Volume 8, Issue 1

The rationale for the use of nanoparticle formulations to treat cancer is based on the ability of these particles to facilitate selective delivery of drugs to the tumor site, reducing adverse effects and improving therapeutic outcomes. Current clinically approved nanomedicines have managed to reduce adverse effects significantly but the increase in overall survival is modest in many cases. Therefore, even though the goal of a better quality of life for the cancer patients has been achieved in large part, the increase in life expectancy still remains a critical challenge. Abnormalities in the tumor micro-environment prevent homogeneous distribution of nanoparticles to the interior of the tumor, decreasing the efficacy of the drug. Intelligent drug delivery systems offer new hope for overcoming these physiological barriers posed by the tumor and have the potential to provide more effective treatments. This review discusses the barriers to the delivery of nanomedicines to solid tumors, suggests design considerations that could optimize delivery and reviews promising intelligent drug delivery systems that have been developed to date.

The aim of this work is to study the kinetics of ultrasound (70 kHz) – using a kinetic model that takes into account cavitation events and drug re-encapsulation upon the cessation of the acoustic field. The simulation allowed the determination of three parameters α , β and λ that define the release and re-encapsulation behavior of this drug delivery system (DDS). The results showed that the drug release increased with increasing power density, as evidenced by the correlation between α and power density. The micelle re-assembly, quantified by the parameter β , also increased with increasing power density. The parameter λ , which is associated with the initial phase of the release process, showed a constant value regardless of the power density. The significance of these results was discussed. Additionally, a comparison between these parameters in folate-targeted and non-targeted micelles showed statistically significant differences for several power densities examined. A better understanding of the kinetics involved in this DDS is very important for the determination of the optimum ultrasound parameters to be used in future in vitro and in vivo experiments.

The use of liposomes as carriers for chemotherapeutic agents in combination with ultrasound as a stimulus to control the time and space of the drug release is a promising approach for cancer treatment, as it can reduce the side effects caused by conventional chemotherapy. This in vitro study investigated the triggered release of calcein from stealth (PEGylated) and non-stealth (non-PEGylated) liposomes, using ultrasound at low (20 kHz) and high (1 and 3 MHz) frequencies, and at different power densities. Release was monitored by the increase in fluorescence due to relieving of calcein’s self-quenching upon dilution when the model drug leaks out of the liposomes. The results showed that, independent of the power density, the release was highest at 20 kHz. For the same frequency, release usually increased with increasing power densities. Additionally, for release at 20 kHz, a comparison was done for PEGylated and non-PEGylated liposomes, at two pH values: 5.2 and 7.4. The results were then compared to previously published studies. In all cases, the mechanism of release seems to involve cavitation events that either pierce a hole in or shear open the liposomes, as all the determined power densities are above the transient cavitation threshold.

The 2nd International Conference on Nanotheranostics was successfully organized between October 29th and November 1st 2015 at Limassol, Cyprus. A nanotheranostics conference is an important initiative, expected to provide the forum for idea exchange and create a potential high-impact nanomedicine paradigm. ICoN2015 attracted the contribution of prominent entities in the nanomedicine field and has succeeded in bringing together high-caliber researchers and a promising population of young scientists at the dawn of their careers from all five continents. Major thematic areas included (i) the roadmap of nanotheranostics development in a patient-oriented approach, (ii) emerging challenges for nanotheranostic applications, (iii) nanoscience technologies for theranostic approaches, (iv) an emphasis session on cancer nanotheranostics, and (v) toxicology, regulatory issues and ethics. Recent developments and emerging challenges were elaborated by leading researchers in the field and are summarized in this report.

Nanoparticles with coating entrapping a chemotherapeutic drug for delivery have not been tested for their cytotoxic effects in in-vitro glioblastoma cell cultures to increase treatment efficacy. Therefore, we synthesized silica-coated gold nanorods and gold nanospheres that were loaded with doxorubicin or temozolomide. The morphology of the nanoparticles was characterized using transmission electron microscopy (TEM), the molecular structure was characterized using infrared spectroscopy and in vitro efficacy was determined using glioblastoma cell cultures. TEM analysis showed that gold nanorods had a length of 49–65 nm and a diameter of 8.5–14 nm whereas gold nanospheres had a diameter of 9.5–37 nm. Infrared spectroscopy of doxorubicin and temozolomide and the silica coating revealed molecular fingerprints such as bending, stretching and vibrations of chemical bonds that confirmed the presence of silica coating and drug loading of the gold nanoparticles. In the biological assessment of the effects of drug-loaded gold nanoparticles on primary glioblastoma cell cultures, cytotoxicity, viability and the ratio of cyototoxicity and viability were used as parameters to analyze the effects on the cells of drug delivery via gold nanoparticles on the cells. Our data suggest that doxorubicin in the concentration range of 0.12–3.16 μM when delivered using both gold nanorods and nanospheres induced a 3.8–5.5-fold increased cytotoxicity in comparison to direct delivery. Temozolomide in the concentration range of 4.6–115 μM when delivered by either type of gold nanoparticles induced a 2–4-fold increased cytotoxicity in comparison to direct delivery. Nanospheres were more effective in delivery and cytotoxicity of doxorubicin and temozolomide to glioblastoma cells than gold nanorods. Our data suggest that gold nanoparticles and in particular gold nanospheres are more effective in delivery of doxorubicin and temozolomide to primary glioblastoma cells in culture than direct delivery.

This opinion paper contains views on how organizers of scientific meetings and journal editors can facilitate transfer of new nanomedicine into the clinic. The need for interdisciplinary discussions at such meetings are emphasized, as well as the importance of learning from the regulatory authorities and large pharmaceutical companies about what is needed to bring new products into clinical use. The importance of improving the review process of translational studies published by the main nanomedical journals is pointed out as very important for bringing the field forward and to increase the level of scientific discussions in general.