Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 17, Issue -, Pages 2001-2017Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S344940
Keywords
microbubbles; cavitation effect; glioblastoma; focused ultrasound
Funding
- National Key R&D Program of China [2020YFA0908800]
- National Natural Science Fund of China [U1804187, 81971638, 12074269]
- Shenzhen Science and Technology Program [JCYJ20210324105415040, JCYJ20190809105207439]
- Guangdong Natural Science Fund [2020A1515010395]
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A new drug-loaded microbubble complex based on PLGA was developed to target GA to brain tumors through UTMD. The combination of GA/PLGA-CMB with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines and effectively opened the BBB for targeted treatment of glioblastoma in a mouse model.
Background: The blood-brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma. Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD. Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice. Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P<0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P<0.05). Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.
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