Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors.

Abstract

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.

• Authors: Chaopei Zhou, Xiangyang Xie, Hong Yang, Shasha Zhang, Yinke Li, Changchun Kuang, Shiyao Fu, Lin Cui, Meng Liang, Chunhong Gao, Yang Yang, Chunsheng Gao, Chunrong Yang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 16 Issue 7 Pg. 2956-2965 (07 01 2019) ISSN: 1543-8392 [Electronic] United States
• PMID: 31084010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Chlorophyllides
• Drug Carriers
• Lipid Bilayers
• Liposomes
• Oligopeptides
• Porphyrins
• Radiation-Sensitizing Agents
• asparagine-glycine-arginine
• phytochlorin
• Doxorubicin
• CD13 Antigens

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage)
• CD13 Antigens (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chlorophyllides
• Doxorubicin (administration & dosage)
• Drug Carriers
• Drug Delivery Systems (methods)
• Drug Liberation (radiation effects)
• Fibrosarcoma (drug therapy, metabolism, pathology)
• Humans
• Lipid Bilayers (radiation effects)
• Liposomes (chemistry)
• Mice
• Mice, Nude
• Oligopeptides (chemistry, metabolism)
• Porphyrins (chemistry)
• Radiation-Sensitizing Agents (chemistry)
• Tumor Burden (drug effects)
• Ultrasonic Waves
• Xenograft Model Antitumor Assays