Artificial Nanoscale Erythrocytes from Clinically Relevant Compounds for Enhancing Cancer Immunotherapy

Abstract

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 (Eu-FBCP/PTX + aPL).ABSTRACT Because of enhanced efficacy and lower side effects, cancer immunotherapies 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).

Modified Aerotaxy for the Plug-in Manufacture of Cell-Penetrating Fenton Nanoagents for Reinforcing Chemodynamic Cancer Therapy

“…On the other hand, this might make the interaction of macrophages with nanoparticles challenging and provide long-term systemic circulation. 74 Therefore, with the higher degree of internalization through multiple endocytic pathways and the higher rate of invasion with spiky exteriors, an in vitro spheroid penetration assay was conducted to confirm the penetration. Similar to the internalization, higher penetration activities were observed in the nanoagents (Figure 6B).…”

“…The issues at low pH and lysosomal degradation associated with the clathrin-mediated endocytosis might be evaded by the nanoagent following other pathways. On the other hand, this might make the interaction of macrophages with nanoparticles challenging and provide long-term systemic circulation . Therefore, with the higher degree of internalization through multiple endocytic pathways and the higher rate of invasion with spiky exteriors, an in vitro spheroid penetration assay was conducted to confirm the penetration.…”

Emerging Trends in Nano-Driven Immunotherapy for Treatment of Cancer

“…This system caused immunogenic cell death (ICD) and released damage-associated molecular patterns (DAMPs) that accelerated DC maturation and activated effector cells for a robust antitumour immune response [ 24 ]. In another study Europium ions in combination with paclitaxel loaded in concave-shaped eudragit polymer nanoparticles were investigated successfully for chemoimmunotherapy by co-administering anti-PD1 antibodies using in vitro and in vivo models of colon carcinoma [ 25 ].…”

Artificial Macrophage with Hierarchical Nanostructure for Biomimetic Reconstruction of Antitumor Immunity

“…Biomimetics utilizes synthetic materials to mimic the biological functions or processes in nature, which has attracted interdisciplinary research interest [ 1 – 3 ]. As a typical example of biomimetics, artificial cells are constructed from synthetic materials to imitate all or part of the biological functions of natural cells [ 4 ]. The synthetic and tunable structures of artificial cells allow them to adequately exert various physicochemical interactions with cells [ 5 ].…”