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Muscle atrophy occurs during chronic diseases, resulting in diminished quality of life and compromised treatment outcomes. There is a high demand for therapeutics that increase muscle mass while abrogating the need for special dietary and exercise requirements. Therefore, we developed an efficient nanomedicine approach capable of increasing muscle mass. Methods: The therapy is based on nanoparticle-mediated delivery of follistatin messenger RNA (mRNA) to the liver after subcutaneous administration. The delivered mRNA directs hepatic cellular machinery to produce follistatin, a glycoprotein that increases lean mass through inhibition of negative regulators of muscle mass (myostatin and activin A). These factors are elevated in numerous disease states, thereby providing a target for therapeutic intervention. Results: Animal studies validated that mRNA-loaded nanoparticles enter systemic circulation following subcutaneous injection, accumulate and internalize in the liver, where the mRNA is translated into follistatin. Follistatin serum levels were elevated for 72 h post injection and efficiently reduced activin A and myostatin serum concentrations. After eight weeks of repeated injections, the lean mass of mice in the treatment group was ~10% higher when compared to that of the controls. Conclusion: Based on the obtained results demonstrating an increased muscle mass as well as restricted fat accumulation, this nanoplatform might be a milestone in the development of mRNA technologies and the treatment of muscle wasting disorders.

Cancer has remained one of the most indomitable conundrums for scientists over centuries due to its multifarious etiology. While improved therapeutic and diagnostic approaches have commendably augmented the rate of survival of cancer patients, a holistic riddance from the ailment is still implausible. Hence, further explorations to scout for novel strategies of cancer therapy and diagnosis are necessary. Theranostics (amalgamation of therapy and diagnostics) has emerged as one of the avant-garde strategies, which provides a two-pronged advantage in cancer management. This integrative approach has found immense relevance in light of nanotechnology. Nanoparticles can be customized (loaded with a mélange of therapeutic drugs and diagnostic probes) to develop theranostic properties, thereby constructing nanotheranostic agents. These nano-composites are lucrative tools for cancer cell obliteration and simultaneous monitoring of the drug action, and can also be tailored for targeted drug delivery. Nanotheranostic agents have emerged as a prudent ploy for synchronized cancer intervention and detection of the 'route and reach' of the drugs. In this review, we discuss the diversified state-of-the-art facets of theranostic nanoparticles, including various nanoparticle-based platforms as well as the plethora of reported therapeutic drugs, aptamers, markers and diagnostic molecules that have found use in the precincts of nanotheranostics.

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks.

Targeted delivery of therapeutic and diagnostic agents to cancer sites has significant potential to improve the therapeutic outcome of treatment while minimizing severe side effects. It is widely accepted that decoration of the drug delivery systems with targeting ligands that bind specifically to the receptors on the cancer cells is a promising strategy that may substantially enhance accumulation of anticancer agents in the tumors. Due to the transformed cellular nature, cancer cells exhibit a variety of overexpressed cell surface receptors for peptides, hormones, and essential nutrients, providing a significant number of target candidates for selective drug delivery. Among others, luteinizing hormone-releasing hormone (LHRH) receptors are overexpressed in the majority of cancers, while their expression in healthy tissues, apart from pituitary cells, is limited. The recent studies indicate that LHRH peptides can be employed to efficiently guide anticancer and imaging agents directly to cancerous cells, thereby increasing the amount of these substances in tumor tissue and preventing normal cells from unnecessary exposure. This manuscript provides an overview of the targeted drug delivery platforms that take advantage of the LHRH receptors overexpression by cancer cells.

This study represents a novel approach for intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. To assess the potential of the developed therapy, dendrimer-based nanoplatforms for cancer-targeted delivery of near-infrared photosensitizer, phthalocyanine, and DJ-1 siRNA have been constructed. In vitro studies revealed that therapeutic efficacy of the combinatorial approach was enhanced when compared to PDT alone and this enhancement was more pronounced in ovarian carcinoma cells, which are characterized by higher basal levels of DJ-1 protein. Moreover, the ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence. Thus, the developed therapeutic approach can be potentially employed intraoperatively to eradicate unresactable cancer cells.The complete clearance of microscopic residual tumor cells during excision surgery is important to improve survival of the patient. In this interesting paper, the authors developed a novel approach using targeted photodynamic therapy (PDT), combining a photosensitizer, phthalocyanine, and DJ-1 siRNA for the treatment of ovarian cancer. The data showed that this approach increased cancer cell killing and may pave way for future clinical studies.

PURPOSE: Surgery plays a decisive role in cancer treatment and patient prognosis is closely linked to the size of residual tumors after cytoreduction. Even with the best surgical techniques, however, palpation and visual inspection do not always permit discrimination between malignant and normal tissue types and can lead to incomplete cancer resection. It is extremely important, therefore, to improve tumor delineation during surgery and provide efficient adjuvant treatment intraoperatively, to further eliminate occult disease sites that may be left behind. Among the explored fluorescent agents, near infrared (NIR, 750 – 900 nm) fluorescent imaging agents possess advantages of deep tissue penetration and minimal tissue autofluorescence and light scattering, making them promising candidates for optical imaging guided cancer debulking surgery. Our study is aimed to develop a nanomedicine capable of maximizing selective tumor detection via fluorescence imaging and immediate phototherapy for tumor tissue eradication. METHODS: To develop an effective theranostic probe, silicon naphthalocyanine (SiNc) with strong light absorption in the NIR region was loaded into a biodegradable polymeric nanoparticle based on the amphiphilic block polymer, poly (ethylene glycol)–poly(ε–caprolactone) (PEG–PCL). Such a design has provided a possibility to control and improve fluorescence and phototherapeutic properties of the SiNc–based theranostic agent. RESULTS: As a theranostic agent, the developed SiNc polymeric nanoparticles were evaluated by DLS, TEM (around 20 nm), NIR absorbance and fluorescence spectroscopies, ROS and hyperthermia production. The safety and effectiveness of SiNc–nanoparticles as a bioimaging agent was confirm in vitro and in vivo. In addition, high photostability of SiNc–nanoparticles have been detected. The efficiency of SiNc–nanoparticles as an NIR bioimaging agent was confirmed by recording the strong fluorescence signal in the ovarian cancer tumors. The in vitro and in vivo studies demonstrated that, after efficient tumor accumulation via i.v. administration, phototherapy mediated by SiNc can efficiently destroy ovarian cancer tumors. CONCLUSIONS: We have developed a photostable NIR theranostic nanomedicine platform that provides florescence detection of subcutaneous and orthotopic tumor xenographs as well as effective phototherapy resulting in complete tumor eradication. This theranostic agent can be potentially employed concurrently for tumor delineation with real–time NIR fluorescence signal during surgery and intraoperative targeted treatment to further eliminate non–surgically removable disease sites by non–toxic phototherapy. Citation Format: Oleh Taratula, Olena Taratula, Xiaoning Li, Canan Schumann, Shay Bracha, Milan Milovancev, Adam W. G. Alani. THERANOSTIC NANOPLATFORM FOR IMAGE–GUIDED SURGERY AND INTRAOPERATIVE PHOTOTHERAPY FOR OVARIAN CANCER TREATMENT [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-012.

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40 °C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach.