Work

Improved Cancer Immunochemotherapy via Optimal Co-delivery of Chemotherapeutic and Immunomodulatory Agents

Year: 2018

Type: article

Abstract: It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG 2k -Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX). Although antitumor immune responses were enhanced with a PTX-loaded nanocarrier, the accumulation of myeloid-derived suppressor cells (MDSCs) was also significantly increased, which may limit the overall efficacy of therapy. In the present work, we developed an improved dual-functional nanocarrier (PEG 5k -Fmoc-NLG 2 ) to co-load PTX and sunitinib (SUN, a multitarget receptor tyrosine kinase inhibitor) for improved cancer immunochemotherapy. We found that the recruited MDSCs negatively impacted the overall antitumor activity of the PTX-loaded PEG-NLG nanocarrier. Mechanistic study suggests that this is likely attributed to the PTX-mediated induction of a number of chemokines that are involved in the recruitment of MDSCs. We have further shown that the induction of these chemokines was drastically blocked by SUN. Co-delivery of PTX and SUN via the PEG 5k -Fmoc-NLG919 2 nanocarrier led to a further improvement in the therapeutic efficacy with a concomitant reduction in MDSCs.

Source: Molecular Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.8b00717

Authors: Yichao Chen, Jingjing Sun, Yixian Huang, Binfeng Lu, Song Li

Institution: University of Pittsburgh

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Shear Family Foundation, National Institutes of Health, National Cancer Institute