The seminar will take place at 11h00, the 26h of november 2015, in the ENSCBP Amphitheater (Bldg B, Allée Geoffroy Saint Hilaire, Pessac).
Nanoparticles are frequently suggested as diagnostic and therapeutic agents. In this talk, it will be critically discussed for which indications nanoparticles are suited, and where small molecules or microparticles may perform better. Considering basic properties of nanoparticles, the following characteristics exist:
Longer circulation times than most small molecules
High uptake by the reticuloendothelial system (RES)
Accumulation via enhanced permeability and retention (EPR) effects
These characteristics motivate the use of nanoparticles for diagnostic and therapeutic agents that target phagocyting cells. Target organs include liver and lymph nodes but also macrophage-rich pathologies like atherosclerotic plaques. Since nanoparticle-based imaging agents can be very effective and since the persistence of nanoparticles inside cells can be very long, they are also favorably suited for ex vivo labelling of cells and of tissue-engineered transplants, to follow their fate after transplantation.
In addition, the EPR-based accumulation in tumors justifies nanoparticles as carriers of anticancer drugs and as theranostics for personalizing antitumor nanomedicine. In this context, rendering nanoparticles target-specific is not always beneficial since functionalization can reduce the blood circulation time and thus the EPR effect. However, the EPR effect may be stronger than the specific targeting effect (or may even be precondition for the delivery of the drug to the target). As a consequence, the tumor accumulation of a targeted drug may be lower than of the untargeted one.
Further indications result from the long circulation time of nanoparticles. Diagnostically, they may be used as angiography agents or for dynamic contrast enhanced scans. Therapeutically, the long circulation times facilitate their use for (triggered) drug release systems, e.g. thermosensitive liposomes.
Often nanoparticles are recommended for molecularly targeted imaging. However, this application is difficult due to several reasons: long circulation time, EPR effect and RES uptake generate significant unspecific background signals. Also a fast exchange of the unbound fraction between different tissue compartments is not given and there are often safety concerns due to long intracorporal persistence. It should be noted that this is very different for microparticles used for molecular ultrasound imaging. Their large size ensures intravascular persistence and the life time of circulating microbubbles is slow. As a consequence, there is minor unspecific accumulation rendering these agents highly suited for addressing intravascular molecular imaging.
The discussed aspects are related to the basic pharmacological properties of nanoparticles and not all important individual demands on nanoparticles can be addressed in detail such as biocompatibility, degradability, imaging properties, large-scale production, costs and market potential. Rather, it is the intention provide guidance in finding realistic application fields of nanomedicines and in identifying questionable mainstream ideas.