Related Experiment Video
Updated: May 6, 2026
Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation
Published on: December 15, 2010
Enhanced tumor uptake and penetration of virotherapy using polymer stealthing and focused ultrasound
Robert Carlisle1, James Choi, Miriam Bazan-Peregrino
1Affiliations of authors: Institute of Biomedical Engineering, Department of Engineering Science(RC, JC, C-CC) and Department of Oncology (RL, LWS), University of Oxford, Oxford, UK; Institut d'Investigacio Biomedica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain (MB-P); Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic (VS, LK, KU).
Background:
Oncolytic viruses are among the most powerful and selective cancer therapeutics under development and are showing robust activity in clinical trials, particularly when administered directly into tumor nodules. However, their intravenous administration to treat metastatic disease has been stymied by unfavorable pharmacokinetics and inefficient accumulation in and penetration through tumors.
Methods:
Adenovirus (Ad) was "stealthed" with a new N-(2-hydroxypropyl)methacrylamide polymer, and circulation kinetics were characterized in Balb/C SCID mice (n = 8 per group) bearing human ZR-75-1 xenograft tumors. Then, to noninvasively increase extravasation of the circulating polymer-coated Ad into the tumor, it was coinjected with gas microbubbles and the tumor was exposed to 0.5 MHz focused ultrasound at peak rarefactional pressure of 1.2 MPa. These ultrasound exposure conditions were designed to trigger inertial cavitation, an acoustic phenomenon that produces shock waves and can be remotely monitored in real-time. Groups were compared with Student t test or one-way analysis of variance with Tukey correction where groups were greater than two. All statistical tests were two-sided.
Results:
Polymer-coating of Ad reduced hepatic sequestration, infection (>8000-fold; P < .001), and toxicity and improved circulation half-life (>50-fold; P = .001). Combination of polymer-coated Ad, gas bubbles, and focused ultrasound enhanced tumor infection >30-fold; (4 × 10(6) photons/sec/cm(2); standard deviation = 3 × 10(6) with ultrasound vs 1.3 × 10(5); standard deviation = 1 × 10(5) without ultrasound; P = .03) and penetration, enabling kill of cells more than 100 microns from the nearest blood vessel. This led to substantial and statistically significant retardation of tumor growth and increased survival.
Conclusions:
Combining drug stealthing and ultrasound-induced cavitation may ultimately enhance the efficacy of a range of powerful therapeutics, thereby improving the treatment of metastatic cancer.
Insights
Polymer-coating improved adenovirus (Ad) delivery for cancer treatment. Combining stealth Ad with ultrasound and microbubbles enhanced tumor infection and survival in mice.
Area of Science:
- Oncolytic virotherapy
- Nanomedicine
- Biotechnology
Background:
- Oncolytic viruses show promise for cancer therapy, especially with direct tumor injection.
- Intravenous delivery for metastatic disease is limited by poor pharmacokinetics and tumor penetration.
Purpose of the Study:
- To improve intravenous delivery and tumor penetration of oncolytic viruses.
- To enhance the efficacy of adenovirus (Ad) for treating metastatic cancer.
Main Methods:
- Adenovirus was coated with a polymer (N-(2-hydroxypropyl)methacrylamide) to create a
- stealthed
- Ad.
- Mice bearing human xenograft tumors received polymer-coated Ad, gas microbubbles, and focused ultrasound.
- Ultrasound-induced inertial cavitation was used to enhance drug extravasation and tumor penetration.
Main Results:
- Polymer-coating significantly reduced liver sequestration and toxicity, and increased circulation half-life (>50-fold).
- The combination therapy enhanced tumor infection (>30-fold) and enabled deeper tumor cell kill (>100 microns from blood vessels).
- This approach led to significant tumor growth retardation and increased survival.
Conclusions:
- Combining polymer-based drug
- stealthing
- with ultrasound-induced cavitation can improve therapeutic delivery.
- This strategy holds potential for enhancing the efficacy of oncolytic viruses and treating metastatic cancers.
