Hyperthermia-Mediated Local Drug Delivery by a Bubble-Generating Liposomal System for Tumor-Specific Chemotherapy

Abstract

As is widely suspected, lysolipid dissociation from liposomes contributes to the intravenous instability of ThermoDox (lysolipid liposomes), thereby impeding its antitumor efficacy. This work evaluates the feasibility of a thermoresponsive bubble-generating liposomal system without lysolipids for tumor-specific chemotherapy. The key component in this liposomal formulation is its encapsulated ammonium bicarbonate (ABC), which is used to actively load doxorubicin (DOX) into liposomes and trigger a drug release when heated locally. Incubating ABC liposomes with whole blood results in a significantly smaller decrease in the retention of encapsulated DOX than that by lysolipid liposomes, indicating superior plasma stability. Biodistribution analysis results indicate that the ABC formulation circulates longer than its lysolipid counterpart. Following the injection of ABC liposome suspension into mice with tumors heated locally, decomposition of the ABC encapsulated in liposomes facilitates the immediate thermal activation of CO2 bubble generation, subsequently increasing the intratumoral DOX accumulation. Consequently, the antitumor efficacy of the ABC liposomes is superior to that of their lysolipid counterparts. Results of this study demonstrate that this thermoresponsive bubble-generating liposomal system is a highly promising carrier for tumor-specific chemotherapy, especially for local drug delivery mediated at hyperthermic temperatures.

Self-assembling bubble carriers for oral protein delivery

“…2b). When DTPA dianhydride is exposed to water, an acidic environment is produced [17], in which SBC decomposes to form CO 2 bubbles that are hyperechogenic and could act as a contrast enhancer for ultrasound imaging [18]. The resulting gas pressure forced the capsule to open and quickly released its loaded contents.…”

Enhancement of Hyperthermia on Anti-tumor Drug Sensitivity

“…Thermo-responsive bubble-generating liposomes are being investigated for tumor-specific chemotherapy [11,12]. The key component in this liposomal formulation is its encapsulated ammonium bicarbonate (ABC) which is used to actively load DOX into liposomes and trigger drug release when heated locally.…”

High-intensity focused ultrasound-triggered nanoscale bubble-generating liposomes for efficient and safe tumor ablation under photoacoustic imaging monitoring

“…Importantly, the liposomes were stable enough to cluster in the tumor interstitial space and decomposed to generate CO 2 bubbles under the local heat increase (42°C). 9 The use of liposomes to promote HIFU ablation has the potential to significantly reduce the danger of embolism. Several studies have examined the interaction between HIFU and liposomes, but they mainly focused on HIFU-triggering antitumor drug release from temperature-sensitive liposomes to enhance treatment effects.…”

“…9,27 As depicted in Figure 6, we anticipated that Lip-ABC would safely synergize HIFU ablation. We therefore established animal tumor models ( Figure 7A) and carried out in vivo experiments.…”