Molecularly targeted therapy can provide cancer patients with treatments targeting cancerous cells and avoid unnecessary damages to non-cancer cells. However, it is a challenge to deliver the drug to just where the cancerous cells are located. When the drug is distributed to our body, the ultimate goal is to not let it go circulated throughout the body, for the sake of efficiency as well as safety. There is another thera-peutic challenge, which is to detect the metastasis as early as possible.

Professor Michael Hsiao has been studying lung cancer growth and metastasis for quite a long time. Due to the challenges encountered, he started to ponder the possibility of utilizing nanomaterials to solve the problems. A journey of cross discipline collaboration has finally made a significant milestone. On the March 2020 Advanced Science, they gave a report illustrating how a luminous nanomaterial was created and proved to have enhanced the power of an existing therapeutic targeted drug dramatically for non-small cell lung cancer (NSCLC) in an animal model.

Lung cancer cases in Taiwan topped as second in Asia. A first-line targeted drug named afatinib (AFT) can effectively inhibit NSCLC type lung cancer growth and migration. Hsiao’s team wanted to increase the power of its functions and also find a better way to monitor early on to spot any possible spread.

By working with Professor Ru-Shi Liu from the Department of Chemistry in National Taiwan University, they came up with a nanomaterial that would shine in the dark and carry the AFT drug. Furthermore, they managed to install a tiny DNA segment (MAGE-A3 aptamer, MAp) in this nanomaterial. The final prod-uct is like a cruise missile installed with autopilot function, it carries the drug all the way directly to the targeted lung cancer cells, and then release the drug to execute the inhibiting task. This nanomaterial also has an extended illuminating effect, therefore, the scientists could trace the movement of the cancer cells clearly over a period of time.

During the treatment of lung cancer, the one thing doctors dread most is to see the cancer cells grow back at other positions aside from the lung. One spread is seen, the survival rate drops dramatically. According to Dr. Ming-Hsien Chan, the first author of this Advanced Science paper, one of the therapeutic obstacles lies in the lack of methods to differentiate the lung cancer cells from the normal lung cancer cells. Not to mention the difficulties of finding a quick solution to spot the tumor cells migrations.

In their study, persistent luminescence nanoparticles (PLN) was chosen due to its nature of persistent il-lumination once triggered by ultraviolet.

Researchers used the nanoscale silicon dioxide as the base material, and add a metal ion that possesses the PLN characteristics. When they made the lab mice with lung cancer inhale the PLN nanomaterial into their lungs, once an ultraviolet was turned on, they could see clearly the tumor site of the mice had glowing spots. For a period of three weeks, they had observed the progression of these glowing spots expanding from the left lobe of the lung position to the right lobe, all the while these mice were as alive as ever. This proved this PLN nanomaterial is an excellent tool to detect metastasis at an early stage.

 

Multifunctional nanomaterial can track lung changes for up to 12 hours in situ. The therapeutic nanocomposites may allow a chance for effective control of lung cancer growth and metastasis.

 

Professor Liu has a specialty in chemical materials, he explains that this nanomaterial not only can glow for a long period of time, but the holes within like swiss cheese is perfect for carrying therapeutic medi-cines, furthermore, it is doable to release the medicines gradually in a time period of 12 hours.

That could solve the problem of the current use of AFT. Since a known drawback of current AFT treat-ment is that it goes all over the body and requires a too larger amount of dosage and may cause other side effects.

In able to deliver AFT right at the target, they need to add the autopilot feature to this material. They ended up adding an autopilot navigator to PLN. A short DNA sequence was selected, this sequence happens to recognize the MAGE-A3 antibody that is found on the early onset of metastasis. So, they plugged the short DNA sequence to PLN and named it PLN@MAp.

Once the autopilot equipped PLN@MAp is loaded with the AFT and then inhaled by the cancerous mice, they saw the exciting result!

By comparison, these mice treated with AFT-PLN@MAp had minimum weight loss vs. plain AFT treated ones, meaning fewer side effects. Within two weeks, the tumor sizes and weights of the prior group had reduced to 1/4 of the others. This result proved the cruise missile tactic worked beautifully!

Autopsies showed exactly what they hoped to achieve. AFT-PLN@Map can effectively send AFT to the spot, with AFT released at the same spot over a period of time, this strategy maximized the use of AFT and prevented the lung cancer cell growth and migration. “This is the first time in Lung cancer research that nanomaterial is combined with antibody and targeted medicine in treatment.”, explained Dr. Chan.

 

 

“Once material is zoomed in to a nano-scale, whole new properties may show. Adopting the technology to biological entities is a brand new territory with challenges.”, said Chan, “Even though we have mimicked the human body with animal models successfully, there are still loads of tasks to conquer, for example, it is a different matter if we want to make the illumination on human bodies. Yet, given the current develop-ment progresses, luminescence assisted diagnosis should be around the corner”.

Profession Hsiao’s team has the ultimate goal to set up a multi-functional nanomaterial platform. The re-sult of this study is encouraging and they will keep on going on this journey of nano-medicine develop-ment.

The research paper can be read online at: https://onlinelibrary.wiley.com/doi/10.1002/advs.201903741