Cancer is a global threat to mankind. Over the years, significant understanding of the causes, behaviour, and drugs required to treat various cancers has accumulated. However, therapeutic procedures for cancer remain a major concern for scientists.
Depending on the type or location, cancers can be treated through medicines or surgical resection/amputation. However, the recurrence rate of tumours is high after surgery, and chemotherapy remains the primary treatment against tumour recurrence. India accounts for about seven per cent of the global cancer burden, with the highest cancer incidence reported from the North-Eastern Region (NER).
The National Centre for Disease Informatics & Research (NCDIR), Bengaluru, in its 2021 report titled Profile Cancer and Related Health Indicators in the Northeast Region of India, projects that the number of new cancer cases in the region is likely to increase to 57,131 by 2025, compared to the estimated 50,317 in 2020. Across the region, oesophageal cancer is most prevalent among males (13.6%), followed by lung cancer (10.9%) and stomach cancer (8.7%). Among females, breast cancer is the leading type (14.5%), followed by cervical cancer (12.2%) and gall bladder cancer (7.1%).
Oral or intravenous drug intake is often ineffective unless the formulation includes a targeted delivery vehicle. Even with the incorporation of targeting groups, intravenous delivery systems face several drawbacks, such as drug loss leading to excessive dosage requirements and interaction with healthy cells, which cannot be entirely prevented due to the systemic flow of blood. Local administration of drugs, or a localised drug delivery system (LDDS), is a more attractive treatment method, and several experimental systems have been explored.
Researchers from the Indian Institute of Technology Guwahati and Bose Institute Kolkata have now developed an advanced injectable hydrogel for localised cancer treatment. This innovative hydrogel-based therapy delivers anti-cancer drugs directly to tumour sites, significantly reducing the side effects typically associated with conventional cancer treatments. The findings have been published in Materials Horizons, a journal of the Royal Society of Chemistry. The paper is co-authored by Prof. Debapratim Das, along with research scholars Tanushree Das and Ritvika Kushwaha from IIT Guwahati, and collaborators Dr Kuldip Jana, Satyajit Halder, and Arnup Kumar Misra from Bose Institute Kolkata.
Prof. Das, from the Department of Chemistry, IIT Guwahati, explained, “So far, we have studied this for breast cancer, but in principle, it should work for any type of tumour except leukaemia or cancers in areas with regular fluid flow, such as the respiratory tract, mouth, or digestive tract. We are now working on other types of cancer like liver and kidney. It is a general treatment policy and can certainly help the people of the North East.”
He added, “In men from the North East, oesophageal cancer is the most prevalent, as far as I know. I am not sure if this treatment will be helpful for that. We are applying for clearance for a clinical trial, and if approved, it may take a few more years to be available to the public, provided the results are positive. At this point, we are looking for a suitable industrial partner.”
The hydrogel, formulated using PyKC (peptide-based hydrogel peptides), offers unique properties ideal for localised drug delivery. Its injectable nature ensures ease of application, while its stability in biological fluids prevents premature dissolution. Most importantly, the hydrogel responds to elevated levels of glutathione (GSH), typically found in tumour microenvironments. This specificity allows controlled, sustained release of the anti-cancer drug doxorubicin (DOX), directly targeting cancerous tissues while sparing healthy cells.
In laboratory settings, a single dose of DOX-loaded hydrogel resulted in significant tumour regression, reducing tumour size by approximately 75% within 18 days in a murine breast cancer model. The hydrogel remained intact at the tumour site, ensuring prolonged drug availability and effectiveness. Elevated GSH levels in cancer cells trigger the hydrogel’s dissolution, releasing DOX in a controlled manner, minimising off-target effects and reducing cytotoxic impact on healthy tissues.
In vitro experiments highlighted its potential. Compared to free DOX, the DOX-loaded hydrogel demonstrated enhanced cytotoxicity against breast cancer cell lines, inducing significant cell cycle arrest and apoptosis. This dual mechanism not only halts cancer cell proliferation but also promotes programmed cell death, aided by increased reactive oxygen species levels and disrupted mitochondrial function.
The hydrogel’s composition ensures biocompatibility and minimal toxicity. Unlike polymeric delivery systems requiring chemical modifications, the peptide-based hydrogel is derived from natural amino acids, making it easily degradable and safe for clinical applications. In vivo studies on mice showed significant tumour size reduction without adverse effects such as weight loss or organ toxicity. Histological analyses confirmed minimal damage to vital organs, highlighting the hydrogel’s safety profile.
Prof. Das remarked, “This work exemplifies how scientific innovation can directly address the pressing needs of cancer treatment. The hydrogel’s unique properties allow it to work in harmony with the biological environment, offering precision where it is needed most. We are excited by its potential to transform our understanding of localised drug delivery.”
The success of the DOX-loaded PyKC-hydrogel represents a significant leap forward in cancer therapy. Its localised delivery system addresses the limitations of traditional chemotherapy while aligning with personalised medicine principles. By tailoring treatment to the tumour microenvironment, this approach maximises therapeutic efficacy while minimising collateral damage. Future research will likely focus on optimising this hydrogel for human applications, exploring its potential in other cancer types, and combining it with complementary therapies. With its multifaceted advantages, the PyKC-hydrogel is poised to become a cornerstone of next-generation cancer treatments, offering hope for safer, more effective solutions.
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