Navigation Links
Normalizing tumor blood vessels improves delivery of only the smallest nanomedicines
Date:4/9/2012

Combining two strategies designed to improve the results of cancer treatment antiangiogenesis drugs and nanomedicines may only be successful if the smallest nanomedicines are used. A new study from Massachusetts General Hospital (MGH) researchers, appearing in Nature Nanotechnology, finds that normalizing blood vessels within tumors, which improves the delivery of standard chemotherapy drugs, can block the delivery of larger nanotherapy molecules.

"We found that vascular normalization only increases the delivery of the smallest nanomedicines to cancer cells," says Vikash P. Chauhan, of the Steele Laboratory of Tumor Biology in the MGH Radiation Oncology Department, lead author of the report. "We also showed that the smallest nanomedicines are inherently better than larger nanomedicines at penetrating tumors, suggesting that smaller nanomedicines may be ideal for cancer therapy."

Tumors need to generate their own blood supply to continue growing, but vessels supplying tumors tend to be disorganized, oversized and leaky. Not only does this prevent the delivery of chemotherapy drugs to cells not close to tumor vessels, but the leakage of plasma out of blood vessels increases pressure within the tumor, further reducing the ability of drugs to penetrate tumors. Treatment with drugs that inhibit angiogenesis the process by which new vessels are generated reduces some of these abnormalities, a process called vascular normalization that has been shown to improve treatment of some cancers with standard chemotherapy drugs.

Nanomedicines are actually designed to exploit tumor vessel abnormality. While the molecules of standard chemotherapy drugs are about one nanometer a billionth of a meter nanomedicine molecules are from 10 to 100 times larger, too large to penetrate the pores of blood vessels in normal tissues but small enough to pass through the oversized pores of tumor vessels. Since the size of nanomedicines should keep them out of normal tissues, they are prescribed to reduce the negative side effects of chemotherapy.

The current study was designed to investigate whether the use of antiangiogenesis drugs to normalize tumor vasculature would improve or impede delivery of nanomedicines to tumor cells. In studies using a mouse model of breast cancer, the investigators first confirmed that treatment with DC101, an antibody to a molecule essential to blood vessel growth, temporarily decreased the diameter of enlarged tumor blood vessels. They then showed that this vascular normalization improved the penetration into tumors of 12-nanometer particles but not of 60- or 125-nanometer molecules.

A mathematical model prepared by the MGH team predicted that, while the abnormally large pores in the walls of tumor blood vessels lead to increased pressure within the tumor that impedes the entry of drugs, reducing pore size by antiangiogenesis treatment would relieve intratumor pressure, allowing the entry of those molecules that fit through the smaller pores. To test this prediction, they treated mice with implanted breast tumors either with DC101 and Doxil, a 100-nanometer version of the chemotherapy drug doxorubicin, or with DC101 and Abraxane, a 10-nanometer version of paclitaxel. Although treatment with both chemotherapeutics delayed tumor growth, vascular normalization with DC101 improved the effectiveness only of Abraxane and had no effect on Doxil treatment.

"A variety of anticancer nanomedicines are currently in use or in clinical trials," says Chauhan, who is a graduate student at the Harvard School of Engineering and Applied Sciences (SEAS). "Our findings suggest that combining smaller nanomedicines with antiangiogenic therapies may have a synergistic effect and that smaller nanomedicines should inherently penetrate tumors faster than larger nanomedicines, due to the physical principles that govern drug penetration. While it looks like future development of nanomedicines should focus on making them small around 12 nanometers in size we also need to investigate ways to improve delivery of the larger nanomedicines that are currently in use."

"Antiangiogenic agents are prescribed to a large number of cancer patients in combination with conventional therapeutics," explains Rakesh K. Jain, PhD, director of the Steele Lab and senior and corresponding author of the Nature Nanotechnology report. "Our study provides guidelines on how to combine the antiangiogenic drugs with nanotherapeutics." Jain is Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School.


'/>"/>
Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Novel Method Eyed for Normalizing Blood Sugar
2. Improved Stem Cell Line May Avoid Tumor Risk: Study
3. Oxygen in tumors predicts prostate cancer recurrence
4. 2 targeted therapies act against Ewings sarcoma tumors
5. Freezing Secondary Breast Cancer Tumors Shows Promise
6. Cancer treatment system sculpts radiation beam to match shape of a tumor
7. How cancer cells start new tumor sites
8. Rare medical phenomenon of systemic tumor disappearance following local radiation treatment reported in a patient with metastatic melanoma
9. Study shows advance in using patients own tumor-fighting cells to knock back advanced melanoma
10. A culprit behind brain tumor resistance to therapy
11. Vitamin D shrinks fibroid tumors in rats
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements ... that was developed to enhance the health of felines. The formula is all-natural and ... main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews are ...
(Date:6/25/2016)... , ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on ... Observer , brings up a new, often overlooked aspect of head lice: the parasite’s ability ... fumigation is not a common occurrence, but a necessary one in the event that lice ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary ... Work award to iHire in recognition of their exemplary accomplishments in worksite health promotion. ... Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. Her ... would lash out at his family verbally and physically. , “When something upset him, he ... he would use it. He would throw rocks at my other children and say he ...
(Date:6/24/2016)... ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, ... minimum wage raise to $12 an hour by 2020 and then adjusting it yearly to ... value of the minimum wage, assure the wage floor does not erode again, and make ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Belgium , June 24, 2016 /PRNewswire/ ... announced the appointment of Dr. Edward Futcher ... a Non-Executive Director, effective June 23, 2016.Dr. Futcher ... and Nominations and Governance Committees.  As a non-executive ... provide independent expertise and strategic counsel to VolitionRx ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... - Forecast to 2022" report to their offering. ... for the patients with kidney failure, it replaces the function ... the patient,s blood and thus the treatment helps to keep ... in balance. Increasing number of ESRD patients ...
(Date:6/23/2016)... Ill. , June 23, 2016  In a startling report ... are failing their residents by lacking a comprehensive, proven plan to ... a definitive ranking of how states are tackling the worst ... to only four states – Kentucky , ... Vermont . Of the 28 failing states, three ...
Breaking Medicine Technology: