PharmTech spoke to Robert Langer, professor at the Massachusetts Institute of Technology and founder of BIND Biosciences; Stephen Zale,
vice-president of development at BIND Biosciences; and Yanli Zhao, assistant professor and national research foundation fellow
at Nanyang Technological University, Singapore, about engineering nanoparticles with optimal properties for use in cancer
Nanoparticles have significantly changed the scientific landscape of disease treatment, prevention, and diagnosis, generating
a new wave of nanoscale drug-delivery strategies. From solubility/bioavailability enhancement (1, 2) and targeted drug delivery
(3, 4) to controlled/sustained release (5, 6) and protection of labile molecules (e.g., proteins, peptides, and DNA) from
enzymatic degradation (7, 8), these structures can be manufactured, controlled, and manipulated to take on novel properties
and functions that have opened new doors in the biomedical arena.
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While nanoparticles may vary in size ranging from 10 nm to 1000 nm, nanomedicines are typically less than 200 nm (9). Nanoparticles
made from natural or synthetic polymers have gained popularity because of their stability and ease of surface modification.
They can be engineered to achieve controlled drug release as well as specific localization at disease sites by modification
of the polymer characteristics and surface chemistry. For example, it has been well established that nanoparticles accumulate
preferentially at tumor and inflammatory sites due to the enhanced permeability and retention effect (EPR) of the vasculature
(9–11). At the target site, the biodegrable polymeric nanoparticles can act as a local drug depot that provides continuous
release of the encapsulated therapeutic agent.
These advantages offered by nano-particles for targeted drug delivery are a result of their small size and the use of biodegradable
materials. The small size enables the nanoparticles to overcome biological barriers (e.g., gastro-intestinal epithelium, tumor
vasculatures, and endothelium of inflammatory sites) and achieve cellular uptake while the use of biodegradable materials
allows for sustained drug release at the target site (9–11).
Advances in the development of nanoparticles have seen these systems being translated into clinically useful medicines, particularly
in the treatment of cancer. Examples of nanoparticle-based medicines approved by FDA and EMA as cancer therapies include Doxil
and Myocet (liposomal formulations of doxorubicin), DepoCyt (liposomal cytarabine), Dauno-Xome (liposomal daunorubicin), Abraxane
(an albumin-bound formulation of paclitaxel), and Genexol-PM (a polymeric-micelle formulation of paclitaxel).