Nanomedicine Commons^™

Dietary Intake Of Micro- And Nanoplastics: Potential Adverse Gi Effects On Microbiome, Inflammation, And Neoplasia, Michael Saadeh, Gordon Hong, Sana Rabeeah, Priyata Dutta, Edward C. Oldfield, Iv, David A. Johnson

Department of Medicine Faculty Publications

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. …

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Radiation Induced Vaporization Of Exoskeletal Droplets As Potential X-Ray Acoustic Contrast Agents, Mohamed E. Eldib, William N. Frantz, Mark A. Borden, Ryan Lanning, Moyed Miften, David H. Thomas

Department of Radiation Oncology Faculty Papers

BACKGROUND: In vivo dosimetry is a crucial component of ensuring accurate and safe radiation therapy (RT) delivery, but many existing techniques face challenges such as low signal-to-noise ratio (SNR), which can limit their clinical applicability.

PURPOSE: In this study, we investigate a novel contrast agent sensitive to megavoltage (MV) radiation in vitro, ultimately aiming for in vivo dosimetry.

METHODS: Vaporizable exoskeletal droplets were engineered to phase-change into ultrasound-responsive microbubbles upon exposure to MV photon radiation. These droplets comprised a hydrocarbon (HC) exoskeleton doped with gold nanoparticles (GNPs) surrounding a liquid fluorocarbon (FC) core. Radiation absorbed by the GNPs induced localized …

Synthesis And Characterization Of Multifunctional Cerium Oxide Containing Nanoparticles For Biomedical Applications, Ishaan Patel

Honors Undergraduate Theses

This study presents the synthesis and comprehensive characterization of a novel core-shell nanoparticle composed of a maghemite (γ-Fe₂O₃) core and a europium-doped cerium oxide (EuCNP) shell, developed for potential use in cancer theranostics. Using a co-precipitation method, Fe₂O₃–EuCNP core-shell nanoparticles were synthesized and compared against control samples of CNPs, EuCNPs, and Fe₂O₃. A variety of characterization techniques, including UV-Vis spectroscopy, fluorescence spectroscopy, TEM, XRD, XPS, DLS, TGA, and DSC confirmed the successful synthesis of core-shell architecture and europium doping. Moreover, Fe₂O₃–EuCNPs demonstrating strong colloidal …

Magnetic And Ph-Sensitive Dual Actuation Of Biohybrid Microswimmer Of Targeted Drug Release Suitable For Cancer Cell Microenvironment, Richa Chaturvedi, Yumin Kang, Yunji Eom, Sri Ramulu Torati, Cheolgi Kim

Center for Bioelectronics Publications

The chemotherapeutic agents most frequently used in cancer treatment often have limited effectiveness because of their low specificity for tumors and poor therapeutic performance. In addition to the aforementioned therapeutic challenges the drug delivery carriers conjugated with the drug encounter early detection and elimination from the immune system before arriving at the affected area continues to be a significant research focus among researchers. To address this prevalent issue, an effective approach has been developed that leverages the physiological differences between normal and tumor tissue to enhance the efficacy of anticancer drugs. This drug delivery system is designed based on pH-sensitive …

Understanding Nanoparticle-Liver Interactions In Nanomedicine, Yuxin He, Yifan Wang, Lin Wang, Wen Jiang, Stefan Wilhelm

Faculty, Staff and Student Publications

Introduction: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation.

Areas covered: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions.

Expert opinion: While liver accumulation can hinder nanomedicine safety and …

Using Imaging Modalities To Predict Nanoparticle Distribution And Treatment Efficacy In Solid Tumors: The Growing Role Of Ultrasound, Michaela B. Cooley, Dana Wegierak, Agata A. Exner

Faculty Scholarship

Nanomedicine in oncology has not had the success in clinical impact that was anticipated in the early stages of the field's development. Ideally, nanomedicines selectively accumulate in tumor tissue and reduce systemic side effects compared to traditional chemotherapeutics. However, this has been more successful in preclinical animal models than in humans. The causes of this failure to translate may be related to the intra- and inter-patient heterogeneity of the tumor microenvironment. Predicting whether a patient will respond positively to treatment prior to its initiation, through evaluation of characteristics like nanoparticle extravasation and retention potential in the tumor, may be a …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

Age-Associated Disparity In Phagocytic Clearance Affects The Efficacy Of Cancer Nanotherapeutics, Yifan Wang, Weiye Deng, Daeyong Lee, Long Yan, Yifei Lu, Shiyan Dong, Kristin Huntoon, Abin Antony, Xuefeng Li, Rui Ye, Yan Zhao, Feiyan Zhao, Benjamin R Schrank, Jonghoon Ha, Minjeong Kang, Mingming Yang, Ping Gong, Philip L Lorenzi, Lin Tan, Thomas D Gallup, Sarah K Tang, Zhaogang Yang, Jing Li, Nina N Sanford, Hongmei Wang, Betty Y S Kim, Wen Jiang

Faculty, Staff and Student Publications

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger …

Neuromuscular Polytrauma Pain Is Resolved By Macrophage Cox-2 Nanoimmunomodulation, Ibdanelo Cortez, Caitlyn M Gaffney, Riddhi Vichare, Caitlin V Crelli, Lu Liu, Eric Lee, Jules Edralin, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd

Faculty, Staff and Student Publications

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 …

Nano-Embedded Medical Devices And Delivery Systems In Interventional Radiology, Erin Marie D San Valentin, Allan John R Barcena, Carleigh Klusman, Benjamin Martin, Marites P Melancon

Faculty, Staff and Student Publications

Nanomaterials research has significantly accelerated the development of the field of vascular and interventional radiology. The incorporation of nanoparticles with unique and functional properties in medical devices and delivery systems has paved the way for the creation of novel diagnostic and therapeutic procedures for various clinical disorders. In this review, we discuss the advancements in the field of interventional radiology and the role of nanotechnology in maximizing the benefits and mitigating the disadvantages of interventional radiology theranostic procedures. Several nanomaterials have been studied to improve the efficacy of interventional radiology interventions, reduce the complications associated with medical devices, improve the …

Radiotherapy Reimagined: Integrating Nanomedicines Into Radiotherapy Clinical Trials, Allison N Duross, Jack Phan, Alexander J Lazar, Joshua M Walker, Alexander R Guimaraes, Carole Baas, Sunil Krishnan, Charles R Thomas, Conroy Sun, Alexander F Bagley

Faculty, Staff and Student Publications

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. …

Immunological Conversion Of Solid Tumours Using A Bispecific Nanobioconjugate For Cancer Immunotherapy, Yifei Lu, Kristin Huntoon, Daeyong Lee, Yifan Wang, Jonghoon Ha, Yaqing Qie, Xuefeng Li, Benjamin R Schrank, Shiyan Dong, Thomas D Gallup, Minjeong Kang, Hai Zhao, Yi An, Zhaogang Yang, Jing Li, Betty Y S Kim, Wen Jiang

Faculty, Staff and Student Publications

Solid tumours display a limited response to immunotherapies. By contrast, haematological malignancies exhibit significantly higher response rates to immunotherapies as compared with solid tumours. Among several microenvironmental and biological disparities, the differential expression of unique immune regulatory molecules contributes significantly to the interaction of blood cancer cells with immune cells. The self-ligand receptor of the signalling lymphocytic activation molecule family member 7 (SLAMF7), a molecule that is critical in promoting the body's innate immune cells to detect and engulf cancer cells, is expressed nearly exclusively on the cell surface of haematologic tumours, but not on solid ones. Here we show …

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Photothermal Therapy Improves The Efficacy Of A Mek Inhibitor In Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors., Elizabeth E. Sweeney, Rachel A. Burga, Chaoyang Li, Yuan Zhu, Rohan Fernandes

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate …

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …

Rnai Nanotechnology: A Platform For Sirna Screening And Cancer Gene Therapy, Mayurbhai Ravikant Patel

Seton Hall University Dissertations and Theses (ETDs)

Over the past two decades, advances in RNA structural biology have improved our understanding of the structures and folding properties of naturally occurring RNAs. RNA sequences and structures participate in many specific biological functions, such as those performed by messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), micro RNA (miRNA), short-interfering RNA (siRNA), small nuclear RNA (snRNA) and many others. The noncoding RNAs, such as siRNA, do not express proteins but have been utilized in a wide range of applications, including RNA interference (RNAi) and the regulation of mRNA expression. These important biological functions have been implemented in gene …

Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer

Pharmaceutical Sciences Faculty Publications

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo …

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …

Mdr1 Sirna Loaded Hyaluronic Acid-Based Cd44 Targeted Nanoparticle Systems Circumvent Paclitaxel Resistance In Ovarian Cancer, Xiaoqian Yang, Arun K. Iyer, Amit Singh, Edwin Choy, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of …

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.

Combination Of Sirna-Directed Gene Silencing With Cisplatin Reverses Drug Resistance In Human Non-Small Cell Lung Cancer, Shanthi Ganesh, Arun K. Iyer, Jan Weller, David V. Morrissey, Mansoor M. Amiji

Pharmaceutical Sciences Faculty Publications

One of the most challenging aspects of lung cancer therapy is the rapid acquisition of multidrug-resistant (MDR) phenotype. One effective approach would be to identify and downregulate resistance-causing genes in tumors using small interfering RNAs (siRNAs) to increase the sensitivity of tumor cells to chemotherapeutic challenge. After identifying the overexpressed resistance-related antiapoptotic genes (survivin and bcl-2) in cisplatin-resistant cells, the siRNA sequences were designed and screened to select the most efficacious candidates. Modifications were introduced in them to minimize off-target effects. Subsequently, the combination of siRNA and cisplatin that gave the maximum synergy was identified in resistant cells. We then …

Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Edwin Choy, Francis J. Hornicek, Henry Mankin, Lara Milane, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy.

Methodology/Principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy …

Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis J. Hornicek, Henry Mankin, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …