Artificial Nanoscale Erythrocytes from Clinically Relevant Compounds for Enhancing Cancer Immunotherapy
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ARTICLE
Cite as Nano-Micro Lett. (2020) 12:90 Received: 17 January 2020 Accepted: 12 March 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00428-y
Artificial Nanoscale Erythrocytes from Clinically Relevant Compounds for Enhancing Cancer Immunotherapy Wenquan Ou1, Kang Sik Nam2, Dae Hoon Park2, Jungho Hwang2 *, Sae Kwang Ku3, Chul Soon Yong1, Jong Oh Kim1 *, Jeong Hoon Byeon4 * Wenquan Ou and Kang Sik Nam have contributed equally to this work * Jungho Hwang, [email protected]; Jong Oh Kim, [email protected]; Jeong Hoon Byeon, [email protected] 1 College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea 2
4 3
School of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea School of Mechanical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
ARTICLE HIGHLIGHTS • A two-phase coaxial electrospray was designed to produce paclitaxel-loaded fake blood cell Eudragit particles (Eu-FBCP/PTX). • The chemo-immunotherapeutic efficacy was further enhanced after combining with anti-programmed death-ligand 1 antibodies (EuFBCP/PTX + aPL).
ABSTRACT Because of enhanced efficacy and lower side effects, cancer immuno-
therapies have recently been extensively investigated in clinical trials to overcome the limitations of conventional cancer monotherapies. Although engineering attempts have been made to build nanosystems even including stimulus nanomaterials for the efficient delivery of antigens, adjuvants, or anticancer drugs to improve immunogenic cancer cell death, this requires huge R&D efforts and investment for clinically relevant findings to be approved for translation of the nanosystems. To this end, in this study, an air–liquid two-phase electrospray was developed for stable bubble pressing under a balance between mechanical and electrical parameters of the spray to continuously produce biomimetic nanosystems consisting of only clinically relevant compounds [paclitaxel-loaded fake blood cell Eudragit particle (Eu-FBCP/PTX)] to provide a conceptual leap for the timely development of translatable chemo-immunotherapeutic nanosystems. This was pursued as the efficacy of systems for delivering anticancer agents that has been mainly influenced by nanosystem shape because of its relevance to transporting behavior to organs, blood circulation, and cell–membrane interactions. The resulting Eu-FBCP/PTX nanosystems exhibiting phagocytic and micropinocytic uptake behaviors can confer better efficacy in chemo-immunotherapeutics in the absence and presence of anti-PD-L1 antibodies than similar sized PTX-loaded spherical Eu particles (Eu-s/PTX). KEYWORDS Cancer immunotherapies; Air–liquid two-phase electrospray; Paclitaxel-loaded fake blood cell Eudragit particle; Translatable chemo-immunotherapeutic nanosystems; Anti-PD-L1 antibodies
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1 Introduction The recent approval of several immune-stimulatable or modulatable formulations to
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