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Here, a strategy involving blocking programmed cell death protein 1 (PD\u20101) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA\u2010Psi\u2010DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme\u2010activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP\u20102. It is found that HA\u2010Psi\u2010DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon\u2010\u03b3. This cytokine promotes the expression of programmed cell death protein\u2010ligand 1 (PD\u2010L1) on tumor cells, which will cause immunosuppression after interacting with PD\u20101 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA\u2010Psi\u2010DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti\u2010PD\u20101 antibody (\u03b1\u2010PD1) due to the neutralization of immunosuppression by blocking the interaction between PD\u2010L1 and PD\u20101. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.<\/jats:p>","DOI":"10.1002\/smll.201802403","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:28:59Z","timestamp":1534951739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["PD\u20101 Blockade for Improving the Antitumor Efficiency of Polymer\u2013Doxorubicin Nanoprodrug"],"prefix":"10.1002","volume":"14","author":[{"given":"Fan","family":"Gao","sequence":"first","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry Wuhan University  Wuhan 430072 P. R. 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