What are carbon nanotubes’ roles in anti-tumor therapies?

Abstract

Since their discovery, carbon nanotubes (CNTs) have become one of the most promising nanomaterials in many industrial and
biomedical applications. Due to their unique physicochemical properties, CNTs have been proposed and actively exploited as
multipurpose innovative carriers for cancer therapy. The aim of this article is to provide an overview of the status of applications,
advantages, and up-to-date research and development of carbon nanotubes in cancer therapy with an emphasis on drug delivery,
photothermal therapy, gene therapy, RNAi, and immune therapy. In addition, the issues of risk and safety of CNTs in cancer
nanotechnology are discussed briefly.

Keywordscarbon nanotubes-tumor-therapy-delivery-immune

Full text

SCIENCE CHINA
Chemistry
© Science China Press and Springer-Verlag Berlin Heidelberg 2010 chem.scichina.com www.springerlink.com
*Corresponding author (email: xuhy@pumc.edu.cn)
• ARTICLES • November 2010 Vol.53 No.11: 1–7
doi: 10.1007/s11426-010-4117-6
What are carbon nanotubes’ roles in anti-tumor therapies?
XU HaiYan*, MENG Jie & KONG Hua
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
Received May 12, 2010; accepted July 4, 2010
Since their discovery, carbon nanotubes (CNTs) have become one of the most promising nanomaterials in many industrial and
biomedical applications. Due to their unique physicochemical properties, CNTs have been proposed and actively exploited as
multipurpose innovative carriers for cancer therapy. The aim of this article is to provide an overview of the status of applica-
tions, advantages, and up-to-date research and development of carbon nanotubes in cancer therapy with an emphasis on drug
delivery, photothermal therapy, gene therapy, RNAi, and immune therapy. In addition, the issues of risk and safety of CNTs in
cancer nanotechnology are discussed briefly.
carbon nanotubes, tumor, therapy, delivery, immune
1 Introduction
In the continuous fight against cancer, there are many chal-
lenges that reduce the efficiency of existing antitumor
therapies such as serious side effects of chemotherapy, mul-
tidrug resistance (MDR) and immune escape mechanisms of
tumor cells. In recent years, rapid advances in nanoparti-
cle-based delivery systems have provided promising new
ways to overcome those challenges. Among the various
nanoparticles, carbon nanotubes (CNTs) have recently gar-
nered intense research interest and have shown attractive
performance in various aspects of antitumor therapies.
CNTs have a unique structure on the nanoscale that al-
lows them to enter cells easily and to conjugate various
therapeutic molecules. Additionally, their pure carbon
composition makes them possess good biocompatibility. In
light of these factors, CNTs have become a new class of
promising candidates for a delivery system. This review
attempts to provide insight into the current research pro-
gress using CNTs for cancer therapy.
2 The role of CNTs in chemotherapy
Chemotherapy is currently one major strategy to fight can-
cers. However, patients have to be administered a combina-
tion of drugs that increase in dose over time, which results
in severe side effects, including toxicity and multidrug re-
sistance (MDR). Hence, development of new delivery vehi-
cles to transport chemotherapeutic reagents into tumor cells
with high efficiency is necessary to overcome drug resis-
tance as well as to reduce side effects. An emerging ap-
proach is to utilize nanotechnology to optimize the existing
chemotherapies. Carbon nanotube-based drug delivery has
shown a promise in tumor-targeted accumulation in mice,
and the system exhibits good biocompatibility, good excre-
tability, and little toxicity. Various chemotherapeutic re-
agents have been demonstrated to have increased efficiency
after being chemically linked to CNTs.
2.1 Delivery of chemotherapeutic drugs by carbon
nanotubes
Paclitaxel (PTX) is one of the most widely used cancer
chemotherapy drugs. When PTX was conjugated to branched

2 XU HaiYan, et al. Sci China Chem November (2010) Vol.53 No.11
polyethylene glycol chains on single-walled carbon nano-
tubes (SWNTs) via a cleavable ester bond, the SWNT-PTX
affords higher efficacy in suppressing tumor growth than
clinical Taxol in a murine 4T1 breast cancer model. The
improvement is owing to the prolonged circulation in the
blood and a 10-fold higher PTX uptake by the tumor when
delivered by SWNTs (likely because of an enhanced per-
meability and retention (EPR) effect). Drug molecules car-
ried into the reticuloendothelial system are released from
SWNTs and excreted via the biliary pathway without caus-
ing apparent toxic effects to normal organs [1]. Multiwalled
carbon nanotubes (MWNTs) perform similarly when carry-
ing chemotherapeutic reagents into tumor cells. When anti-
tumor reagent 10-hydroxycamptothecin (HCPT) was linked
to MWNTs covalently through a cleavable ester linkage
using hydrophilic diaminotriethylene glycol as the spacer
between the nanotube and drug moieties, the obtained
MWNT- HCPT conjugates were found to be superior to the
clinical HCPT formulation in antitumor activity both in vi-
tro and in vivo [2]. The MWNT-HCPT conjugates also have
relatively long circulation in the blood and high drug accu-
mulation at the tumor site. These properties together with
the enhanced cellular uptake and the multivalent presenta-
tion of HCPT on a single nanotube substantially benefit the
antitumor effects.
It is noteworthy that the cytotoxicity of chemotherapeutic
reagents has been demonstrated to be associated with the
linkers that combine drug molecules to CNTs. When meth-
otrexate was tethered to MWNTs through different cleav-
able linkers, for example, the conjugates were internalized
by human breast cancer cells, the initial investigations using
such conjugates indicated that the activity of the drug
strongly depends on the type of the linker used. High cyto-
toxic activity could be observed when using an enzyme-
sensitive peptide linker [3]. For example, single-walled
carbon nanotubes (SWNTs) were conjugated to a doxorubi-
cin prodrug via a carbamate linker that cleaves enzymati-
cally to allow temporal release of the active drug. The con-
jugate was rapidly internalized into the lysosomes of mela-
noma cells and was retained in the subcellular compartment
for over 24 h. The conjugate induced time-dependent cell
death in B16-F10 melanoma cells in vitro and inhibited
melanoma tumors in vivo without the systemic side effects
associated with free doxorubicin [4].
Physical combination is another effective way to deliver
chemotherapeutic reagents. It is theorized that drug mole-
cules can physically conjugate with CNTs via pi-pi stacking
to form supramolecular complexes with the aromatic chro-
mophore and enhance their cytotoxic activity [5, 6]. Immer-
sion of poly (ethylene glycol)-graft-SWNTs (PEG-g-SWNTs)
or PEG-graft-MWNTs (PEG-g-MWNTs) in a saturated so-
lution of PTX in methanol can achieve physical loading of
PTX onto CNTs. Both PTX-loaded PEG-g-SWNTs and
PTX-loaded PEG-g-MWNTs are highly efficient in killing
HeLa and MCF-7 cells [7]. PEG-doxorubicin conjugate
(PEG-DXR) was adsorbed onto oxidized single-wall carbon
nanohorns (oxSWNHs). The intratumorally administered
PEG-DXR-bound oxSWNHs caused a significant retarda-
tion in tumor growth associated with the prolonged DXR
retention in the tumor. In accordance with this DXR reten-
tion, a large number of oxSWNH agglomerates were found
from the periphery of the tumor to the axillary lymph node,
which is a major site of breast cancer metastasis near the
tumor, possibly by means of interstitial lymphatic-fluid
transport [8].
Another strategy to load chemotherapeutic reagents
physically is to fill the drugs into the tubes. For example,
CNTs can carry the antitumor drugs cisplatin and car-
boplatin inside by using a nanoprecipitation method or a
wet-chemical approach after the CNTs were opened [9, 10].
The conjugates were observed adhering to the cell surfaces
in vitro and stayed within the tumor tissues in vivo, which
implies that the drugs were released from the CNTs in high
concentrations locally at the cells in vitro and in the tissues
in vivo and could efficiently attack the tumor cells. When
intratumorally injected into the transplanted tumors of mice,
the conjugate suppressed the tumor growth more than intact
cisplatin. However, compared with the chemical binding
and physical adsorption methods mentioned above, filling
drugs into CNTs has not been widely employed partially
because the preparation is intricate and the release mecha-
nism from the CNTs is still unknown. It is also noted that in
some studies researchers found that CNTs themselves had
an in vivo anticancer effect in addition to significantly en-
hancing the chemotherapeutic effects of the drugs [9, 11].
2.2 Tumor-targeting carbon nanotubes in chemotherapy
A long-standing problem in cancer chemotherapy is the lack
of tumor-specific treatments. Cytotoxic reagents have very
little or no specificity, which leads to systemic toxicity and
causes undesirable severe side effects. CNTs passively re-
alize their targeting function due to the EPR effect of the
nanoparticles; therefore, specificity is still one main obsta-
cle in targeting the delivery of antitumor drugs. Addition-
ally, the lack of tumor-specific markers stands as another
big challenge. Therefore, the development of innovative and
efficacious tumor-specific drug delivery protocols or sys-
tems is urgently needed to fight against various cancer types,
especially multidrug-resistant tumors.
Usually tumor cells overexpress some tumor associated
antigens (TAA) and/or tumor specific antigens (TSA) that
can be used as targets to deliver cytotoxic agents into tu-
mors. Accordingly, the types of targeting molecules mainly
include peptides, proteins, and small chemical molecules
such as folate. The transporting capabilities of CNTs com-
bined with antibodies that recognize tumor-associated pro-
teins or receptors may further improve the efficiency and
reduce the toxic side effects of chemotherapeutic reagents.
One example of a targeting protein is HER2. Recom-

XU HaiYan, et al. Sci China Chem November (2010) Vol.53 No.11 3
bined ricin A chain protein (RTA) is a toxin protein that
induces cell death. When coupled with HER2, the delivery
of RTA via nanotube carriers can selectively recognize the
HER2/neu receptor on certain breast cancer cells and induce
targeted destruction of the tumor cells [12]. Receptors of
various growth factors are other possible protein targets on
the tumor cells. When cisplatin and epidermal growth fac-
tors (EGF) were attached to SWNTs to specifically target
squamous cancer, the SWCNT-cisplatin-EGF was selec-
tively taken up by the HNSCC tumors of mice. Most sig-
nificantly, regression of tumor growth was rapid in mice
treated with targeted SWNT-cisplatin-EGF relative to non-
targeted SWNT-cisplatin [13].
Folic acid (FA) is a targeting molecule for many tumors
as the folate receptor (FR) is overexpressed across a broad
spectrum of human tumors. Most low-molecular-weight
platinum anticancer drugs have short blood circulation
times. Researchers chemically conjugated a platinum (IV)
complex containing a folate derivative at an axial position
to the surface of amine-functionalized SWNTs. The SWNTs
deliver the folate-bearing Pt (IV) cargos into FR (+) cancer
cells by endocytosis. Once inside the cell, cisplatin, formed
upon reductive release from the SWNTs, enters the nucleus
and reacts with the nuclear DNA to which it is targeted [14].
A combination of FA modification with magnetic CNTs
may facilitate the targeted delivery of drugs in the lym-
phatic tissue more effectively. Chemotherapeutic agents
were incorporated into the pores of functionalized magnetic
CNTs, and FA was non-covalently conjugated to the mag-
netic CNTs. By using an externally placed magnet to guide
the drug matrix to the region of the targeted lymph nodes,
the magnetic CNTs can be retained in the draining lymph
nodes for several days while continuously releasing chemo-
therapeutic drugs [15]. FA coupling can be combined with
pH sensitive modifications in CNTs. Polysaccharide coating
and FA modification of SWNTs form a dual-targeting de-
livery system that can selectively deliver DOX into HeLa
cells and release the drug in the lysosomes at low pH with a
much higher efficiency to damage the nuclear DNA and
inhibit cell proliferation [16].
2.3 Using carbon nanotubes to overcome multidrug
resistance
Multidrug resistance (MDR), which is related to cancer
chemotherapy, tumor stem cells, and tumor metastasis, is a
huge obstacle for effective cancer therapy. One of the un-
derlying mechanisms of MDR is the increased efflux of
anticancer drugs by overexpressed P-glycoprotein (P-gp) in
multidrug resistant cells. To overcome MDR in K562 hu-
man leukemia cells, functionalized water-soluble SWNTs
conjugated to the antibody of P-gp (Ap) and loaded with
doxorubicin (Dox), or Dox/Ap-SWNTs, were synthesized.
The binding affinity of Ap-SWNTs toward drug-resistant
K562R cells was 23-fold higher than that toward drug-
sensitive K562S cells. Additionally, Ap-SWNTs could spe-
cifically localize on the cell membrane of K562R cells, and
the amount of Dox in K562R cells could be significantly
enhanced when Ap-SWNTs were employed as a carrier.
Moreover, the Dox/Ap-SWNTs expressed 2.4-fold higher
cytotoxicity and showed a significant suppression of cell
proliferation for K562R leukemia cells as compared to free
Dox [17].
3 CNTs help physical treatments to kill tumor cells
3.1 CNTs’ synergic role with NIR irradiation
Photothermal therapy using nanomaterials has recently at-
tracted interest as an efficient strategy for the next genera-
tion of cancer treatments. Hyperthermia therapy is one op-
tional solution for cancer treatment especially for some
kinds of solid malignant tumors such as liver and breast
tumors. CNTs are unique materials that absorb infrared ra-
diation (IR) especially between 700 and 1100 nm where
body tissues, including skin, are most transparent. This in-
trinsic property of CNTs can be used to optically stimulate
nanotubes located inside living cells to afford multifunc-
tional nanotube biological transporters.
SWNTs are an up-and-coming, potent candidate to be a
photothermal therapeutic agent because they generate sig-
nificant amounts of heat upon excitation with near-infrared
light. Continuous NIR radiation can cause cell death be-
cause of excessive local heating of SWNTs. Such a photo-
thermal effect can be employed to induce thermal cell death
in a noninvasive manner. Combined treatments using SWNTs
and NIR irradiation completely destroyed the tumors with-
out harmful side effects or recurrence of the tumors over six
months in the tumor-loaded mice while the tumors treated
in other control groups grew continuously until the death of
the mice. Most of the injected SWNTs were almost com-
pletely excreted from the bodies of the mice in about 2
months through either the biliary or urinary pathway [18].
MWNTs also strongly absorb near-infrared radiation and
efficiently convert the absorbed energy into released heat.
MWNTs can be stimulated with NIR irradiation to destroy
Erlich ascitic carcinoma (EAC) cells [19] and cervical can-
cer HeLa cells [20]. It was demonstrated that the addition of
MWNTs to a suspension of tumor cells results in the photo-
ablative destruction of cells exposed to short time NIR irra-
diation. The use of MWNTs to generate NIR-induced heat
also led to the thermal destruction of kidney cancers in vitro
and in vivo with minimal local toxicity and no evident sys-
temic toxicity, which was demonstrated through magnetic
resonance temperature-mapping and heat shock protein-
reactive immunohistochemistry [21, 22].
3.2 Drug-loading or targeting carbon nanotubes in
cancer photothermal therapy
A combination of the chemotherapeutic agents oxaliplatin

4 XU HaiYan, et al. Sci China Chem November (2010) Vol.53 No.11
or mitomycin C and rapid heating stimulated by IR has
shown effectiveness in killing colorectal cancer cells. This
approach may be used as a rapid bench-to-bedside clinical
therapeutic agent with a significant impact in the localiza-
tion of chemotherapy agents during the surgical manage-
ment of peritoneal dissemination of colorectal cancer [23].
Filling CNTs with magnetic materials offers the potential
for hyperthermia applications [24].
Specificity is also necessary for CNTs used in the ther-
mal ablation of cancers. The transporting capabilities of
CNTs combined with suitable functionalization chemistry
and their intrinsic optical properties can lead to new classes
of novel nanomaterials for the photothermal therapy of
cancer. CNTs attached to antibodies or peptides represent a
typical approach to targeting cancer cells. For example, to
target disialoganglioside (GD2) specifically, which is over-
expressed on the surface of neuroblastoma stNB-V1 cells,
GD2 monoclonal antibody (anti-GD2) was conjugated to
acidified CNTs. The anti-GD2-linked CNTs were exten-
sively internalized by neuroblastoma cells via GD2-mediated
endocytosis. In addition, the anti-GD2 bound CNTs were
not ingested by PC12 cells, which had no GD2 expression.
After NIR laser exposure, stNB-V1 cells were all found to
undergo necrosis while non-GD2 expressing PC12 cells all
remained viable [25]. CD22, which is broadly expressed on
human B cell lymphomas, and HER2, which is usually
overexpressed on various tumor cells, are other representa-
tive proteins that can be targeted by CNTs [26–28].
Conjugated with folate and irradiated by a 980-nm laser
[29] or a 1064-nm Q-switched millisecond pulsed laser [30],
the modified SWNTs effectively enhanced the photothermal
destruction of tumor cells and noticeably spared nontargeted
normal cells. Selective cancer cell destruction can be
achieved by functionalization of SWNTs with a folate moi-
ety followed by selective internalization of SWNTs inside
cells labeled with folate receptor tumor markers and NIR-
triggered cell death without harming receptor-free normal
cells [31]. DNA-encasement has been reported to increase
heat emission following NIR irradiation of MWNTs, and
DNA-encased MWNTs can be used to safely eradicate a
tumor mass in vivo. Upon irradiation, DNA-encasement
resulted in a 3-fold reduction in the concentration of MWNTs
required to impart a 10 °C temperature increase in bulk solu-
tion. A single treatment consisting of intratumoral injection
of MWNTs followed by 2.5 W/cm2 of laser irradiation at 1064
nm completely eradicated PC3 xenograft tumors in 100%
(8/8) of nude mice. Tumors that received only the MWNTs
injection or the laser irradiation showed growth rates indis-
tinguishable from untreated control tumors. Nonmalignant
tissues displayed no long-term damage from treatment [32].
3.3 Carbon nanotubes enhance the efficacy of other
physical cancer treatments
SWNTs have shown their ability to release heat when
placed in a radiofrequency (RF) field, which has been used
to produce thermal cytotoxicity in three human cancer cell
lines. The RF field induced the efficient heating of aqueous
suspensions of SWNTs. Direct intratumoral injection of
SWNTs in vivo followed by immediate RF field treatment
was tolerated well by rabbits bearing hepatic VX2 tumors.
At 48 h, all SWCNT-treated tumors demonstrated complete
necrosis whereas control tumors that were treated with RF
but without SWNTs remained completely viable. Tumors
that were injected with SWNTs but not treated with RF
were also viable [33].
SWNTs have also shown the potential to enhance dielec-
tric contrast between malignant and normal tissues during
microwave detection of breast cancer, and they facilitate
selective heating of malignant tissue for microwave hyper-
thermia treatment of breast cancer. At SWNT concentra-
tions of less than 0.5% by weight, significant increases in
the relative permittivity and effective conductivity could be
observed, which led to a significantly greater temperature
increase in microwave heating experiments. This work is a
first step toward the development of functionalized, tu-
mor-targeting SWNTs as integrated therapeutic and diag-
nostic agents for microwave breast cancer detection and
treatment [34].
4 Carbon nanotubes in antitumor gene therapy
Gene therapy and RNAi have presented great potential for
antitumor treatment. However, gene therapy relies on the
efficient and nontoxic transport of therapeutic genetic
medicine through the cell membranes. Recent studies have
reported that CNTs can deliver a large amount of therapeu-
tic agents, including DNA and RNA, to the target disease
sites. In addition, due to their unparalleled optical and elec-
trical properties, CNTs can deliver DNA/siRNA into cells
including some difficult-to-transfect primary-immune cells
and bacteria; they can also lead to controlled release of
DNA/siRNA for targeted gene therapy. Furthermore, due to
their wire shaped structure (with a diameter matching that
of DNA/siRNA) and their remarkable flexibility, CNTs can
influence the conformational structure and the transient
conformational changes of DNA/RNA, which can further
enhance the therapeutic effects of DNA/siRNA. Synergistic
combinations of the CNT’s capabilities to deliver DNA/
siRNAs will lead to the development of powerful multi-
functional nanomedicine to treat cancer [35].
The ability to obtain a biological response to SWNT/
siRNA complexes has been seen in a variety of cancer cell
types. By noncovalently conjugating unmodified siRNA with
pristine SWNTs, the conjugates containing siRNA targeted
to hypoxia-inducible factor 1 alpha (HIF-1alpha) showed
strong specific inhibition of cellular HIF-1alpha activity.
Moreover, intratumoral administration of SWCNT-HIF-
1alpha siRNA complexes in mice bearing MiaPaCa-2/HRE

XU HaiYan, et al. Sci China Chem November (2010) Vol.53 No.11 5
tumors significantly inhibited the activity of tumor HIF-
1alpha [36]. Another example is the treatment of a human
lung carcinoma model in vivo using siRNA sequences,
which led to cytotoxicity and cell death using amino-func-
tionalized multiwalled carbon nanotubes (MWNT-NH3
+).
The MWNT-NH3
+:siRNA complexes administered intratu-
morally can elicit delayed tumor growth and increase sur-
vival of xenograft-bearing animals, which is believed to
activate biologically in vivo by triggering an apoptotic cas-
cade that leads to extensive necrosis of the human tumor
mass followed by a concomitant prolongation of survival of
human lung tumor-bearing animals [37].
Cyclin A(2) plays a critical role in DNA replication,
transcription, and cell cycle regulation. It is overexpressed
by many types of cancers including leukemia, which sug-
gests that suppression of cyclin A(2) would be an attractive
strategy to prevent tumor progression. Research results
show that functionalized SWNTs can facilitate the coupling
of siRNA that specifically targets human cyclin A(2) to
form cyclin A(2) siRNA-f-SWNTs complexes. These func-
tionalized SWNTs readily enter K562 cells resulting in the
suppression of cyclin A(2) expression. This provides new
insights into additional therapeutic options for chronic
myelogenous leukemia beyond chemotherapy in light of
increasing multidrug resistance [38]. With the aim of im-
proving the amount and delivery efficiency of genes carried
by carbon nanotubes into human cancer cells, different gen-
erations of polyamidoamine dendrimers were used to mod-
ify MWNTs. The modified CNTs can be fully conjugated
with antisense c-myc oligonucleotides (asODN). The resul-
tant conjugate of asODN-MWNTs entered tumor cells
within 15 min (including human breast cancer MCF-7 cells,
MDA-MB-435 cells, and liver cancer HepG2 cells), inhib-
ited the cells’ growth in a time- and dose-dependent manner,
and down-regulated the expression of the c-myc gene and
C-Myc protein [39].
5 CNTs’ role in cancer immune therapy
The significance of immunotherapy as an adjuvant anti-
cancer treatment has been well recognized [40–42]. While
chemotherapy faces the issues of accumulative toxicity and
drug resistance, anti-tumor immunotherapy usually has few
adverse effects, good patient tolerance, and the potential to
improve the prognosis significantly [43]. Some clinical tri-
als of immunotherapy achieved promising results in treating
malignancies such as melanoma, malignant glioma, or renal
cell carcinoma, which tended to respond poorly to chemo-
therapies [44–47]. However, the efficacy of current immu-
notherapy generally needs further improvement.
Tumor development and anti-tumor mechanisms of the
host are critical issues with large complexity and big chal-
lenges. Cancer cells often develop immune tolerance and
immune escape mechanisms [48, 49]; therefore, the anti-
tumor activities of the immune cells in tumor-bearing hosts
are at a very low level, which allows most tumor cells to
escape the immune system [50]. To mount an anti-cancer
immune reaction, one area of particular interest is CNTs’
role in modulating immunological functions. It has been
reported that functionalized CNTs are non-cytotoxic to im-
mune cells [51]. In previous work, we have investigated the
immunological responses that MWNTs may induce in a
tumor-bearing mice model via a local administration of
subcutaneous injection, and we explored the possibility of
utilizing the immune responses to modify the progress of
tumor progression. We have demonstrated that the subcuta-
neously injected water-soluble MWNTs (wsMWNT) can
act as an immunostimulatory substance in the tumor-bearing
mice. They induced significant activation of the comple-
ment system, increased cytokine production, and led to
macrophage cell activation. All of these immune responses
elicited by the wsMWNT boosted the general activity of the
host immune system and modified the progression of the
H22 tumor [52].
CNTs have also shown the potential to boost the anti-
genicity of the carried proteins or peptides. We have inves-
tigated whether MWNTs conjugated to tumor lysate protein
will enhance the efficacy of an anti-tumor immunotherapy
that employs tumor cell vaccine (TCV) in a mouse model
bearing the H22 liver cancer. The study shows that MWNTs
conjugated to tumor lysate protein enhanced the specific
anti-tumor immune response and the cancer cure rate of a
TCV immunotherapy in mice. The results suggest that
MWNTs may play a role in the development of new anti-
tumor immunotherapies [53].
The interaction of CNTs with tumor-associated macro-
phage cells deserves attention. For example, to evaluate the
potential application of CNTs for brain tumor therapy, one
group studied the uptake and toxicity of MWNTs in the
GL261 murine intracranial glioma model. It is noteworthy
that most MWNTs were uptaken by tumor-associated
macrophages. This suggests that MWNTs may potentially
be used as a novel and non-toxic vehicle for targeting
macrophages in brain tumors [54].
6 Evaluation of the risks and benefits of CNT
based materials in cancer therapies
The potential applications for CNTs in cancer therapy have
attracted increasing interest in both research and clinics.
However, debate remains over the potential risks and bene-
fits of applying CNTs in antitumor therapies. One review
article has made a comparison between the characteristics,
advantages, drawbacks, benefits, and risks associated with
these novel biocompatible forms of carbon [55]. The inter-
esting property of being taken up by various kinds of cells
without inducing severe cytotoxicity has attracted intensive
research and development interests; however, only a few

6 XU HaiYan, et al. Sci China Chem November (2010) Vol.53 No.11
examples of small molecule delivery (antibacterial, antiviral,
and anticancer agents) using f-CNTs have been reported
previously. The authors believe that this could be attributed
to the fact that only a limited portion of the whole surface is
available, and thus the drug loading does not guarantee the
desired pharmacological effect. In addition, no application
for drug delivery has yet been approved or entered the mar-
ket, which favors an increased skepticism toward any
bio-application of these nanotubes. Nevertheless, many in-
teresting results may be expected in the very near future,
which shows that CNTs need to be investigated much more
deeply for their potential impact on nanoscience. Another
article analyzes the potential, through possible toxicological
implications, of CNTs in nanomedicine. The article pro-
poses that the lack of a centralized toxicity database limits
comparison between research results and that it is necessary
to understand deeply the postexposure regeneration, resis-
tance, and mechanisms of injury in cells due to CNTs be-
fore they can be used in medicine [56].
This work was supported by the National Basic Research Program of
China (2006CB933203 & 2010CB934002).
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