Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system for tumor-specific chemotherapy

Ko Jie Chen, Er Yuan Chaung, Shiaw Pyng Wey, Kun Ju Lin, Felice Cheng, Chia Chen Lin, Hao Li Liu, Hsiang Wen Tseng, Chih Peng Liu, Ming Cheng Wei, Chun Min Liu, Hsing Wen Sung

Research output: Contribution to journalArticlepeer-review

153 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5105-5115
Number of pages11
JournalACS Nano
Issue number5
Publication statusPublished - May 27 2014
Externally publishedYes


  • biodistribution
  • doxorubicin
  • local drug delivery
  • thermoresponsive liposome
  • triggered release

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy


Dive into the research topics of 'Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system for tumor-specific chemotherapy'. Together they form a unique fingerprint.

Cite this