Pharmaceutical Research

, Volume 23, Issue 2, pp 367–377

Specific Delivery of Corroles to Cells via Noncovalent Conjugates with Viral Proteins

  • Hasmik Agadjanian
  • Jeremy J. Weaver
  • Atif Mahammed
  • Altan Rentsendorj
  • Sam Bass
  • Jihee Kim
  • Ivan J. Dmochowski
  • Ruth Margalit
  • Harry B. Gray
  • Zeev Gross
  • Lali K. Medina-Kauwe
Research Paper

DOI: 10.1007/s11095-005-9225-1

Cite this article as:
Agadjanian, H., Weaver, J.J., Mahammed, A. et al. Pharm Res (2006) 23: 367. doi:10.1007/s11095-005-9225-1

Purpose

Corroles are amphiphilic macrocycles that can bind and transport metal ions, and thus may be toxic to cells. We predicted that anionic corroles would poorly enter cells due to the negatively charged cell membrane, but could be ideal tumor-targeted drugs if appropriate carriers enabled delivery into tumor cells. In this work, we test the hypothesis that recombinant cell penetrating proteins of the adenovirus (Ad) capsid form noncovalent conjugates with corroles to facilitate target-specific delivery and cell death.

Methods

Corroles mixed with recombinant proteins were tested for conjugate assembly, cell penetration, stability, targeted binding, and cell killing in vitro.

Results

Sulfonated corroles entered cells only with carrier proteins, and formed stable complexes with recombinant Ad capsid proteins. ErbB receptor-targeted conjugates were cytotoxic to ErbB2-positive but not ErbB2-negative breast cancer cells, whereas molar equivalents of free corrole had no effect on these cells.

Conclusions

Sulfonated corroles are cytotoxic to ErbB2-positive breast cancer cells when delivered by a targeted cell penetrating protein. The relatively low dose required to accomplish this compared to untargeted compounds suggests that corroles may lend themselves to targeted therapy. Importantly, the amphiphilicity of corroles enables a unique approach to bioconjugate formation whereby the carrier and drug form a stable complex by noncovalent assembly.

Key Words

capsid corrole metal penton base targeting 

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Hasmik Agadjanian
    • 1
  • Jeremy J. Weaver
    • 2
  • Atif Mahammed
    • 3
  • Altan Rentsendorj
    • 1
  • Sam Bass
    • 1
  • Jihee Kim
    • 4
  • Ivan J. Dmochowski
    • 5
  • Ruth Margalit
    • 5
  • Harry B. Gray
    • 2
  • Zeev Gross
    • 3
  • Lali K. Medina-Kauwe
    • 1
  1. 1.The Gene Therapeutics Research InstituteCedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Department of ChemistryCalifornia Institute of TechnologyPasadenaUSA
  3. 3.Department of ChemistryTechnion — Israel Institute of TechnologyHaifaIsrael
  4. 4.IntraGene SciencesInstitute for Genetic MedicineLos AngelesUSA
  5. 5.Department of ChemistryUniversity of PennsylvaniaPhiladelphiaUSA

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