P-Glycoprotein Antibody Functionalized Carbon Nanotube Overcomes the Multidrug Resistance of Human Leukemia Cells

Abstract

Multidrug resistance (MDR), which is related to cancer chemotherapy, tumor stem cells, and tumor metastasis, is a huge obstacle for the effective cancer therapy. One of the underlying mechanisms of MDR is the increased efflux of anticancer drugs by overexpressed P-glycoprotein (P-gp) of multidrug resistant cells. In this work, the antibody of P-gp (anti-P-gp) functionalized water-soluble single-walled carbon nanotubes (Ap-SWNTs) loaded with doxorubicin (Dox), Dox/Ap-SWNTs, were synthesized for challenging the MDR of K562 human leukemia cells. The resulting Ap-SWNTs could not only specifically recognize the multidrug resistant human leukemia cells (K562R), but also demonstrate the effective loading and controllable release performance for Dox toward the target K562R cells by exposing to near-infrared radiation (NIR). The recognition capability of Ap-SWNTs toward the K562R cells was confirmed by flow cytometry (FCM) and confocal laser scanning microscopy (CLSM). The binding affinity of Ap-SWNTs toward drug-resistant K562R cells was ca. 23-fold higher than that toward drug-sensitive K562S cells. Additionally, CLSM indicated that Ap-SWNTs could specifically localize on the cell membrane of K562R cells and the fluorescence of Dox in K562R cells could be significantly enhanced after the employment of Ap-SWNTs as carrier. Moreover, the composite of Dox and Ap-SWNTs (Dox/Ap-SWNTs) expressed 2.4-fold higher cytotoxicity and showed the significant cell proliferation suppression toward K562R leukemia cells (p < 0.05) as compared with free Dox which is popularly employed in clinic trials. These results suggest that the Ap-SWNTs are the promising drug delivery vehicle for overcoming the MDR induced by the overexpression of P-gp on cell membrane. Ap-SWNTs loaded with drug molecules could be used to suppress the proliferation of multidrug resistant cells, destroy the tumor stem cells, and inhibit the metastasis of tumor.

Folate and iron difunctionalized multiwall carbon nanotubes as dual-targeted drug nanocarrier to cancer cells

“…Firstly 1 g raw MWCNT were treated in 120 mL concentrated HNO 3 and H 2 SO 4 (1:3, v/v) solution at 120°C in an oil bath for 30 min [34]. After dilution with water by 10-fold, the solution was filtered through a 0.45 lm filter.…”

“…Previously, we have investigated the cellular uptake of oxidized CNTs [33], the detection of intracellular uptake of drug molecules carried by CNTs [4], and the targeted drug delivery of Dox to multidrug resistant leukemia cells by using antibody functionalized SWCNT as nanocarrier [34]. These studies have demonstrated the potential of CNTs to carry drugs into the cells efficiently via endocytosis.…”

Mesoporous carbon biomaterials

“…Of the carbon-family members, sp 2 carbon-based materials such as fullerene [4,5], carbon nanotubes [1,[6][7][8][9][10][11], carbon dots [12][13][14], and graphene [15][16][17][18], have been explored for promising applications in biomedicine, including drug delivery, gene transfection, photothermal therapy, photodynamic therapy, biosensing, and even tissue engineering [19][20][21]. For instance, the hollow space in fullerene/carbon nanotubes and large surface-to-volume ratio of graphene can be used for the encapsulation and intracellular delivery of therapeutic agents.…”

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

“…Such a magnetic responsive delivery system may also be applied for delivering therapeutic nucleic acid (DNA or siRNA), antibodies, growth factors, and recombinant protein to overcome the MDR property of cancer cells. For instance, the Dox‐loaded, P‐gp antibodies (anti‐Pgp) functionalized SWNTs (Ap‐SWNTs) demonstrate high drug loading efficacy and NIR controlled drug release 116. The Ap‐SWNTs were specifically sensitive to MDR human leukemia cells (K562R) with 2.4‐fold higher cytotoxicity and caused significant cell death when against K562R with near‐infrared radiation compared to free Dox, because the P‐gp antibody functionalized SWNTs could effectively interact with P‐gp, which were ubiquitously overexpressed on the membrane surface of MDR cells.…”