chemical and biological properties. Therefore, the use of nanoparticles as delivery vehicles of small molecules, polypeptides, etc. to improve postinfarct ventricular remodeling is expected. In this review, we summarize the updated researches in this fast-growing area and suggest further works needed.

The Application of Nanoparticle-Based Drug Delivery Systems in Checkpoint Blockade Cancer Immunotherapy.

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment.

Targeting chemo-proton therapy on C6 cell line using superparamagnetic iron oxide nanoparticles conjugated with folate and paclitaxel

Purpose: This report presents novel nanoparticle-based drug delivery system (NPDDS) aiming to targeting chemo-proton therapy (TCPT) to improve the therapeutic efficacy on brain cancer treatments.Materials and methods: A NPDDS, superparamagnetic iron oxide nanoparticles conjugated with folate and paclitaxel, was synthesized and applied to C6 brain cancer cell line that was prepared for TCPT. The characterization of NPDDS was analyzed by transmission electron microscope (TEM) and Fourier transform infrared (FTIR) spectroscopy. The uptake of NPDDS into the cytoplasm of C6 cells was observed by confocal laser scanning microscopy (CLSM). The therapeutic efficacy of proton beam was quantitatively evaluated by flow cytometry and clonogenic assay at various radiation dose.Results: NPDDS was synthesized in the uniform size distribution with a mean diameter of 5.44 ± 0.70 nm, and it showed no significant cytotoxicity at the concentration lower than 200 ng/mL. Radiosensitization enhancement factors of PTX, D-SPIONs and FA-PTX-D-SPIONs were 1.35, 1.16 and 1.52, respectively.Conclusions: It was demonstrated that TCPT improved the therapeutic efficacy of the proton beam therapy when the synthesized novel NPDDS was administrated. The improvement in therapeutic efficacy was achieved by the synergetic effect of drug delivery increased by FA, radiosensitivity increased by PTX and absorption of proton energy increased by SPIONs.

Recent advances in "smart" delivery systems for extended drug release in cancer therapy.

Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, systemic toxicity, narrow therapeutic indices, and poor oral bioavailability. Advances in the field of nanomedicine include “smart” drug delivery, or multiple levels of targeting, and extended-release drug-delivery systems that provide additional methods of overcoming these limitations. More recently, the idea of combining smart drug delivery with extended-release has emerged in hopes of developing highly efficient nanoparticles with improved delivery, bioavailability, and safety profiles. Although functionalized and extended-release drug-delivery systems have been studied extensively, there remain gaps in the literature concerning their application in cancer treatment. We aim to provide an overview of smart and extended-release drug-delivery systems for the delivery of cancer therapies, as well as to introduce innovative advancements in nanoparticle design incorporating these principles. With the growing need for increasingly personalized medicine in cancer treatment, smart extended-release nanoparticles have the potential to enhance chemotherapy delivery, patient adherence, and treatment outcomes in cancer patients.

Aggregation of nanoparticles regulated by mechanical properties of nanoparticle–membrane system

The aggregation of nanoparticles (NPs) on the cell membrane is crucial for the cellular uptake process and has important biological implications in protein–membrane interactions. In this paper, we systematically investigate how the aggregation is regulated by the mechanical properties of the NP–membrane system, including the membrane tension, and the size and shape of the NPs. Results show that when NPs aggregate parallel to the cell membrane, increasing the membrane tension will modulate the membrane-mediated interaction between the NPs from attractive to attractive–repulsive and finally to purely repulsive. In contrast, the membrane-mediated interaction is attractive and independent of the membrane tension when the NPs aggregate to a tubular configuration. For the aggregation of NPs of different sizes, the large-size NP is wrapped to a greater extent than the small-size NP. For the aggregation of nonspherical NPs, low aspect ratio and weak NP–membrane adhesion strength lead to the side-to-side configuration, whereas a system with a high aspect ratio and strong NP–membrane adhesion strength prefers the tip-to-tip configuration. Importantly, NPs of different sizes and anisotropic shapes are found to facilitate the aggregation process by reducing the energy barrier that should be overcome during the aggregation. The results reveal the mechanism of the aggregation of NPs on the cell membrane and provide guidelines to the design of NP-based drug delivery systems.

Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.

Preparation and Evaluation of Multifunctional Autofluorescent Magnetic Nanoparticle–Based Drug Delivery Systems Against Mammary Cancer

The Fe3O4@C@NaYF4:Yb,Er nanocarriers of multifunction were synthesized. The mitoxantrone was selected as model drug, and these nanoparticles have high drug loading (0.63 mg/mg). The temperature of Fe3O4@C@NaYF4:Yb,Er in water reached 60°C with 808 nm irritation (2.5 W/cm2). The cumulative release of these nano drug carriers significantly increased because of the increase in temperature, and the 4T1 cell growth inhibition rates were 59.15%, almost 2.25-fold higher than mitoxantrone group (p <0.05). Because the nanoparticles had autofluorescence under 808 nm irritation, the nanocarriers could be traced in both in vitro and in vivo studies. Based on magnetic field, the fluorescence signal of these nano drug carriers could be observed at tumor region during 2-9 h in vivo study. The nanocarriers with magnetic and 808 nm laser group, tumor growth inhibition rate achieved almost 83.14%. These nanoparticles are an outstanding potential carrier for antitumor drugs, which can improve curative effect for tumor while reducing toxicity.

Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine.

Drug, targeting ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose targeting ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine.

A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems

The ability to rapidly screen drugs and drug delivery systems with a more accurate tumor model to better predict their in vivo performance is of great importance in drug development, because there have been some limitations in currently used tumor models. To address this problem, we developed an in vitro breast tumor model on a chip, composed of a microvessel wall, the extracellular matrix (ECM) and uniformly sized multicellular tumor spheroids (MCTS), for the evaluation of nanoparticle-based drug delivery systems. A carbon dots (CDs)-based drug delivery system was synthesized as a model to evaluate the real-time monitoring ability of the system transport through the endothelium and the penetrability into MCTS with a high spatio-temporal resolution on the established platform. Moreover, a modified 96-well plate was used to hold the microfluidic devices for in situ cytotoxicity assays of the MCTS by a microplate reader. Our findings revealed that the synthesized drug delivery system could be transported across an endothelial monolayer within 3 h and was nontoxic to the cells throughout the experiment. In addition, we demonstrated the capabilities of this model by assessing the delivery and efficacy of the drug delivery system in BT549 and T47D spheroids, two cell lines representative of triple negative breast cancer (TNBC) and non-TNBC, respectively. This microfluidic platform enables evaluation of dynamic transport behavior and in situ cytotoxicity evaluation in one system. The established platform provides a more accurate and low-cost in vitro model for rapid drug screening in pre-clinical studies.

Chick chorioallantoic membrane assay as an in vivo model to study the effect of nanoparticle-based anticancer drugs in ovarian cancer

New therapy development is critically needed for ovarian cancer. We used the chicken egg CAM assay to evaluate efficacy of anticancer drug delivery using recently developed biodegradable PMO (periodic mesoporous organosilica) nanoparticles. Human ovarian cancer cells were transplanted onto the CAM membrane of fertilized eggs, resulting in rapid tumor formation. The tumor closely resembles cancer patient tumor and contains extracellular matrix as well as stromal cells and extensive vasculature. PMO nanoparticles loaded with doxorubicin were injected intravenously into the chicken egg resulting in elimination of the tumor. No significant damage to various organs in the chicken embryo occurred. In contrast, injection of free doxorubicin caused widespread organ damage, even when less amount was administered. The lack of toxic effect of nanoparticle loaded doxorubicin was associated with specific delivery of doxorubicin to the tumor. Furthermore, we observed excellent tumor accumulation of the nanoparticles. Lastly, a tumor could be established in the egg using tumor samples from ovarian cancer patients and that our nanoparticles were effective in eliminating the tumor. These results point to the remarkable efficacy of our nanoparticle based drug delivery system and suggests the value of the chicken egg tumor model for testing novel therapies for ovarian cancer.