Smart Cancer Nanotheranostics

QD Solar Chip 2(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.

        drug release mechanism via functional outcome of pH response 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.

     MRI visual order-disorder nanostructure for cancer nanomedicine 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

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Why the Shape of Nanoparticles Matters

QDOTS imagesCAKXSY1K 8(Nanowerk News) Conventional treatments for diseases  such as cancer can carry harmful side effects—and the primary reason is that  such treatments are not targeted specifically to the cells of the body where  they’re needed. What if drugs for cancer, cardiovascular disease, and other  diseases can be targeted specifically and only to cells that need the medicine,  and leave normal tissues untouched?  
A new study involving Sanford-Burnham’s Erkki Ruoslahti, M.D.,  Ph.D., contributing to work by Samir Mitragotri, Ph.D., at the University of  California, Santa Barbara, found that the shape of nanoparticles can enhance  drug targeting. The study, published in Proceedings of the National Academy  of Sciences (“Using shape effects to target antibody-coated  nanoparticles to lung and brain endothelium”), found that rod-shaped  nanoparticles—or nanorods—as opposed to spherical nanoparticles, appear to  adhere more effectively to the surface of endothelial cells that line the inside  of blood vessels.
“While nanoparticle shape has been shown to impact cellular  uptake, the latest study shows that specific tissues can be targeted by  controlling the shape of nanoparticles. Keeping the material, volume, and the  targeting antibody the same, a simple change in the shape of the nanoparticle  enhances its ability to target specific tissues,” said Mitragotri.
“The elongated particles are more effective,” added Ruoslahti.  “Presumably the reason is that if you have a spherical particle and it has  binding sites on it, the curvature of the sphere allows only so many of those  binding sites to interact with membrane receptors on the surface of a cell.”
In contrast, the elongated nanorods have a larger surface area  that is in contact with the surface of the endothelial cells. More of the  antibodies that coat the nanorod can therefore bind receptors on the surface of  endothelial cells, and that leads to more effective cell adhesion and more  effective drug delivery.
Testing targeted nanoparticles
Mitragotri’s lab tested the efficacy of  rod-shaped nanoparticles in synthesized networks of channels called “synthetic  microvascular networks,” or SMNs, that mimic conditions inside blood vessels.  The nanoparticles were also tested in vivo in animal models, and separately in  mathematical models.
The researchers also found that nanorods targeted to lung tissue  in mice accumulated at a rate that was two-fold over nanospheres engineered with  the same targeting antibody. Also, enhanced targeting of nanorods was seen in  endothelial cells in the brain, which has historically been a challenging organ  to target with drugs.
Nanoparticles already used in some cancer drugs
Nanoparticles have been studied as vessels to carry drugs  through the body. Once they are engineered with antibodies that bind to specific  receptors on the surface of targeted cells, these nanoparticles also can, in  principle, become highly specific to the disease they are designed to treat.
Ruoslahti, a pioneer in the field of cell adhesion—how cells  bind to their surroundings—has developed small chain molecules called peptides  that can be used to target drugs to tumors and atherosclerotic plaques.
Promising results
“Greater specific attachment exhibited by rod-shaped particles  offers several advantages in the field of drug delivery, particularly in the  delivery of drugs such as chemotherapeutics, which are highly toxic and  necessitate the use of targeted approaches,” the authors wrote in their paper.
The studies demonstrate that nanorods with a high aspect ratio  attach more effectively to targeted cells compared with spherical nanoparticles.  The findings hold promise for the development of novel targeted therapies with  fewer harmful side effects.
Source: Sanford-Burnham Medical Research Institute 

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