CD44-Specific A6 Short Peptide Boosts Targetability and Anticancer Efficacy of Polymersomal Epirubicin to Orthotopic Human Multiple Myeloma

Wenxing Gu, Jingnan An, Hao Meng, Na Yu, Yinan Zhong, Fenghua Meng*, Yang Xu*, Jeroen J.L.M. Cornelissen, Zhiyuan Zhong*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Chemotherapy is widely used in the clinic though its benefits are controversial owing to low cancer specificity. Nanovehicles capable of selectively transporting drugs to cancer cells have been energetically pursued to remodel cancer treatment. However, no active targeting nanomedicines have succeeded in clinical translation to date, partly due to either modest targetability or complex fabrication. CD44-specific A6 short peptide (KPSSPPEE) functionalized polymersomal epirubicin (A6-PS-EPI), which boosts targetability and anticancer efficacy toward human multiple myeloma (MM) in vivo, is described. A6-PS-EPI encapsulating 11 wt% EPI is small (≈55 nm), robust, reduction-responsive, and easy to fabricate. Of note, A6 decoration markedly augments the uptake and anticancer activity of PS-EPI in CD44-overexpressing LP-1 MM cells. A6-PS-EPI displays remarkable targeting ability to orthotopic LP-1 MM, causing depleted bone damage and striking survival benefits compared to nontargeted PS-EPI. Overall, A6-PS-EPI, as a simple and intelligent nanotherapeutic, demonstrates high potential for clinical translation.

Original languageEnglish
Article number1904742
JournalAdvanced materials
Volume31
Issue number46
Early online date27 Sep 2019
DOIs
Publication statusPublished - 15 Nov 2019

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Keywords

  • chemotherapy
  • multiple myelomas
  • nanomedicine
  • polymersomes
  • targeted delivery

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