Nano delivers big: designing molecular missiles for cancer therapeutics

Abstract

Current first-line treatments for most cancers feature a short-list of highly potent and often target-blind interventions, including chemotherapy, radiation, and surgical excision. These treatments wreak considerable havoc upon non-cancerous tissue and organs, resulting in deleterious and sometimes fatal side effects for the patient. In response, this past decade has witnessed the robust emergence of nanoparticles and, more relevantly, nanoparticle drug delivery systems (DDS), widely touted as the panacea of cancer therapeutics. While not a cure, nanoparticle DDS can successfully negotiate the clinical payoff between drug dosage and side effects by encompassing target-specific drug delivery strategies. The expanding library of nanoparticles includes lipoproteins, liposomes, dendrimers, polymers, metal and metal oxide nano-spheres and -rods, and carbon nanotubes, so do the modes of delivery. Importantly, however, the pharmaco-dynamics and -kinetics of these nano-complexes remain an urgent issue and a serious bottleneck in the transition from bench to bedside. This review addresses the rise of nanoparticle DDS platforms for cancer and explores concepts of gene/drug delivery and cytotoxicity in pre-clinical and clinical contexts.

Figure 1.

Laser activation of carbon black creates membrane perforation. (A) Femtosecond laser pulses applied to cells incubated with foreign DNA/carbon black. (B) Laser activation generates small acoustic shock-waves which disrupt the cellular membrane and create holes. (C) DNA is now able to traverse the cell membrane.

Figure 2.

Active versus passive targeting in nanoparticle localization. Active Targeting (left): Ligand (antibody/peptide) driven localization, relying upon cancer surface receptor (CSR) mediated endocytosis. Passive Targeting (right): Enhanced permeability and retention (EPR) driven cellular localization, relying upon fluid endocytosis.

Figure 3.

EGF directed killing of cancer cells using single walled carbon nanotube (SWCNT)-cisplatin delivery vector. Nanotubes coated with EGF ligand bind to the cognate EGF receptor on the cancer cell surface and internalize via receptor-mediated endocytosis. Quantum dot nanoparticles (Qdots) allow detection of the nanotubes.