Smart Cancer Nanotheranostics
(Nanowerk Spotlight) Cancer is one of the leading causes of death in the world and remains a difficult disease to treat. Current problems associated with conventional cancer chemotherapies include insolubility of drugs in aqueous medium; delivery of sub-therapeutic doses to target cells; lack of bioavailability; and most importantly, non-specific toxicity to normal tissues. Recent contributions of nanotechnology research address possible solutions to these conundrums. Nevertheless, challenges remain with respect to delivery to specific sites, real time tracking of the delivery system, and control over the release system after the drug has been transported to the target site.
Nanomedical research on nanoparticles is exploring these issues and has already been showing potential solutions for cancer diagnosis and treatment. But a heterogeneous disease like cancer requires smart approaches where therapeutic and diagnostic platforms are integrated into a theranostic approach.
Theranostics – a combination of the words therapeutics and diagnostics – describes a treatment platform that combines a diagnostic test with targeted therapy based on the test results, i.e. a step towards personalized medicine. Making use of nanotechnology materials and applications, theranostic nanomedicine can be understood as an integrated nanotherapeutic system, which can diagnose, deliver targeted therapy and monitor the response to therapy.
Theranostic nanomedicine has the potential for simultaneous and real time monitoring of drug delivery, trafficking of drug and therapeutic responses.
Our Smart Materials and Biodevice group at the Biosensors and Bioelectronics Centre, Linkoping University, Sweden, has demonstrated for the first time a MRI-visual order-disorder micellar nanostructures for smart cancer theranostics.
The drug release mechanism via functional outcome of the pH response illustrated in the schematic diagram. (Image: Smart Materials and Biodevice group, Linköping University) In the report, we fabricated a novel pH-triggered tumour microenvironment sensitive order-disorder nanomicelle platform for smart theranostic nanomedicine.
The real-time monitoring of drug distribution will help physicians to assess the type and dosage of drug for each patient and thus will prevent overdose that could result in detrimental side-effects, or suboptimal dose that could lead to tumour progression.
Additionally, the monitoring of normal healthy tissues by differentiating with the MRI contrast will help balance the estimation of lethal dose (for normal tissue) and pharmacologically active doses (for tumour). As a result, this will help to minimize off-target effects and enhance effective treatment.
In the present report, the concurrent therapy by doxorubicin and imaging strategies by superparamagnetic iron oxide nanoparticles with our smart architecture will provide every detail and thus can enable stratification of patients into categorized responder (high/medium/low), and has the potential to enhance the clinical outcome of therapy.
It shows, for the first time, concentration dependent T2-weighted MRI contrast for a monolayer of clustered cancer cells. The pH tunable order-disorder transition of the core-shell structure induces the relative changes in MRI that will be sensitive to tumour microenvironment and stages.
A novel MRI visual order-disorder nanostructure for cancer nanomedicine explores pH-trigger mechanism for theranostics of tumour hallmark functions. The pH tunable order-disorder transition induces the relative changes in MRI contrast. The outcome elucidates the potential of this material for smart cancer theranostics by delivering non-invasive real-time diagnosis, targeted therapy and monitoring the course and response of the action. (Image: Smart Materials and Biodevice group, Linköping University)
Our findings illustrate the potential of these biocompatible smart theranostic micellar nanostructures as a nontoxic, tumour-target specific, tumour-microenvironment sensitive, pH-responsive drug delivery system with provision for early stage tumour sensing, tracking and therapy for cells over-expressed with folate receptors.
The outcomes elucidate the potential of smart cancer theranostic nanomedicine in non-invasive real-time diagnosis, targeted therapy and monitoring of the course and response of the action before, during and after treatment regimen.
By Hirak K Patra, Nisar Ul Khali, Thobias Romu, Emilia Wiechec, Magnus Borga, Anthony PF Turner and Ashutosh Tiwari, Biosensors and Bioelectronics Centre, Linköping University, Sweden