Tumor vascular permeabilization using localized mild hyperthermia to improve macromolecule transport

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Abnormal tumor vasculature hinders chemotherapeutic delivery, limiting treatment efficacy.
• Nanoparticle-based strategies are needed to overcome drug delivery challenges in tumors.

Purpose of the Study:

• To develop and evaluate a nanoparticle-based localized mild hyperthermia (MHT) technique.
• To enhance macromolecule transport into tumor interstitium by transiently altering vascular properties.

Main Methods:

• Stealth gold nanorods (GNRs) were administered to localize in tumors.
• Tumors were irradiated with low-photon laser flux to induce MHT.
• Mathematical modeling and intravital microscopy assessed changes in vascular transport properties.

Main Results:

• MHT treatment increased vascular permeability, enhancing transport of macromolecules up to 54 nm.
• Macromolecular exchange rate (R) increased by 200%, and maximum dye enhancement (Ymax) by 30% for 23-nm dextran.
• Enhanced transport was observed for up to 24 hours post-treatment and was reversible within 36 hours.

Conclusions:

• Localized MHT using GNRs creates a transient window for augmented macromolecule transport into tumors.
• This approach shows potential for improving therapeutic efficacy by enhancing drug delivery.
• The method offers a promising strategy for treating drug-resistant malignancies.