Transferrin-binding peptide functionalized polymersomes mediate targeted doxorubicin delivery to colorectal cancer in vivo

Yaohua Wei^a,b, Xiaolei Gu^a, Yinping Sun^a, Fenghua Meng^{a, *}（孟凤华）, Gert Storm^b, Zhiyuan Zhong^{a, *}（钟志远）

^aBiomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, PR China

^bDepartment of Biomaterials Science and Technology, MIRA Institute for Biological Technology and Technical Medicine, University of Twente, PO Box 217, 7500AE Enschede, the Netherlands

Journal of Controlled Release 319(2020) 407--415

Transferrin receptor (TfR) is a promising target validated in the clinical trials for managing various malignancies. Transferrin (Tf) and single chain antibody fragment can target TfR and are typically conjugated to nanomedicines via post-modification, which poses significant production challenges. Here, we report that the polymersomes functionalized with a Tf-binding peptide CGGGHKYLRW (TBP-Ps) can selectively and stably bind Tf and subsequently mediate targeted doxorubicin (Dox) delivery to TfR over-expressing HCT-116 colorectal cancer cells in vitro and in vivo. The Tf surface density of the polymersomes could be controlled by the surface content of TBP. Interestingly, modifying Dox-loaded TBP-Ps with Tf led to greatly increased cellular uptake and inhibitory effect of HCT-116 cells. Tf-bound TBP-Ps demonstrated rapid accumulation in the tumor xenografts in nude mice following i.v. injection. More importantly, Dox-loaded Ps with Tf binding significantly enhanced the antitumor efficacy in mice bearing HCT-116 tumors compared to polymersomes without Tf binding. Surface functionalization of the nanoparticles with Tf-binding peptide provides an appealing strategy in formulating Tf-targeted nanomedicines.

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