Surgery, chemotherapy and radiotherapy are currently the most used strategies in the treatment of cancer, a disease whose worldwide incidence and mortality is increasing considerably over projections being expected 27.5 million new cases of cancer each year by 2040 (61.7% increase from 2018). Recent investigations on cancer treatment gravitate towards the
use of alternative therapies that overcome the problem of classical ones viz. insufficient concentration of the drug at the
tumor site, limited biodistribution, systemic toxicity, lack of selectivity or differentiation between cancer and normal
cells, and development of cancer therapy resistance.
In this sense, the use of nanobased therapeutic agents has been shown to be advantageous for exploiting the well-known
enhanced permeability and retention (EPR) effect that provokes the accumulation of particulates (bigger than 40 kDa) at
the tumor site. This is due to a combination of fenestration in the vasculature and poor lymphatic drainage from tumors.
Nevertheless, nanoparticles cannot avoid non-selective distribution even though being functionalized with targeting
molecules to induce an improvement of their therapeutic efficacy by increasing their specific uptake by tumoral cells.
To overcome the limitations of passive and active targeting in achieving consistent delivery to a varied clinical target,
more inclusive targeting strategies are being studied that do not relay on the fixed, passive accumulation capacity inherent
to a given tumor. These strategies aim to improve the delivery of nanomedicines across many solid tumor phenotypes,
thereby maximizing their clinical applicability by exploiting the use of remote stimuli responsive nanocarriers to
complement the EPR effect. In this sense, the ability of magnetic nanoparticles (MNPs) to respond to the application of
alternating magnetic fields (AMF) by locally converting magnetic field energy into thermal energy is being used as
external stimulus to gain control both in space and time of cancer therapy. The use of AMF to trigger temperature gradients
at a length scale of few tens of nanometers from the surface of MNPs has advantages compared to the use of light due
to its higher tissue penetration into soft tissues (generally >1m at field frequencies <1kHz for AMF versus few centimetres
for NIR light). In this regard, during this talk we would focus on describing complementary strategies triggered by
magnetic heatin that we have developed to gain spatio-temporal control over i) direct killing of cancer cells, ii) modulation
of the tumour stroma, and iii) drug delivery.