EGFR Targeted Theranostic Nanoemulsion for Image-Guided Ovarian Cancer Therapy (original) (raw)
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Development of EGFR-Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer
Pharmaceutical Research, 2014
Purpose Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C 6 -ceramide, were designed to overcome these limitations. Methods The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780 CP . Results The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFRtargeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC 50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist ® . Conclusion The myrisplatin/C 6 -ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer.
Multifunctional Nanoemulsion Platform for Imaging Guided Therapy Evaluated in Experimental Cancer
ACS Nano, 2011
Nanoparticle applications in medicine have seen a tremendous growth in the past decade. In addition to their drug targeting application and their ability to improve bioavailability of drugs, nanoparticles can be designed to allow their detection with a variety of imaging methodologies. In the current study, we developed a multimodal nanoparticle platform to enable imaging guided therapy, which was evaluated in a colon cancer mouse model. This "theranostic" platform is based on oil-in-water nanoemulsions and carries iron oxide nanocrystals for MRI, the fluorescent dye Cy7 for NIRF imaging, and the hydrophobic glucocorticoid prednisolone acetate valerate (PAV) for therapeutic purposes. Angiogenesis-targeted nanoemulsions functionalized with Rvβ 3 -specific RGD peptides were evaluated, as well. When subcutaneous tumors were palpable, the nanoemulsions were administered at a dose of 30 mg of FeO/kg and 10 mg of PAV/kg. MRI and NIRF imaging showed significant nanoparticle accumulation in the tumors, while tumor growth profiles revealed a potent inhibitory effect in all of the PAV nanoemulsion-treated animals as compared to the ones treated with control nanoemulsions, the free drug, or saline. This study demonstrated that our nanoemulsions, when loaded with PAV, iron oxide nanocrystals, and Cy7, represent a flexible and unique theranostic nanoparticle platform that can be applied for imaging guided therapy of cancer.
Cancer biology & therapy, 2018
Ovarian cancer ranks fifth in cancer related deaths for women in USA. The high mortality rate associated with ovarian cancer is due to diagnosis at later stages of disease and the high recurrence rate of 60-80%. Recurrent ovarian cancers are more likely to present as multidrug resistance (MDR) leading to unfavorable response from 2 and 3 line chemotherapy. Nanoemulsions (NEs) are emerging as an attractive drug delivery system to overcome MDR challenges. NEs can also minimize exposure of therapeutic cargo to normal tissues potentially reducing side effects. In >80% of ovarian cancers, Folate Receptor-α (FR-α) is expressed at 10- to 100-fold higher levels than on non-pathological tissues. Therefore, folate (FA) is being evaluated as an active targeting moiety for FR-α ovarian cancer. To improve therapeutic outcome with reduced toxicity, we developed NMI-500, a FA targeted gadolinium (Gd) annotated NE loaded with docetaxel (DTX). NMI-500 has been developed as theranostic agents as G...
Integrating Nanotherapeutic Platforms to Image Guided Approaches for Management of Cancer
2020
Cancer is a leading cause of mortality worldwide, accounting for 8.8 million deaths in 2015. The landscape of cancer therapeutics is rapidly advancing with development of new and sophisticated approaches to diagnostic testing. Treatment plan for early diagnosed patients include radiation therapy, tumor ablation, surgery, immunotherapy and chemotherapy. However the treatment can only be initiated when the cancer has been diagnosed thoroughly. Theranostics is a term that combines diagnostics with therapeutics. It embraces multiple techniques to arrive at comprehensive diagnosis, molecular images and an individualized treatment regimen. Recently, there is an effort to tangle the emerging approach with nanotechnologies, in an attempt to develop theranostic nanoplatforms and methodologies. Theranostic approach to management of cancer offers numerous advantages. They are designed to monitor cancer treatment in real time. A wide variety of theranostic nanoplatforms that are based on diverse nanostructures like magnetic nanoparticles, carbon nanotubes, gold nanomaterials, polymeric nanoparticles and silica nanoparticles showed great potential as cancer theranostics. Nano therapeutic platforms have been successful in integrating image guidance with targeted approach to treat cancer.
Applied Biochemistry and Biotechnology, 2011
Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging contrast agents. When used as drug carriers, nanoformulations can increase tumor exposure to therapeutic agents and result in improved treatment effects by prolonging circulation times, protecting entrapped drugs from degradation, and enhancing tumor uptake through the EPR effect as well as receptor-mediated endocytosis. Multiple therapeutic agents such as chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy. Additionally, imaging and therapy agents can be codelivered to provide seamless integration of diagnostics, therapy and follow-up, and different therapeutic modalities such as chemotherapy and hyperthermia can be coadministered to take advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of nanoformulations that can be used as multifunctional platforms for cancer theranostics. Nanomedicine approaches in cancer have great potential for clinically translatable advances that can positively impact the overall diagnostic and therapeutic process, and result in enhanced quality of life for cancer patients. However, a concerted scientific effort is still necessary to fully explore long-term risks, effects, and precautions for safe human use. hyperthermia, immunotherapy, hormone therapy, stem cell therapy, and combinations thereof. In many cases, early detection is the crucial factor that directs the treatment regime and the choice of therapeutic intervention. The stage at which a tumor is detected determines whether it can be surgically resected without need for adjuvant treatment, or whether it will require a combination of approaches, which typically include surgery, radiation, and chemotherapy.
Imaging and therapy of ovarian cancer: clinical application of nanoparticles and future perspectives
Theranostics
Despite significant advances in cancer diagnostics and treatment, ovarian cancers (OC) continue to kill more than 150,000 women every year worldwide. Due to the relatively asymptomatic nature and the advanced stage of the disease at the time of diagnosis, OC is the most lethal gynecologic malignancy. The current treatment for advanced OC relies on the synergistic effect of combining surgical cytoreduction and chemotherapy; however, beside the fact that chemotherapy resistance is a major challenge in OC management, new imaging strategies are needed to target microscopic lesions and improve both cytoreductive surgery and patient outcomes. In this context, nanostructured probes are emerging as a new class of medical tool that can simultaneously provide imaging contrast, target tumor cells, and carry a wide range of medicines resulting in better diagnosis and therapeutic precision. Herein we summarize several exemplary efforts in nanomedicine for addressing unmet clinical needs.
Biodegradable nanoparticles as theranostics of ovarian cancer: an overview
Objectives Above 10 million people are suffering from cancers every year. As per American Cancer Society, more than 22 440 new cases and 14 080 deaths were reported from ovarian cancer yearly worldwide. This review explores the current status, challenges and future perspectives of tumour-targeted theranostic nanoparticles (NPs). Key findings Most of the ovarian malignancy cases are uncovered after the disease is in a difficult state due to poor screening techniques and non-specific symptoms. In this manner, forceful and fruitful treatment is required that will indicate insignificant lethal impacts to solid tissue. In the current research, stealth biodegradable NPs are produced as vehicles for imaging and treatment of ovarian cancer as the controlled and targeted delivery of chemotherapeutic as well as imaging agents. To enhance the dependability of the colloidal suspension as well as to increase their circulation lifetime, NPs are introduced by incorporating the functional poly(ethylene glycol) on their surface, which also provides a site to conjugation of focusing on agents to ovarian tissue. Conclusions Biodegradable theranostic NPs can be fabricated and surface engineered without any alteration in drug-loading capacity, safety and efficacy. These NPs have shown promising results in imaging as well as treatment of ovarian cancer.
Drug Delivery
Objective: Ovarian cancer is a highly lethal disease in which the majority of patients eventually demonstrate multidrug resistance. Develop a novel active targeted theranostic nanomedicine designed to overcome drug efflux mechanisms, using a Generally Regarded As Safe (GRAS) grade nanoemulsion (NE) as a clinically relevant platform. Materials and methods: The NEs surface-functionalized with folate and gadolinium, were made using GRAS grade excipients and a high-shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3 and SKOV3TR. The NE accumulation in tumors was evaluated in SKOV3 tumor-bearing mice by magnetic resonance imaging (MRI). Results and discussion: The NE with particle size 5150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and folatetargeted NEs; improved cytotoxicity was observed for the folate-targeted NEs showing a 270fold drop in the IC 50 in SKOV3TR cells as compared to docetaxel alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist Õ . Folate-targeted NEs accumulated in tumors for prolonged period of time compared to Magnevist Õ and showed enhanced contrast compared to non-targeted NEs with MRI in SKOV3 tumor-bearing mice suggesting active targeting of NEs due to folate modification. Conclusions: A folate-targeted, theranostic NE delivers docetaxel by receptor mediated endocytosis that shows enhanced cytotoxicity capable of overcoming ABC transporter mediated taxane resistance. The diagnostic capability of the targeted nanomedicine showed enhanced contrast in tumors compared to clinically relevant MRI contrast agent Magnevist Õ .
Image-guided nanosystems for targeted delivery in cancer therapy
Current Medicinal Chemistry, 2012
Current challenges in early detection, limitations of conventional treatment options, and the constant evolution of cancer cells with metastatic and multi-drug resistant phenotypes require novel strategies to effectively combat this deadly disease. Nanomedical technologies are evolving at a rapid pace and are poised to play a vital role in diagnostic and therapeutic interventions -the so-called "theranostics" -with potential to advance personalized medicine. In this regard, nanoparticulate delivery systems can be designed with tumor seeking characteristics by utilizing the inherent abnormalities and leaky vasculature of solid tumors or custom engineered with targeting ligands for more specific tumor drug targeting. In this review we discuss some of the recent advances made in the development of multifunctional polymeric nanosystems with an emphasis on image-guided drug and gene delivery. Multifunctional nanosystems incorporate variety of payloads (anticancer drugs and genes), imaging agents (optical probes, radio-ligands, and contrast agents), and targeting ligands (antibodies and peptides) for multi-pronged cancer intervention with potential to report therapeutic outcomes. Through advances in combinatorial polymer synthesis and high-throughput testing methods, rapid progress in novel optical/radiolabeling strategies, and the technological breakthroughs in instrumentation, such as hybrid molecular and functional imaging systems, there is tremendous future potential in clinical utility of theranostic nanosystems.
Nanoparticle-Based Tumor Theranostics with Molecular Imaging
Current Pharmaceutical Biotechnology, 2014
The past few decades have brought on a dramatic change in the treatment of cancer; however, routine treatments fail to specifically clear tumorigenic cells and may be followed by cancer recurrence. Recent advances in developing multifunctional nanoparticles provide exciting new possibilities for drug delivery used in tumor-targeted therapy. Moreover, molecular imaging is an invaluable tool in evaluating new molecular targets, cancer diagnosis, predicting of tumor response to available therapies and monitoring response to therapy as well as developing new drugs prior to clinical translation. Combining of targeted cancer therapy and molecular imaging, termed as image-guided drug delivery, can achieve objectives of noninvasive assessment of drug biodistribution and real-time monitoring of therapeutic responses. Image-guided drug delivery has become an upcoming field with extensive prospect in cancer therapy and may provide an effective platform for personalized cancer care. This review will focus on the significance and recent advances in targeted and traceable therapeutic strategy for cancer therapy.