Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival

Bioconjug Chem. 2018 Apr 18;29(4):914-927. doi: 10.1021/acs.bioconjchem.7b00816. Epub 2018 Mar 1.


Drug resistance and relapse is common in cancer treatments with chemotherapeutics, and while drug combinations with naturally occurring, differentiation-inducing retinoic acid (RA) provide remission-free cures for one type of liquid tumor, solid tumors present major problems for delivery. Here, inspired by filoviruses that can be microns in length, flexible filomicelles that self-assemble from an amphiphilic block copolymer (PEG-PCL) are shown to effectively deliver RA and paclitaxel (TAX) to several solid tumor models, particularly in the liver. These hydrophobic compounds synergistically load into the cores of the elongated micelles, and the coloaded micelles prove most effective at causing cell death, ploidy, and durable regression of tumors compared to free drugs or to separately loaded drugs. RA-TAX filomicelles also reduce mortality of human lung or liver derived cancers engrafted at liver, intraperitoneal, and subcutaneous sites in immunodeficient mice. In vitro studies show that the dual drug micelles effectively suppress proliferation while upregulating a generic differentiation marker. The results highlight the potency of dual-loaded filomicelles in killing cancer cells or else driving their differentiation away from growth.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Micelles
  • Paclitaxel / administration & dosage*
  • Paclitaxel / therapeutic use
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Tretinoin / administration & dosage*
  • Tretinoin / therapeutic use


  • Antineoplastic Agents
  • Drug Carriers
  • Micelles
  • Polyesters
  • polycaprolactone
  • Polyethylene Glycols
  • Tretinoin
  • Paclitaxel