In Vitro and In Vivo evaluation of a novel folate-targeted theranostic nanoemulsion of docetaxel for imaging and improved anticancer activity against ovarian cancers.

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.

Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification.

Hypoxia-Responsive Copolymer for siRNA Delivery.

A wide variety of nanomedicine has been designed for cancer therapy. Herein, we describe the synthesis and evaluation of a hypoxia-responsive copolymer for siRNA delivery (Perche et al., Angew Chem Int Ed Engl 53:3362-3366, 2014).

Cancer cell spheroids for screening of chemotherapeutics and drug-delivery systems.

Over the last few decades, the most popular platform to perform high-throughput screening for viable anti-neoplastic compounds has been monolayer cell culture. However, cells in monolayer culture lose many of their in vivo characteristics. As a result, this platform provides a limited predictive value in determining the clinical outcome of the compounds of interest.

EGFR Targeted Theranostic Nanoemulsion for Image-Guided Ovarian Cancer Therapy.

Purpose: Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide.

Formulation development of a novel targeted theranostic nanoemulsion of docetaxel to overcome multidrug resistance in ovarian cancer.

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.

Development of EGFR-targeted nanoemulsion for imaging and novel platinum therapy of ovarian cancer.

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, C6-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.

Transferrin-targeted polymeric micelles co-loaded with curcumin and paclitaxel: efficient killing of paclitaxel-resistant cancer cells.

Purpose: The ability to successfully treat advanced forms of cancer remains a challenge due to chemotherapy resistance. Numerous studies indicate that NF-κB, a protein complex that controls the expression of numerous genes, as being a key factor in producing chemo-resistant tumors. In this study, the therapeutic potential of transferrin (TF)-targeted mixed micelles, made of PEG-PE and vitamin E co-loaded with curcumin (CUR), a potent NF-κB inhibitor, and paclitaxel (PCL), was examined.

Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer.

The therapeutic potential of mixed micelles, made of PEG-PE and vitamin E co-loaded with curcumin and paclitaxel, was investigated against SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3-paclitaxel-resistant (TR) cells in vitro and in vivo. The addition of curcumin at various concentrations did not significantly enhance the cytotoxicity of paclitaxel against SK-OV-3 in vitro. However, a clear synergistic effect was observed with the combination treatment against SK-OV-3TR in vitro.

Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded with curcumin and doxorubicin.

Background: Treatment of late stage cancers has proven to be a very difficult task. Targeted therapy and combinatory drug administration may be the solution.

Purpose: The study was performed to evaluate the therapeutic efficacy of PEG-PE micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against HCT-116 human colorectal adenocarcinoma cells both in vitro and in vivo.

Nanopreparations to overcome multidrug resistance in cancer.

Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery.

Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model.

We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an advanced clinical stage and develop resistance to standard of care platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had limited benefits in refractory patients.

Reversal of multidrug resistance by co-delivery of tariquidar (XR9576) and paclitaxel using long-circulating liposomes.

One of the major obstacles to the success of cancer chemotherapy is the multidrug resistance (MDR) often resulting due to the overexpression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results in overcoming the MDR. However, P-gp is also expressed in normal tissues like blood brain barrier, gastrointestinal track, liver, spleen and kidney.

Mitochondria-targeted liposomes improve the apoptotic and cytotoxic action of sclareol.

Current efforts toward improving the effectiveness of drug therapy are increasingly relying on drug-targeting strategies to effectively deliver bioactive molecules to their molecular targets. Pharmaceutical nanocarriers represent a major tool toward this aim, and our efforts have been directed toward achieving nanocarrier-mediated subcellular delivery of drug molecules with mitochondria as the primary subcellular target. Meeting the need for specific subcellular delivery is essential to realizing the full potential of many poorly soluble anticancer drugs.