A Liposomal System Capable of Generating CO₂ Bubbles to Induce Transient Cavitation, Lysosomal Rupturing, and Cell Necrosis

Abstract

Bubbling over: After endocytosis and intracellular trafficking to lysosomes, liposomes containing ammonium bicarbonate can be thermally triggered to generate CO2 bubbles (see scheme). These bubbles grow rapidly and collapse violently to induce transient cavitation, a process that can disrupt the lysosomal membrane and release lysosomal proteases, thus leading to cell necrosis.

Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma

“…5C and D). CO 2 bubble generation in liposomes amplified the cavitation effect [15]. This cavitation effect on lysosomes can mechanically disrupt the cell membranes, resulting in increased necrosis [15].…”

“…To increase drug release from liposomes, we encapsulated both ammonium bicarbonate (NH 4 HCO 3 ) and doxorubicin (DOX) into TSL to generate CO 2 bubbles in response to external hyperthermia [14]. NH 4 HCO 3 is widely used as a CO 2 decompose to generate CO 2 bubbles at temperatures above 40°C [15,16]. Thus, we postulated that external hyperthermia-induced gas generation in liposomes could promote drug release by increasing liposomal membrane destabilization ( Fig.…”

“…Therefore, to increase drug release from liposomes, stimuli-responsive strategies have been developed [5]. Among them, CO 2 generating liposomes were developed for drug burst release from liposomes in response to hyperthermia or ultrasound irradiation [14,15]. The CO 2 generating liposomal platform has been applied to the treatment of diverse diseases such as cancer, demonstrating the system's therapeutic efficacy [1,17].…”

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

“…The mechanism for cell death was determined through flow cytometry using annexin V and PI staining [28]. Increasing the SPI concentrations significantly increased the percentage of cells that underwent necrosis (stained with PI) to 99.5% (Fig.…”

pH-Triggered Echogenicity and Contents Release from Liposomes

“…The results from these two experiments were identical, indicating that the temperature increase did not influence the contents released from our pH-sensitive liposomes. 42 However, we note that one cannot rule out the possibility of local hot spots being generated in the liposomes themselves even when they are in the ice bath. Such temperature hotspot can only be created by the mechanical compression of the air cavity entrapped in the liposomes.…”