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Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
Published on: February 8, 2017
Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting
Mami Murakami1, Horacio Cabral, Yu Matsumoto
1Department of Bioengineering, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Science Translational Medicine
|January 7, 2011
Summary
Polymeric micelles loaded with a platinum drug accumulate in tumors and release their payload in late endosomes. This targeted delivery enhances antitumor activity, even in drug-resistant cancers.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Nanocarrier-mediated drug targeting enhances chemotherapy efficacy by accumulating drugs in tumors.
- Polymeric micelles are a promising nanocarrier system for cancer therapy.
Purpose of the Study:
- To investigate the subcellular fate of polymeric micelles incorporating (1,2-diaminocyclohexane) platinum(II) (DACHPt/m).
- To assess the kinetic stability and tumor accumulation of DACHPt/m.
- To evaluate the antitumor activity of DACHPt/m compared to free oxaliplatin.
Main Methods:
- Real-time fluorescence-based assessment of DACHPt/m in tumor tissues.
- Kinetic stability analysis of nanocarriers.
- Comparison of antitumor activity in vitro and in vivo.
Main Results:
- DACHPt/m extravasated from blood vessels and dissociated within tumor cells.
- Selective dissociation of DACHPt/m occurred in late endosomes, facilitating nuclear drug delivery.
- DACHPt/m demonstrated enhanced antitumor activity compared to oxaliplatin, including against resistant tumors.
Conclusions:
- Nanocarriers can be engineered to target specific subcellular compartments for improved drug delivery.
- DACHPt/m exhibits superior efficacy by circumventing cellular drug resistance mechanisms.
- Subcellular targeting nanocarriers hold significant potential for clinical cancer therapy.
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