Erythrocyte Membrane Is an Alternative Coating to Polyethylene Glycol for Prolonging the Circulation Lifetime of Gold Nanocages for Photothermal Therapy

Abstract

Gold nanocages (AuNCs), which have tunable near-infrared (NIR) absorption and intrinsically high photothermal conversion efficiency, have been actively investigated as photothermal conversion agents for photothermal therapy (PTT). The short blood circulation lifetime of AuNCs, however, limits their tumor uptake and thus in vivo applications. Here we show that such a limitation can be overcome by cloaking AuNCs with red blood cell (RBC) membranes, a natural stealth coating. The fusion of RBC membranes over AuNC surface does not alter the unique porous and hollow structures of AuNCs, and the resulting RBC-membrane-coated AuNCs (RBC-AuNCs) exhibit good colloidal stability. Upon NIR laser irradiation, the RBC-AuNCs demonstrate in vitro photothermal effects and selectively ablate cancerous cells within the irradiation zone as do the pristine biopolymer-stealth-coated AuNCs. Moreover, the RBC-AuNCs exhibit significantly enhanced in vivo blood retention and circulation lifetime compared to the biopolymer-stealth-coated counterparts, as demonstrated using a mouse model. With integrated advantages of photothermal effects from AuNCs and long blood circulation lifetime from RBCs, the RBC-AuNCs demonstrate drastically enhanced tumor uptake when administered systematically, and mice that received PPT cancer treatment modulated by RBC-AuNCs achieve 100% survival over a span of 45 days. Taken together, our results indicate that the long circulating RBC-AuNCs may facilitate the in vivo applications of AuNCs, and the RBC-membrane stealth coating technique may pave the way to improved efficacy of PPT modulated by noble metal nanoparticles.

Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer

“…[18][19][20] The use of natural cellular membranes to camouflage synthetic polymeric nanoparticles has demonstrated significant potential. [21][22][23][24][25] In this study, the membranes of human cytotoxic T lymphocytes (hCTLs) were chosen to produce cancer-targeting nanoparticles, because of the long blood circulation time and the ability to recruit and localize at tumor sites, of this cell type. 22 Leukocytes have a variety of proteins on their membranes to detect inflammation and diseased tissues.…”

Gold nanoparticles enlighten the future of cancer theranostics

“…150,154,174,175 As an alternative stealth coating material, the membrane of these cells completely covers the NP surface with their "selfmarkers" (ie, proteins, glycans, and acidic sialyl moieties), and the resultant NPs, recognized as the host's own cells, can actively evade the immune system. For example, Piao et al 160 reported that the RBC-coated gold nanocages exhibited longer blood retention compared with the PEGylated counterparts. In addition, the fusion of RBC membranes over gold surface did not alter the unique porous and hollow structures of gold nanocages.…”

Cell membrane-coated nanoparticles for tumor-targeted drug delivery

“…Based on a two-compartment model, the RBCNPs possessed a significantly longer systemic circulation than PEGylated PLGA nanoparticles, the elimination half time of RBCNPs was 39.6 h and that of PEGylated nanoparticles was only 15.8 h [28]. A similar result was provided by the comparison between gold nanocages (AuNCs) and RBC membrane coated AuNCs (RBC-AuNCs) [32]. The RBC-AuNCs possessed a nearly ten-fold in vivo circulation lifetime than the poly(vinylpyrrolidone)-coated AuNCs.…”