Magnetic Nanoparticle Migration

Tailoring nanoparticles with chemotherapeutics induce synergistic effect which may be considered as “paradigm shift” in cancer invasion. Heterogeneous perfusion, increased vascular tortuosity, inhomogeneity, and high interstitial fluid pressure impairs nanoparticles in their uptake, accumulation, retention and penetration inside deep-seated tumours. This thereby hampers the delivery of targeting moieties at effective concentrations. Combinatorial treatments assisted with other therapeutics like liposomes, antibodies and mild hyperthermia was constantly emphasized in past to improvise drug-administration and extravasation from tumour microvasculature in tumour interstitium. Under normothermic temperature conditions (34°C-39°C), nanoparticles do not cross vascular wall while mild hyperthermia (40°C-42°C) significantly improves extravasation by dilating the vessels and thereby increase the tumour vascular pore size and reduce interstitial fluid pressure.

We speculate that an increase in diffusion coefficient of nanoparticles may play a significant role to address the unknown mechanisms of nanoparticle migration from regions of higher concentration to regions of low concentration. One of the possible reasons of nanoparticle migration is attributed to the fact that the dead cells release intracellular solution after the rupturing of cell membrane. This resultant heat induced thermal cell-damage i.e. necrosis or apoptosis phenomenon thus results in an increase in tumour porosity. It well supports the initial hypothesis that the thermal damage induce enhancement in porosity and diffusion coefficient may play significant roles in particle migration. It also agree with previous experimental studies which suggests that mild hyperthermia helps in vasodilation of vessels in tumour and thus apoptosis or necrosis-mediated nanoparticle diffusion thereby increased penetration depths in tumour and enhances the efficacy of magnetic nanoparticle induced hyperthermia with effective treatment outcomes.