Nanotechnology for targeted drug delivery

As per the 2020 report from the World Health Organisation’s International Agency for Research on Cancer, global cancer incidence is increasing with India ranking third in reported cases after China and the USA. In 2020, 8.5 lakh Indians succumbed to cancer, contributing to the ten million global deaths from the disease. Projections indicate a 12.8 per cent rise in Indian cancer cases by 2025. Moreover, global new cancer cases are anticipated to surge by approximately 47 per cent by 2040.

Cancer originates from uncontrolled cell growth, resulting in disrupted cellular activity and regulated cell death, facilitating distant spread. Changes in the tumour microenvironment redirect nutrients to support its growth. This gives rise to a diverse cell population with varying responses to treatment.

Since 1949, when Nitrogen Mustard was introduced as a chemotherapy agent, cancer care has evolved significantly. In addition to chemotherapy, surgical interventions and radiotherapy have emerged as additional modalities in cancer treatment.

Chemotherapy drugs encounter limitations including variable penetration across physiological barriers, drug resistance, and toxicity to normal cells. Additionally, accompanying solvents can worsen toxicity. To tackle challenges such as poor solubility, adverse effects on normal cells, limited cancer cell targeting, and rapid drug clearance, researchers are actively developing various nano-drug carriers (NDDS).

Nanotechnology originated from the Nobel Laureate Richard Feynman’s Caltech lecture, “There is Plenty of Room at the Bottom,” envisioning precise atomic arrangement. Nanoscience explores material traits within the 1 to 100-nanometer range, while nanotechnology applies this knowledge to manipulate objects. In 1999, Robert A Freitas introduced “nanomedicine,” marking the fusion of nanotechnology with medical applications.

Nanocarriers facilitate precise drug delivery to cancer sites with controlled release. Nano cancer therapy began with liposomes, small spherical structures enveloped in fat, containing Doxorubicin (DOXIL), a chemotherapy drug targeting cancer cells by gene damage and cell reproduction disruption. FDA (USA) approved DOXIL in 1995. Since 2000, various other drug carriers emerged. Harvard researchers pioneered a “nano-robot” for targeted anticancer drug delivery.

Targeted nano-therapy surpasses conventional chemotherapy with reduced toxicity, improved permeability to target sites, and enhanced nanoparticle accumulation in tumours. Yet, the immune system may identify and eliminate nanoparticles as foreign. To address this, nanoparticle surfaces are modified to evade detection. Advancements in nanoparticle engineering include smarter particles that degrade at the tumour site, enhancing tissue penetration. This strategy has successfully delivered chemotherapy drugs like Cisplatin.

Heat energy is gaining traction as a method to target cancer cells, leveraging cancer cell’s restricted blood supply. Photothermal therapy (PTT) employs light-absorbing nanoparticles to convert light into heat, elevating temperatures at tumour sites. Hyperthermia therapy (elevating temperatures) offers an alternative to chemotherapy. Cancer cells are more vulnerable to heat than normal cells, and temperatures above 42°C can trigger cancer cell death while sparing normal cells.

Copper Sulfide nanoparticles have emerged as a notable candidate for Photothermal therapy.

Gold nanoparticles, on the other hand, exhibit the ability to deliver both small and large drug molecules to the tumour site, demonstrating anti-cancer effects. Nevertheless, their substantial size poses a limitation to tissue penetration.

Professor Ashok Raichur and his team from the Department of Materials Engineering at the Indian Institute of Science (IISC), Bengaluru, have pioneered the development of an ultra-small Copper Sulfide-Silver nanohybrid. Their laboratory experiments have demonstrated promising anti-cancer effects, particularly in lung cancer models where it was evaluated. 

Elaborating on this breakthrough, Professor Raichur explains that these nanohybrids possess the unique ability to generate sound waves upon light absorption, offering potential applications in tumour imaging as well.

Professor Neetu Singh, from the Centre for Biomedical Engineering at the Indian Institute of Technology, New Delhi, has been investigating the utilisation of red blood cells as a more biologically compatible option for nanocarriers. 

Through a breakdown process, the contents of red blood cells are removed, leaving behind ghost cells with lipid coverings. These ghost cells undergo pressurised processing to create nanoparticles.

These nanoparticles exhibit prolonged circulation, potentially opening new avenues for drug delivery. Professor Neetu is optimistic about the future possibilities of personalised medicine that this approach can facilitate.

Prof R Nagarajan and Dr M Joyce Nirmala from the Department of Chemical Engineering at the Indian Institute of Technology Madras have developed two patented Indian spice-based cancer nanomedicines that have potent anticancer activity against lung, breast, colon, cervical, and oral cancer cell lines. The drug safety limits are validated through animal studies and the efficacy studies in nude mice are in progress. The developed formulations are non-invasive, safe, and cost-effective. Further, measures are taken to carry out clinical trials.

The field of nano-drug delivery offers promising drug delivery options. However, a detailed study of nanocarriers’ effectiveness and toxicity in suitable animal models must be performed to ensure a higher rate of clinical translation.

What is nanotherapy?
Nanoparticles can be used in targeted drug delivery to improve the bioavailability, biodistribution, and accumulation of therapeutics, preferentially in the targeted diseased area, acting as stability enhancers.

What are the benefits of nanotherapy?
By enabling rapid and sensitive detection of cancer-related molecules, nanotechnology empowers scientists to detect molecular changes, even in a small percentage of cells. Moreover, nanotechnology has the potential to generate entirely novel and effective therapeutic agents.
Targeted nano-therapy surpasses conventional chemotherapy with reduced toxicity, improved permeability to target sites, and enhanced nanoparticle accumulation in tumours.

Chemotherapy vs nanotechnology
Chemotherapy drugs encounter limitations including variable penetration across physiological barriers, drug resistance, and toxicity to normal cells. Additionally, accompanying solvents can worsen toxicity. To tackle challenges such as poor solubility, adverse effects on normal cells, limited cancer cell targeting, and rapid drug clearance, researchers are actively developing various nano-drug carriers (NDDS).

Nanocarriers facilitate precise drug delivery to cancer sites with controlled release. Nano cancer therapy began with liposomes, small spherical structures enveloped in fat, containing Doxorubicin (DOXIL), a chemotherapy drug targeting cancer cells by gene damage and cell reproduction disruption. FDA (USA) approved DOXIL in 1995. Since 2000, various other drug carriers emerged. Harvard researchers pioneered a “nano-robot” for targeted anticancer drug delivery.

(The author is a consultant haemato-oncologist with a special interest in stem cell transplantation at Royal Wolverhampton NHS Trust, UK.
He can be reached at [e-mail])