Pune Scientists Develop Nanomedicine That Switches Off Cancer-Survival Genes

In a significant advance for precision cancer therapy, scientists at the Agharkar Research Institute (ARI), Pune, have developed a next-generation nanomedicine capable of selectively silencing genes that help breast cancer cells survive and resist treatment. This opens new possibilities for safer and more effective cancer care.

The study, published recently in Advanced Healthcare Materials, demonstrates how an engineered biodegradable nanoparticle system can target breast cancer cells, deliver gene-silencing molecules directly to tumours, and suppress critical biological pathways that fuel cancer growth.

The findings come at a time when cancer researchers worldwide are seeking alternatives to conventional chemotherapy, which often damages healthy tissues alongside tumour cells and is associated with significant side effects.

Researchers say the newly developed platform represents an important step towards precision oncology, where treatments are designed to act only on diseased cells while sparing normal tissues.

"Modern cancer treatment is increasingly moving beyond simply destroying tumour cells to precisely targeting the molecular mechanisms that drive cancer progression," the scientists noted. "Gene-silencing technologies offer the possibility of switching off the genes that enable tumours to grow, spread and resist therapy."

The research team from ARI's Nanobioscience Group designed a biodegradable nanocarrier based on mesoporous silica nanoparticles, a material known for its ability to carry large therapeutic payloads and release them in a controlled manner. These nanoparticles were further modified using a naturally occurring biopolymer called protamine and an aptamer that specifically recognises MUC1, a receptor found at unusually high levels on the surface of many breast cancer cells.

This targeting mechanism acts much like a molecular navigation system, enabling the nanoparticles to identify and bind selectively to cancer cells. Once attached, the particles are taken up by the tumour cells, ensuring that the therapeutic molecules are delivered precisely where they are needed.

One of the major challenges in gene therapy has been achieving efficient delivery while avoiding unintended effects on healthy tissues. According to the researchers, the MUC1-targeting strategy substantially improves tumour selectivity and reduces the risk of off-target activity.

The most innovative aspect of the study is its dual gene-silencing approach. Instead of targeting a single cancer-related gene, the nanocarrier simultaneously delivers small interfering RNA (siRNA) molecules against two key anti-apoptotic genes — MCL-1 and Survivin.

These genes function as powerful survival mechanisms for cancer cells, helping them evade programmed cell death and resist treatment. By switching off both genes simultaneously, the researchers aimed to weaken the tumour's defence systems and make cancer cells more vulnerable to destruction.

The nanocarrier has also been engineered to respond to the unique biochemical environment inside tumours. Once it enters cancer cells, elevated levels of glutathione — a naturally occurring molecule found in abundance within tumour tissues — trigger the release of the gene-silencing payload. This ensures that the therapeutic molecules become active primarily within cancer cells rather than elsewhere in the body.

Laboratory studies using MCF-7 breast cancer models showed substantial suppression of both target genes, leading to increased cancer-cell death and marked inhibition of tumour growth.

The encouraging results extended beyond cell-culture experiments. In studies involving Severe Combined Immunodeficiency (SCID) mice carrying breast tumours, the nanocarrier accumulated efficiently at tumour sites and demonstrated significant anti-tumour activity.

Equally important, researchers observed minimal signs of systemic toxicity. Histological examinations of major organs revealed no significant damage, suggesting that the treatment may offer a safer profile than many conventional cancer therapies.

Scientists believe the study highlights the growing potential of RNA interference (RNAi)-based therapies, a field that seeks to control disease by selectively turning off harmful genes. Although the approach remains at the preclinical stage, experts say it addresses several longstanding challenges in gene therapy, including targeted delivery, controlled release, and treatment specificity.

The research was carried out by Niladri Haldar, Rajkumar Samanta, Surajit Patra, Devyani Sengar, Sachin Jadhav and Virendra Gajbhiye of the Nanobioscience Group at the Agharkar Research Institute, Pune.

Researchers say the platform's ability to combine tumour targeting, biodegradable design and simultaneous silencing of multiple cancer-promoting genes offers a promising blueprint for future cancer therapeutics.

As cancer treatment increasingly shifts towards personalised and molecularly guided interventions, such precision nanomedicine approaches could eventually provide patients with therapies that are not only more effective but also considerably less toxic than conventional chemotherapy.