Current Topics in Medicinal Chemistry - Volume 15, Issue 15, 2015

The article is an up-to-date review of the state-of-the art in the challenging field of smart synthetic polymer nanocarriers, presenting the most relevant achievements in the area, with a special emphasis on the outstanding potential of these nanovehicles to be used as multifunctional devices capable to deliver their cargo to a specific targeted area in the human body and to release it in a well controlled fashion. Stimuli-responsive nano drug delivery systems are presented according to a classification that takes into account the endogenous or exogenous nature of the stimuli. Each category is amply illustrated by carefully selected examples of the most impressive achievements. The endogenous stimuli category is fully described by presentation of pH, redox potential, and enzyme-responsive nanocarriers. From the category of exogenous stimuliresponsive nanomaterials, we focused our attention on temperature, light and magnetic sensitive nanocarriers.

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed.

Mesoporous materials synthesized in the presence of templates, are commonly used for environment and medical applications. Due to the properties it holds, mesoporous silica nanoparticles is an excellent material for use in medical field, biomaterials, active principles delivery systems, enzyme immobilization and imaging. Their structure allows embedding large and small molecules, DNA adsorption and genetic transfer. Using mesoporous silica nanoparticles for delivery of bioactive molecules can protect them against degradation under physiological conditions, allow controlled drugs release and minimize side effects on healthy tissues. Cellular tests performed on mesoporous silica nanoparticles demonstrate that MSN's cytotoxicity is dependent on the size and concentration and suggests the use of larger size nanoparticles is optimal for medical applications. Mesoporous materials possess high biological compatibility, are non-toxic and can be easily modified by functionalizing the surface or inside the pores by grafting or co-condensation method. The structure, composition and pores size of this material can be optimized during synthesis by varying the stoichiometric reactants, reaction conditions, nature of the template’s molecules or by functionalization method.

An implantable system for drug delivery provides a new strategy for drug therapy, and typically involves a microfluidic chip produced with micro or nano-technology. Implantable systems have the flexibility to conform various schemes of drug release, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Such an implantable system is classified as allowing either controllable or uncontrollable drug release after implantation, so an active or passive delivery system respectively. The performance and related applications of these systems vary. The key points of each technology are highlighted such as performance, working principle, fabrication methods, and dimensional constrains. We here review the implantable drug-delivery system in current research with a focus on application and chip performance, and comparison for passive and active delivery system.

Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nanocarriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or sideeffects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced.

The attention for gold nanoparticles (AuNPs) has recently grown, especially regarding its applications in biomedicine, like cancer treatment and immunization by nano-vaccines. The interest for this type of nanoparticles is given by their ability to penetrate blood vessels and tissue barriers and to be targeted to a specific cell by means of specifically functionalized molecules. Moreover, AuNPs posses special properties which make them useful in concomitant diagnostic by medical imaging and tumor ablation by means of photothermal activation.

Metastasis is the cause of most cancer mortality. Circulating tumour cells (CTC) are cells that are released from a primary tumour into the bloodstream and that are considered to act as the main promoters of metastasis. These cells are therefore targets for the understanding of tumour biology and an improvement of clinical management of the disease. Early detection of CTC and analysis of their cell surface markers provide critical information for the diagnosis of cancer and its target therapy. CTC are shed into the bloodstream as tumours grow, and are believed to initiate the spread of cancer. The identification and analysis of CTC is thus an important objective for the development of noninvasive cancer diagnosis. Methods of capture and detection of CTC have been complicated and costly, and the captured cells could not be cultured and expanded directly. Because CTC are rare, existing as only a few per one billion blood cells, a highly efficient method is required to capture and to culture CTC for further assay. Chipbased and traditional methods have emerged to isolate, to detect and to characterize CTC. As CTC are a rare event, their investigation requires multidisciplinary considerations of both biological and physical properties. Chip-based biosensor platforms are being introduced into the technology for the quantification of CTC with promising results. This review describes recent progress in the identification of CTC; the approach developed has a simple workflow and scalable multiplexing, which makes it ideal for further investigation of CTC biomarkers.