Photo-crosslinked hyaluronic acid nanoparticles with improved stability for invivo tumor-targeted drug delivery

Hong Yeol Yoon, Heebeom Koo, Ki Young Choi, Ick Chan Kwon, Kuiwon Choi, Jae Hyung Park, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


One of the major hurdles of the nanoparticles as drug carriers is the unintended burst release of loaded drugs during blood circulation. To surmount this issue, we developed photo-crosslinked hyaluronic acid nanoparticles (c-HANPs) with improved stability for tumor-targeted drug delivery. They were readily prepared via UV-triggered chemical crosslinking with the acrylate groups in the polymer backbone. The size of c-HANPs was not much different from that of uncrosslinked HANPs. However, c-HANPs exhibited significantly high stability in a physiological buffer and released the loaded drug, paclitaxel (PTX), in a sustained manner. It is noteworthy that the drug release rate from c-HANPs remarkably increased in the presence of hyaluronidase, an enzyme abundant at the intracellular compartments of the tumor cells. It was found from invitro cellular uptake tests that c-HANPs were rapidly taken up by the tumor cells via the receptor (CD44)-mediated endocytosis, which was not inhibited by photo-crosslinking. In non-invasive animal imaging results, they showed higher tumor-targeting ability than uncrosslinked HANPs because high stability of c-HANPs enabled their long circulation in the body. Owing to the sustained release of the drug and enhanced tumor-targeting ability, c-HANPs showed higher therapeutic efficacy compared to free PTX and uncrosslinked HANPs. These data implied the promising potential of c-HANP as tumor-targeting drug carriers and demonstrated the remarkable effect of the improved stability upon the biodistribution and therapeutic efficacy of drug-loaded nanoparticles.

Original languageEnglish
Pages (from-to)5273-5280
Number of pages8
Issue number21
StatePublished - Jul 2013

Bibliographical note

Funding Information:
This work was financially supported by the Global Research Laboratory (GRL) Project and the Basic Science Research Program (20100027955 & 2012012827) of MEST , and Company-Researcher co-work program of Small & Medium Business Administration (SD122946).


  • Crosslinking
  • Drug delivery
  • Hyaluronic acid
  • Polymeric nanoparticle
  • Stability


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