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.

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Water-soluble multiwalled carbon nanotubes (MWNTs) with temperature-responsive shells were synthesized by grafting poly(N-isopropylacrylamide) (PNIPAAM) from sidewall of MWNT via surface reversible addition and fragmentation chain transfer (RAFT) polymerization using RAFT agent functionalized MWNT as chain transfer agent. Carboxylic groups on MWNT were formed by nitric acid oxidation. Then bromoisobutyrate groups were covalently attached to the MWNT by esterification of 2-hydroxyethyl-2‘-bromoisobutyrate with carboxylic groups, forming bromoisobutyrate functionalized MWNT (MWNT-Br). RAFT agent functionalized MWNT was produced by substitute reaction of MWNT-Br with PhC(S)SMgBr. 1H NMR, FT-IR, and thermogravimetric analyses (TGA) results showed that PNIPAAM chains grew from MWNT by surface reversible addition fragmentation chain transfer polymerization. The molecular weight of PNIPAAM on MWNT increased linearly with monomer conversion, and its PDI is narrow (around 1.3). TGA showed that the amount of PNIPAAM grown from the MWNT increased with the increase of polymerization time. The MWNT-g-PNIPAAM has good solubility in water, chloroform, and tetrahydrofuran. TEM images also showed the MWNT-g-PNIPAAM was dispersed individually, indicating that the bundles of original MWNT were separated into individual tubes by surface RAFT polymerization. The produced MWNT-g-PNIPAAM has a PNIPAAM shell, which is very sensitive to change of temperature. This method can also be employed to graft other functional polymer chains onto MWNTs.