Nano Bombs : Brahmastra to Fight Cancer

‘Asuras’ are superpower-seeking beings, who have the ability to rapidly heal from any damage. Asuras are always in constant conflicts with the good beings, ‘Devtas’. They were initially good beings, virtuous and powerful, but their nature changed with time, sharing the character of immortal powerful beings that were obsessed with their hunger for ill-gotten ‘Somraas’ to become immortal. They evolved into anti-Devtas and threatened the peaceful exitance of Devtas. Asuras need to be destroyed.

Just as the mythological world is characterized by good and bad beings, our human body too has good cells and bad cells or rather say Devtas (normal cells) and Asuras (cancer cells). Here, the Devtas, are normal body cells that have mortal lives, with a defined life cycle. Unlike these Devtas, Asuras are cancer cells that continue to grow and divide out of control (immortal) and don't die when they're supposed to. They aim at controlling and destroying the kingdoms (organs) of Devta cells, to form tumors that demolish the smooth functioning of these kingdoms. With growing greed and power, the Asura cells move away from the original tumor kingdom and send their army of Asuras through leaky tunnels (blood vessels) and establish other tumor kingdoms (organs), where they keep growing and forming new Asura (tumor) kingdoms. The spread of a tumor to a new place in the body is called metastasis.

“Now, one might ask…. Why did Devta cells turn into Asura cells?”

It all started ages ago when Devta cells were happily ruling their kingdoms and flourishing with prosperity. This demanded an improved lifestyle with increased dependence on artificial (synthetic) food and drinks - Somraas. A few Devta cells competed for more power intoxicating synthetic - Somraas to achieve immortality leading to the birth of the Asuras – Cancer.

Cancer! Cancer is a word that resonates fear among people, this disease is one of the leading causes of global mortality. Common people are not aware that cancer was part of human civilization since ages, first case being documented in Egyptian period. Then later in the 20th century, the number of cancer incidences increased owing to explosion of population, rapid industrialization, greed for synthetic food and craving for luxury lifestyle. India alone had 13.9 lakh cases of cancer in 2020 and this number is likely to increase to 15.7 lakh by 2025, with estimation of almost 60% succumbing to death. The primary reason for the higher death rate in the Indian population is the absence of an effective, preventive and economical approach for cancer, in spite of continued research to develop new anti-cancer therapies. 

Powerful immortal Asuras, known for their self-healing and fast spreading character were not easy to suppress with the regular weapons (surgery, chemotherapies, radiations) as it damaged both its own Devta cells along with the Asura cells. Hence, the quests for simple, fast, scalable, target-specific and economical weapons (therapies) began. Through serendipity, a new weapon was made with special properties intended to harm only the bad cells. It is called ‘Brahmastra-NanoBombs’.

Our research group has been looking into strategies to overcome these ‘Asura cells’, with my Ph.D. research revolving around designing newer and safer anti-cancer ‘weapons-NanoBombs’ (therapeutic agents). The work focused on developing simple, effective, cancer-specific and economic anticancer weapons Nanobombs (therapeutic agents), comprising of ‘nanoparticles’ synthesized by scalable and green processes. These weapons were made from the highly unexplored Palladium metal that has proven anti-cancer activity. Normally palladium metal is extensively used for chemical reactions due to its unique remarkable stability, as well as good catalytic and mechanical properties. Taking advantage of these properties; palladium metal in nanoform (dimensions invisible to naked eyes) was chosen for deeper experimentation into its potential anti-cancer activity. Generally, pure palladium metal is toxic towards cells, by itself, and hence requires modification to impart bio-friendly properties. This biofriendly nature was imparted by combining palladium with trimethyl chitosan (TMC), a type of natural “chitosan” polymer. Chitosan is extracted from the marine waste and hence is easily and economically available. The aim of using modified chitosan has huge benefits as it enhances its attraction towards cell membrane having complimentary characteristics. The TMC was developed in our lab by a new green technology. The green process avoided the use of conventional harsh and toxic chemicals, but used bio-catalysts and environmentally friendly solvents or deep eutectic solvents (ionic liquids), instead. These nanoparticles of TMC combined with palladium can be generated in bulk with reproducible shapes and sizes, by producing them in microfluidic devices, or miniaturized “factory-on-a-chip”. These devices are powerful instruments that are compact and cost-effective. They consist of small channels, typical of dimensions in scale of micrometers, through which continuous streams of two phases (oil and water) flow. The formation of nanoparticles takes place in the aqueous phase. The device is integrated with a special 3D printed collector for continuous separation of the aqueous phase (nanoparticles) from the oil, based on simple gravity. The separation of nanoparticles solution by this method demolishes the need for any energy extensive purification step. The microfluidic system yielded highly uniform nanoparticles of size 30-40 nm, which had a special thermal property to selectively kill cancer cells.

It is said a chain is only as strong as its weakest link, Asuras too did have a weakness. The rarely manipulated weakness was that Asuras were vulnerable to higher temperatures, as they lacked the system to tolerate temperature above 40°C. Hence, exploiting this weakness, the NanoBombs are efficiently and specifically (targeted therapy) planted in the Asura’s kingdom (tumor). The Asuras are incapable of predicting the true magical power (anti-cancer property) of NanoBombs. It was when their kingdom was illuminated with light (Near-Infrared laser), Asuras could sense a sudden rise in temperature. Before all the Asuras could understand this sudden event, there was an instant massacre of all Asuras, within minutes. The Devtas emerged victoriously. This event is called is photothermal-therapy (PTT).

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PTT is a localized heat stress treatment, initiated by photothermal conversion by palladium nanoparticles, allowing the selective killing of the tumor cells. Palladium metal nanoparticles have a higher ability to convert light energy to heat and possess improved stability compared to contemporary metal nanoparticles at the near-infrared (NIR) regions of light. In these regions, human tissues have the maximum capability to transmit light without harming cells. Hence, the developed palladium nanoparticles are suitable candidates for PTT due to their unique optical properties. This photothermal ability of nanoparticles was successfully demonstrated in our laboratory setting using a culture of breast cancer cells. The nanoparticles were able to increase the temperature to over 50°C, effectively killing susceptible cancer cells. The PTT technology demonstrated through this work has a promising future and can be actively pursued over conventional treatments due to its non-invasiveness, strong specificity, and high tumor-killing efficiency.

Concurrently, India is witnessing a crisis building up over a decade to treat cancer. And in the present post-covid scenario, India is emerging as a global hub for healthcare innovations due to increased R and D investments. Thus, these factors can propel the growth of markets for microfluidic technologies and nanomedicines to provide simple, effective and scalable anti-cancer therapies that use green technologies to mass-produce therapeutics to obviate the global, ever increasing health and economic burden.