A dual-targeting drug delivery and pH-sensitive controlled release system based on multifunctionalized graphene oxide (GO) was established in order to enhance the effect of targeted drug delivery and realize intelligently controlled release. A superparamagnetic GO-Fe 3 O 4 nanohybrid was firstly prepared via a simple and effective chemical precipitation method. Then folic acid, a targeting agent toward some tumor cells, was conjugated onto Fe 3 O 4 nanoparticles via the chemical linkage with amino groups of the 3-aminopropyl triethoxysilane (APS) modified superparamagnetic GO-Fe 3 O 4 nanohybrid, to give the multi-functionalized GO. Doxorubicin hydrochloride (Dox) as an anti-tumor drug model was loaded onto the surface of this multi-functionalized GO via p-p stacking. The drug loading capacity of this multi-functionalized GO is as high as 0.387 mg mg À1 and the drug release depends strongly on pH values. Cell uptake studies were carried out using fluorescein isothiocyanate labeled or Dox loaded multi-functionalized GO to evaluate their targeted delivery property and toxicity to tumor cells. The results show that this multi-functionalized GO has potential applications for targeted delivery and the controlled release of anticancer drugs.

An elevated number of Gr-1 + CD11b + myeloid cells has been described in mice bearing transplantable tumors, and has been associated with immune suppression. We examined the role of such myeloid suppressor cells in mice bearing the spontaneously transformed syngeneic mouse ovarian surface epithelial cell line, 1D8. We observed high levels of CD80 expression by Gr-1 + CD11b + cells from spleen, ascites, and tumor tissue of mice bearing 1D8 ovarian carcinoma, whereas CD40 and CD86 were absent. CD80 expression was not detected on Gr-

Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl À functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl À was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNTcomplexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl À could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl À functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene.The -CONH-(CH 2 ) 6 -NH 3 + Cl À functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.