Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells

Rahul Nahire, Manas K. Haldar, Shirshendu Paul, Avinash H. Ambre, Varsha Meghnani, Buddhadev Layek, Kalpana S. Katti, Kara N. Gange, Jagdish Singh, Kausik Sarkar, Sanku Mallik

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they also demonstrate a slow release for the encapsulated contents, limiting their efficacy as a drug-delivery tool. As a solution, we prepared and characterized echogenic polymersomes, which are programmed to release the encapsulated drugs rapidly when incubated with cytosolic concentrations of glutathione. These vesicles encapsulated air bubbles inside and efficiently reflected diagnostic-frequency ultrasound. Folate-targeted polymersomes showed an enhanced uptake by breast and pancreatic-cancer cells in a monolayer as well as in three-dimensional spheroid cultures. Polymersomes encapsulated with the anticancer drugs gemcitabine and doxorubicin showed significant cytotoxicity to these cells. With further improvements, these vesicles hold the promise to serve as multifunctional nanocarriers, offering a triggered release as well as diagnostic ultrasound imaging.

Original languageEnglish (US)
Pages (from-to)6482-6497
Number of pages16
JournalBiomaterials
Volume35
Issue number24
DOIs
StatePublished - Aug 2014

Bibliographical note

Funding Information:
This research was supported by NIH grant 1R01 CA 113746 as well as NSF grants DMR 1005011 and DMR 1306154 to SM; DMR 1005283 , and NIH grant P20RR016472 to KS.

Keywords

  • Drug delivery
  • Gemcitabine
  • Liposome
  • Pancreatic cancer
  • Polymersome

Fingerprint Dive into the research topics of 'Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells'. Together they form a unique fingerprint.

Cite this