Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors

Biomacromolecules. 2014 Nov 10;15(11):4363-75. doi: 10.1021/bm5013822. Epub 2014 Oct 27.


Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Cholesterol / chemistry*
  • Drug Delivery Systems / methods*
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Polymers / administration & dosage
  • Polymers / chemistry*
  • Random Allocation
  • Xenograft Model Antitumor Assays / methods


  • Antineoplastic Agents
  • Polymers
  • Cholesterol