A Gambogic Acid-Loaded Delivery System Mediated by Ultrasound-Targeted Microbubble Destruction: A Promising Therapy Method for Malignant Cerebral Glioma

Abstract

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.

Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers

“…The host-guest interaction of avidin-biotin was used to modify the targeting ligand on the MBs’ surface ( Scheme 2 c) [ 62 , 65 ]. Because the surface area or shell volume of the MBs is restricted, modification of the liposomes on the MBs’ surface provides a larger space for accommodating medicinal materials ( Scheme 2 d) [ 28 , 66 , 67 , 68 , 69 , 70 ].…”

Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

“…Other authors combined charged MB with the negatively charged Gambogic Acid (GA) (an active component of a traditional Chinese medicine effective as antiproliferative and tumor infiltration agent) loaded polymeric nanoparticle (GA/PLGA) to form a GA/PLGA-charged MB complex (Dong et al, 2022). Similarly, FUS application benefits the distribution and long-term accumulation of 89 Zr labeled/cetuximab, an anti EGFR antibody in a preclinical mouse model (Sacks et al, 2018).…”