Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment

Abstract

Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting.

Keywords:

• Chondroitin sulfate A
• CSA-bind peptide
• nanoparticles
• drug delivery
• tumor targeting
• choriocarcinoma

Disclosure statement

X.F., B.Z., and J.Z. are the inventors on the patent application PCT/CN2017/108646 submitted by SIAT that covers a targeted delivery of drugs for human cancer treatment and application. No potential conflicts of interest were disclosed by the other authors.

Additional information

Funding

This work was supported by grants from the National Key R&D Program of China [2016YFC1000402], the National Natural Science Foundation [81571445], and the Natural Science Foundation of Guangdong Province [2016A030313178] for X.F.; the Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Disease [2013A061401013] for S.L. and X.F.; the Shenzhen Basic Research Fund [JCYJ20150521094519488] for X.F and [JCYJ20170413165233512] for J.Z. and X.F.; the Public Welfare Project of Guangdong Province [2017A020211033] for J.Z., the Natural Science Foundation of Research Team [2016A030312006], and the Shenzhen Science and Technology Program [JCYJ20150521094519473 and JCYJ20160429191503002] for L.C.