Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma

Abstract

Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood–brain barrier and the blood–brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood–brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood–brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.

Research update on cell membrane camouflaged nanoparticles for cancer therapy

“…Red blood cell (Hu et al, 2011;Pei et al, 2018;Wan et al, 2018;Xuan et al, 2018;Bidkar et al, 2019;Huang et al, 2019;Lee et al, 2019;Wang et al, 2020a;Wang et al, 2020c;Li and Zhang, 2020;Peng et al, 2020;Zhai et al, 2020;Wu et al, 2021b;Gao et al, 2021) Hu et al, Wang et al, Li et al, Lee et al, Wu et al, Huang et al, Xuan et al, Peng et al, Bidkar et al, Wang et al, Wan et al, Zhai et al, Pei et al, Gao et al Platelet (Xu et al, 2018;Chen et al, 2019;Wang et al, 2019;Jiang et al, 2020b;Wu et al, 2020;Li et al, 2021a;Lyu et al, 2021) Wu et al, Li et al, Chen et al, Wang et al, Jiang et al, Lyu et al, Xu et al Neutrophil (Wang et al, 2021a;Zhao et al, 2021b;Zhang et al, 2021) Zhang et al, Wang et al, Zhao et al Cancer cell (Jiang et al, 2020a;Wang et al, 2020b;Wang et al, 2020d;Chen et al, 2021a;Zhao et al, 2021a;Fan et al, 2021;Jin et al, 2021;Liu et al, 2021;Shen et al, 2021;Xu et al, 2021) Wang et al, Liu et al, Li et al, Chen et al, Zhao et al, Shen et al, Fan et al, Jiang et al, Wang et al, Jin et al, Xu et (Parodi et al, 2013;Evangelopoulos et al, 2016;Palomba et al, 2016;Molinaro et al, 2018;…”

“…Cell membranes that separate the cell cytoplasm from the outer environment are phospholipid bilayer semi-permeable structures with embedded and bound proteins and other motifs. The isolation of plasma membranes from source cells mainly involves a combination of hypotonic lysis, mechanical membrane fragmentation, and emptying the intracellular contents through differential centrifugation (Parodi et al, 2013;Gao et al, 2016;Zhang et al, 2017;Pitchaimani et al, 2018;Yang et al, 2018;Cao et al, 2020;Gong et al, 2020;Poudel et al, 2020;Wu et al, 2020;Chen et al, 2021a;Li et al, 2021a;Wang et al, 2021a;Zhao et al, 2021a;Wu et al, 2021c;Fan et al, 2021;Liu et al, 2021;Shen et al, 2021;Zhang et al, 2021). Generally, cell membrane vesicles used for core NPs coating are obtained using a combination of hypotonic lysis buffer to lyse cells or the freeze-thaw method to obtain cell membranes; mechanical disruption of cell membranes using a dounce homogenizer, sonication, and/or extrusion, and finally, differential ultracentrifugation to obtain membrane vesicles (Parodi et al, 2013;Gao et al, 2016;Zhang et al, 2017;Liu et al, 2018;Pitchaimani et al, 2018;Xuan et al, 2018;Yang et al, 2018;Bidkar et al, 2019;Huang et al, 2019;Lee et al, 2019;Wang et al, 2020b;Cao et al, 2020;Wang et al, 2020c;Peng et al, 2020;Poudel et al, 2020;Wu et al, 2020;Chen et al, 2021a;…”

“…The core constituents of cell membrane-camouflaged NPs can be organic, inorganic, or organic-inorganic hybrid nanosystems (Attia et al, 2019;Dash et al, 2020;Wu et al, 2021a;Castro et al, 2021;Jha et al, 2021). Typically, the core of the NP, which must be delivered and released at the target site, consists of its therapeutic agent and framework, which are shielded by cell membranes isolated from source cells (Gao et al, 2016;Zhang et al, 2017;Pitchaimani et al, 2018;Yang et al, 2018;Cao et al, 2020;Gong et al, 2020;Poudel et al, 2020;Wu et al, 2020;Chen et al, 2021a;Li et al, 2021a;Wang et al, 2021a;Zhao et al, 2021a;Wu et al, 2021c;Fan et al, 2021;Shen et al, 2021). Frontiers in Bioengineering and Biotechnology frontiersin.org Pitchaimani et al, 2018;Bidkar et al, 2019;Wang et al, 2019;Cao et al, 2020;Poudel et al, 2020;Wu et al, 2020;Wang et al, 2021a;Liu et al, 2021;Ma et al, 2021;Zhang et al, 2021;Cai et al, 2022).…”

“…Biomimetic NPs consist of either material-based core NPs coated the biomimetic membrane or biomimetic membrane itself acting as a therapeutic cargo carrier (Attia et al, 2019;Dash et al, 2020;Jha et al, 2021). Biomimetic NPs camouflaged with cell membrane can exhibit cell-like behaviors, potentially affording them a prolonged circulation time (Hu et al, 2011;Liu et al, 2018;Xuan et al, 2018;Bidkar et al, 2019;Huang et al, 2019;Lee et al, 2019;Wang et al, 2020a;Wang et al, 2020b;Wang et al, 2020c;Dash et al, 2020;Li and Zhang, 2020;Peng et al, 2020;Wu et al, 2021b), immune escape (Pitchaimani et al, 2018;Cao et al, 2020;Wang et al, 2021a;Liu et al, 2021;Zhang et al, 2021), and/or increased targeting abilities (Parodi et al, 2013;Gao et al, 2016;Zhang et al, 2017;Pitchaimani et al, 2018;Yang et al, 2018;Bidkar et al, 2019;Cao et al, 2020;Wang et al, 2020c;Gong et al, 2020;Poudel et al, 2020;Wu et al, 2020;Chen et al, 2021a;Li et al, 2021a;Wang et al, 2021a;Zhao et al, 2021a;Wu et al, 2021c;Fan et al, 2021;Liu et al, 2021;Shen et al, 2021;Zhang et al, 2...…”

“…The first to be developed biomimetic NPs were red blood cell (RBC) membrane-camouflaged NPs (Hu et al, 2011;Huang et al, 2019;Castro et al, 2021). Since the successful proof-ofconcept study that using cloaking NPs with cellular membranes isolated from freshly harvested erythrocytes and transferring bioactive cellular components to the surface of synthetic materials in order to confer unique functions not otherwise attainable through other bioconjugation techniques a decade ago, many source cells have been used for the fabrication of cellular membrane-camouflaged NPs (Table 1), including erythrocytes (Hu et al, 2011;Liu et al, 2018;Xuan et al, 2018;Huang et al, 2019;Lee et al, 2019;Wang et al, 2020a;Li and Zhang, 2020;Peng et al, 2020;Wu et al, 2021b), neutrophils (Wang et al, 2021a;Zhang et al, 2021), macrophages (Parodi et al, 2013;Cao et al, 2020;Poudel et al, 2020), natural killer (NK) cells (Pitchaimani et al, 2018), cytotoxic T cells (Zhang et al, 2017), stem cells (Gao et al, 2016;Yang et al, 2018), platelets (Wu et al, 2020;Li et al, 2021a), and cancer cells Chen et al, 2021a;Zhao et al, 2021a;Fan et al, 2021;Shen et al, 2021).…”