Researchers from Tehran University of Medical Sciences, in collaboration with scientists from the Royan Institute, University of Science and Culture (Iran), and De Montfort University (UK), have successfully developed a new generation of smart, size- and charge-switchable nanocarriers capable of delivering the chemotherapy drug doxorubicin (DOX) deep into brain tumor tissue.
October 25, 2025
Scientific
These adaptive PAMAM-based nanocarriers can intelligently adjust their size and surface charge in response to the tumor’s microenvironment, enhancing both tissue penetration and cellular uptake while protecting the drug from degradation in acidic extracellular conditions. The innovation represents a major step toward more effective, less toxic cancer therapies with reduced risk of recurrence.
One of the greatest challenges in cancer therapy is ensuring that drugs can penetrate deep into tumor tissue and be efficiently absorbed by malignant cells. Many chemotherapeutic agents, even after entering the tumor, remain trapped in outer layers or become inactivated in the acidic extracellular matrix.
To address this, the research team designed pH-responsive PAMAM megamers (SChPMs) connected through acid-sensitive linkers and coated with polyethylene glycol (PEG). At neutral pH (7.4), the nanoparticles measure around 100 nm with a surface charge of +0.75 mV, allowing them to circulate stably in the bloodstream. In the acidic tumor microenvironment (pH 6.5), however, they shrink to 15 nm and their surface charge increases to +6.7 mV, promoting deeper tumor penetration and enhanced cellular internalization.
These dynamic changes enable the nanocarriers to bypass tumor barriers, protect the drug from inactivation, and reduce cellular drug resistance. In animal studies using mice bearing 4T1 tumors, the nanocarriers showed strong antitumor activity while causing minimal tissue damage, demonstrating their potential for safe and targeted cancer therapy.
By combining experimental design and molecular simulation, the researchers confirmed that the structural adaptability of these nanocarriers boosts endocytosis and facilitates drug delivery into the tumor core, addressing two of the most persistent obstacles in chemotherapy.
The developed PAMAM nanocarriers effectively deliver doxorubicin to the inner regions of tumors, prevent drug deactivation, and minimize harm to healthy tissues. This approach opens new avenues for next-generation cancer treatments that are both highly effective and biocompatible.
The findings, published in the Journal of Controlled Release under the title “Switchable PAMAM Megamers for Deep Tumor Penetration and Enhanced Cell Uptake”, highlight a promising future for intelligent nanomedicine platforms designed to improve drug bioavailability and patient outcomes in oncology.
Comments
56312 
185906 
312970 
0 
Printable