Volume 4, Issue 2-4

The identification of so-called cancer stem cells (CSCs) has sustainably changed our views on cancer by adding hierarchical principles, where tumor cells emerge from a founder population similar to steady-state regenerative processes in normal tissues. The rare founder population of CSCs is thought to be responsible for the recurrence of treatment-resistant tumors and metastatic spread and thus has been declared as the number one target for the next generation of anti-cancer drugs. Here, we will review the state of the art in research on breast cancer stem cells (BCSCs), for which a huge amount of data has accumulated in the past few years. Initial studies have suggested that the CD44+/CD24- profile and epithelial-to-mesenchymal transition (EMT) are associated with BCSCs, which has resulted in the recent identification of first compounds with BCSC-eliminating properties. In this early phase, however, it remains mostly unclear, to which extent these new compounds may exert toxicity to normal stem cells, since a substantial part targets molecular pathways critical for normal stem cell function. Moreover, these new drugs often require combination with conventional chemotherapeutics potentially posing new challenges to nanomedicine in circumventing toxicity and enabling targeted delivery. Most recent data further suggests that normal breast cancer cells might be able to re-create BCSCs and that additional, yet undiscovered kinds of BCSCs may exist. This points to future escape mechanisms. As a consequence, another broad future field of nanomedicine might be finding new drugs via systematic screening approaches. Collectively, this area provides ample possibilities for both traditional and novel nanomedical approaches.

Over the last decade, the emerging field of nanomedicine has undergone rapid progresses. Different internal and external stimuli like pH, temperature, radiation, ultrasound or light have been introduced to expand the diagnostic and therapeutic options of various applications within the field. This review focuses on the novel application of light in the field of nanomedicine as a mechanism to control drug delivery, release and biochemical and genetic functionality at the target. The field of functional nanomaterials for medicine, and in particular of light responsive nanocarriers, polymers and biomolecules offer new therapeutic options but also requires substantial further research to render this approach broadly applicable in clinical practice.

Eradication of HIV requires the clearance of latently infected cells that remained in the reservoirs after highly active antiretroviral therapy (HAART). DermaVir is the first nanomedicine that induces long-lasting cytotoxic T cells (CTL) capable to kill these HIV-infected cells. DermaVir is a synthetic “pathogen-like” nanomedicine mimicking the size, shape, surface properties, cellular entry, endosomal escape, and antigen expression features of pathogens (e.g., viruses). We can optimize the biological activity of DermaVir during the manufacturing processes by controlling the physico-chemical properties of the nanoparticles that influence its structure and intracellular mode-of-action. In the clinic, targeted delivery of DermaVir to epidermal Langerhans cells is achieved with the DermaPrep medical device. Three clinical trials consistently demonstrated long-lasting CTL induced by DermaVir in HIV-infected people and killing of HIV-infected cells compared to Placebo. Since HAART and DermaVir are complementary, we envision that their combination might be suitable to achieve the cure: HAART to potent viral load suppression and DermaVir to kill latently infected cells that get activated to produce HIV.

The active targeting approach has been widely employed to improve nanoparticle drug delivery. Contrary to popular conceptions, attachment of a targeting ligand to a nanopaticle does not alter its biodistribution, but only increases its internalization by target cells. Despite its potential, this strategy has drawbacks that can negate efficacy against tumors. Specifically, compared to non-targeted nanoparticles, a number of active targeting nanoparticles have decreased blood circulation time due to non-specific binding or immunogenicity, reduced tumor penetration, and high susceptibility to lysosomal degradation after internalization. In order to maximize the advantages and overcome the disadvantages, the active targeting approach is best suited for delivering membrane impermeable drugs to targets directly exposed to i.v. injected nanoparticles, such as those in circulation or in the luminal site of tumor vasculatures.