Apoptosis of Cancer Cells Induced by HAP Nanoparticles

To confirm apoptosis is one of the hepatoma cells death pathways after HAP nanoparticles absorption,hepatoma cells were collected for ultrathin sections preparation and examined under a transmission electron microscope（TEM）after 1 h incubation with HAP nanoparticle.Apoptosis was detected by TUNEL technique.After absorption.some vacuoles with membrane containing HAP nanoparticles were found in cytoplasma.The nuclear enrelope shrinked.and some area pullulated from nucleus.The karyotin became pycnosis and assembled at the edge.An apoptosis body was found.and the data of IOD and numbers of the positive apoptosic signals in nuclear area of slides could illustrate much more apoptosis in the HAP group than those in the control group（P〈0.001）.The experimental results indicate that the HAP nanoparticles can induce cancer cells apoptosis.

Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-L-lysine-Assisted Magnetic Iron Oxide Nanoparticles

Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.

Electrochemical study of the effect of functionalized nickel nanoparticles on cellular uptake of leukemia cancer cells in vitro

In this study, we have fabricated the functionalized nickel nanoparticles and investigated their effects on cellular uptake of quercetin in leukemia K562 cancer cells by using electrochemical assay. The results indicate that nickel nanoparticles could efficiently enhance the quercetin uptake and increase the intracellular accumulation in cancer cells, implying the great potential of functionalized nickel nanoparticles in target cancer therapy.

Gold Nanoparticles: Synthesis and Effect on Viability of Human Non-Small Lung Cancer Cells

Gold nanoparticles recently showed great interest for many uses including food, drug and medical applications. The algae Undaria sp. well known as wakame in South Asia are considered to be large edible brown algae. It provides nutritious source of dietary fiber, vitamin Bs and mineral. The present study aimed to investigate the use of Undaria sp. for green synthesis of metallic gold nanoparticles. The synthesized nanoparticles were characterized for physicochemical properties including size measurement and tested in vitro for their effect on viability of human non-small lung cancer H-460 cell line using the MTT assay. From the results, brown algae were able to chemically form nanoparticles with chloroauric acid solution possibly due to the sulphated polysaccharides found in algae. The particle sizes were found to be approximately 10 nm. The gold nanoparticles stabilized by the algae could decrease the cancer cell viability. However, the properties and biological activity of nanoparticles seemed to depend upon reaction time and temperature. Conclusively, gold nanoparticles synthesized and stabilized by the algae could decrease the cancer cell viability, thus indicating the potential of such nanoparticles for further study for anticancer activity.

Ultrastructure Changes and Mechanism of Cancer Cells Induced by Inorganic Crystal Nanoparticles

The purpose of this study was to examine the changes of cancer cell in ultrastructure after inorganic crystal nanoparticles （ICN） absorption. HAP and TiO2 nanoparticles were incubated with the Bet- 7402 cells for 1 h and 8 h respectively. Then, cancer cells were collected and examined under transmission electron microscope （TEM）. In cytoplasm, nanoparticle were contained in some vacuoles. Some death features of cell appear. The experimental results indicated that ICN can induce cancer cells death.

Curcumin gum Arabic nanoparticles demonstrate potent antioxidant and cytotoxic properties in human cancer cells

The main purpose of the study was to enhance the stability and therapeutic effects of Curcumin(Cur)through nanoformulation with gum Arabic(GA)as a coating agent through an efficient synthetic approach.The antioxidant properties of the developed nanoparticles(Cur/GANPs)were assessed through several in vitro assays,such asβ-carotene bleaching activity,DPPH,and nitric oxide scavenging activities in addition to evaluating its inhibitory activity on angiotensinconverting enzyme(ACE).The cytotoxicity of Cur/GANPs was evaluated in vitro using different types of human cancer cells including breast cancer(MCF7,MDA-MB231),liver cancer(HepG2),and colon cancer(HT29)cells.The prepared particles displayed an elliptical shape with a size ranging between 20–260 nm and a potential difference of–15 mV.The Cur/GANPs exhibited significant antioxidant activity compared to free curcumin when using concentrations between 31.5 and 500μg/mL.The Cur/GANPs also had inhibited the growth of all cancer cell lines in a proportional trend with concentrations used.Hence,the encapsulation with gum Arabic has augmented the antioxidant and anti-neoplastic effects of Curcumin.Therefore,Cur/GANPs may have effective therapeutic properties in diseases attributed to oxidative stress like cancer and hypertension.

Change in Shape and Crystal Structure of HAP Nanoparticles during Absorption into Cell

The change of hydroxyapatite （HAP） nanoparticles in shape and crystal structure after endocytosis into cancer cells was studied. BEL7402 cells were incubated with HAP nanoparticles for 2 hour, 8 hours, 20 hours, respectively. Then, the cells were collected and viewed under a transmission electronic microscope （TEM）. Electronic diffraction （ED） attached to TEM was used to detect the properties of the particles. The results show that HAP particles in the cytoplasm can be degraded in cytoplasm. The degradation process is prolonged by more than 20 hours. Thus, it is concluded that HAP nanoparticles would be degraded after kill cells or delivery gene.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

Selective inhibition of Hepatocarcinoma cells by apatite nanoparticles

The effects of HAP nanoparticles on growth of primary normal animal liver cells and on growth of hepatocarcinoma cell line Bel 7402 in vitro were studied respectively and were compared with each other.The results showed that HAP nanoparticles in certain concentration inhibited growth of cancer cells significantly while did not inhibite normal cells in the same concentration.The inhibition ratio was as high as very high dosage of adriamycin.It was concluded that HAP nanoparticles can selectively inhibited cancer cells.

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.

Effect and molecular mechanism of mir-146a on proliferation of lung cancer cells by targeting and regulating MIF gene

Objective: To discuss the effect and molecular mechanism of mi R-146 a on the proliferation of lung cancer cells by targeting and regulating the macrophage migration inhibitory factor(MIF) gene. Methods: RT-PCR was employed to detect expression of mi R-146a; immunohistochemistry was used to detect the expression of MIF. The luciferase reporter gene technique was adopted to verify that MIF was the specific reverse target gene of mi R-146 a and the liposome LipofectamineTM2000 was employed to transfer the modeled mi R-146 a mimics, and mi R-146 a negative control(NC) in NSCLC cells to detect the expression of MIF m RNA and protein. MTT assay was used to detect cell viability, cloning technique to detect cell proliferation ability, Annexin V-PI to detect cell apoptosis, UV spectrophotometry to detect viability of cysteinyl aspartate specific proteinase 3(Caspase 3), and western blot to detect expression of nuclear factor-κB(NF-κB) in cells. Results: The expression of mi R-146 a in NSCLC lung tissues was lower than that in the normal lung tissues besides the lung cancer; while the expression of mi R-146 a in NSCLC cells was lower than that in normal human embryonic lung tissues. It was chosen as the subsequent cell line for its appropriate expression in A549. The expression of MIF protein in NSCLC lung tissues was higher than that in the normal lung tissues besides the lung cancer. The luciferase reporter gene proved that MIF was the reverse target gene of mi R-146 a. The mi R-146 a mimics were transfected into A549 cells through the liposome. Compared with NC group, the expression of MIF protein and m RNA was significantly decreased(P<0.01), with the decrease in the cell viability(P<0.01), the decrease in the number of clones(P<0.01), cell apoptosis(P<0.01), the increase in the activity of Caspase 3(P<0.01), and decrease in the phosphorylation of NF-κB p65(P<0.01). Conclusions: mi R-146 a has low expression in NSCLC tissues and cell lines, while MIF has the over expression in NSCLC tissues. The increased expression of mi R-146 a can inhibit the expression of MIF via the gene targeting and thus inhibit the proliferation of A549 cells and induce the apoptosis of cancer cells, which may be realized through NF-κB signaling pathway.

Roscovitine synergizes with conventional chemo-therapeutic drugs to induce efficient apoptosis of human colorectal cancer cells

AIM: To examine the ability of cyclin-dependent kinase inhibitor (CDKI) roscovitine (Rosco) to enhance the antitumor effects of conventional chemotherapeutic agents acting by different mechanisms against human colorectal cancer. METHODS: Human colorectal cancer cells were treat-ed, individually and in combination, with Rosco, taxol, 5-Fluorouracil (5-FU), doxorubicine or vinblastine. The antiproliferative effects and the type of interaction of Rosco with tested chemotherapeutic drugs were de-termined. Cell cycle alterations were investigated by fluorescence-activated cell sorter FACS analysis. Apop-tosis was determined by DNA fragmentation assay. RESULTS: Rosco inhibited the proliferation of tumor cells in a time-and dose-dependent manner. The ef-ficacies of all tested chemotherapeutic drugs were markedly enhanced 3.0-8.42 × 103 and 130-5.28 × 103 fold in combination with 5 and 10 μg/mL Rosco, re-spectively. The combination of Rosco and chemothera-peutic drugs inhibited the growth of human colorectal cancer cells in an additive or synergistic fashion, and in a time and dose dependent manner. Rosco induced apoptosis and synergized with tested chemothera-peutic drugs to induce efficient apoptosis in human colorectal cancer cells. Sequential, inverted sequential and simultaneous treatment of cancer cells with combi-nations of chemotherapeutic drugs and Rosco arrested the growth of human colorectal cancer cells at various phases of the cell cycle as follows: Taxol/Rosco (G2/M-and S-phases), 5-FU/Rosco (S-phase), Dox/Rosco (S-phase) and Vinb/Rosco (G2/M-and S-phases). CONCLUSION: Since the eff icacy of many anticancer drugs depends on their ability to induce apoptotic cell death, modulation of this parameter by cell cycle inhibi-tors may provide a novel chemo-preventive and chemo-therapeutic strategy for human colorectal cancer.

Charcoal Nanoparticles as a Delivery System for Doxorubicin and Sorafenib in Treatment of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.

Engineering polymer nanoparticles using cell membrane coating technology and their application in cancer treatments:Opportunities and challenges

Nanotechnology has revolutionized cancer drug delivery,and recent research continues to focus on the development of“one-size-fits-all,”i.e.,“all-in-one”delivery nanovehicles.Although nanomedicines can address significant shortcomings of conventional therapy,biological barriers remain a challenge in their delivery and accumulation at diseased sites.To achieve long circulation time,immune evasion,and targeted accumulation,conventional nanocarriers need modifications,e.g.,PEGylation,peptide/aptamer attachment,etc.One such modification is a biomimetic coating using cell membrane(CM),which can offer long circulation or targeting,or both.This top-down CM coating process is facile and can provide some advantageous features over surface modification by synthetic polymers.Herein,an overview is provided on the engineering of CM camouflaged polymer nanoparticles.A short section on CM and the development of CM coating technology has been provided.Detailed description of the preparation and characterization of CM camouflaged polymer NPs and their applications in cancer treatment has been reported.A brief comparison between CM coating and PEGylation has been highlighted.Various targeting approaches to achieve tumor-specific delivery of CM coated NPs have been summarized here.Overall,this review will give the readers a nice picture of CM coated polymer NPs,along with their opportunities and challenges.

Using the Electromagnetics of Cancer’s Centrosome Clusters to Attract Therapeutic Nanoparticles

This paper summarizes recent research findings concerning centrioles, centriole duplication, centriole overduplication, supernumerary centrioles, centrosomes, and centrosome amplification. The paper then discusses the status of ongoing research on the use of nanoparticles for cancer treatment. The research findings show that a centriole produces an electromagnetic field apparently due to the longitudinal oscillation of its microtubules (MTs). A cluster of centrioles is therefore presumed to produce an enhanced electromagnetic field. Individual centrioles are immersed in a cloud of electron-dense material (proteins) which together with the centrioles is known as the centrosome. A cluster of centrioles thus produces a cluster of centrosomes—a hallmark of cancer cells. With enhanced electromagnetic fields, centrosome clusters provide an attraction for magnetically charged nanoparticles. These nanoparticles however are not attracted to normal cells which with only two (or at most four) centrioles, have a weaker magnetic field. The idea is simple: Magnetized and therapeutic nanoparticles are directed toward tumors and then attracted to the centrosome clusters of the tumor cells. Once inside the tumor cells, the nanoparticles can release their toxins.

Selenium nanoparticles enhance the chemotherapeutic efficacy of pemetrexed against non-small cell lung cancer

Selenium(Se)plays an important role in the development and treatment of lung cancer,yet its specific mechanisms remain elusive.Lower Se level in serum was noted in lung cancer patients compared to normal controls.Therefore,developing effective therapeutic adjuvants containing Se might benefit the treatment of lung cancer patients.This study aimed to investigate the association between Se and the chemotherapeutic efficacy of lung cancer.Lentinan-modified selenium nanoparticles(LET-Se NPs)were created to develop and verify the effectiveness of Se containing adjuvant applied with pemetrexed on lung cancer cells.A synergistic effect was observed between LET-Se NPs and pemetrexed in vitro.The combination of LET-Se NPs and pemetrexed could induce reactive oxygen species overproduction,mitochondrial dysfunction and DNA damage,ultimately leading to cancer cell apoptosis.It is implied that LET-Se NPs might be a promising sensitizer to pemetrexed chemotherapy and could potentially enhance chemotherapy efficiency in non-small cell lung cancer.

Black phosphorous nanosheets−gold nanoparticles−cisplatin for photothermal/photodynamic treatment of oral squamous cell carcinoma

To improve five-year survival rate of oral squamous cell carcinoma(OSCC),the development of a novel composite material of black phosphorus nanosheets(BPNSs)and gold nanoparticles(AuNPs)for tumor treatment was carried out.The purpose of this study is to evaluate the cytostatic effects of BPNSs,AuNPs loaded with cisplatin(CDDP)on human tongue squamous cell carcinoma cells lines(SCC-9),and 7,12-dimethylbenz anthracene induced cheek squamous cell carcinoma was validated in golden hamsters animal models.The results showed that BPNSs could efficiently inhibit the metastasis and growth of OSCC compared with CDDP and AuNPs.And a combination composite of AuNPs−BPNSs loaded with CDDP could more effectively inhibit the metastasis and growth of OSCC,which might be due to the high drug-loading capacity,excellent photothermal properties and the combination of photodynamic and photothermal therapy of BPNSs and AuNPs,as well as the synergistic effects of AuNPs,BPNSs and CDDP.

Recent Advances of Persistent Luminescence Nanoparticles in Bioapplications

Persistent luminescence phosphors are a novel group of promising luminescent materials with afterglow properties after the stoppage of excitation.In the past decade,persistent luminescence nanoparticles(PLNPs)with intriguing optical properties have attracted a wide range of attention in various areas.Especially in recent years,the development and applications in biomedical fields have been widely explored.Owing to the efficient elimination of the autofluorescence interferences from biotissues and the ultra-long near-infrared afterglow emission,many researches have focused on the manipulation of PLNPs in biosensing,cell tracking,bioimaging and cancer therapy.These achievements stimulated the growing interest in designing new types of PLNPs with desired superior characteristics and multiple functions.In this review,we summarize the works on synthesis methods,bioapplications,biomembrane modification and biosafety of PLNPs and highlight the recent advances in biosensing,imaging and imaging-guided therapy.We further discuss the new types of PLNPs as a newly emerged class of functional biomaterials for multiple applications.Finally,the remaining problems and challenges are discussed with suggestions and prospects for potential future directions in the biomedical applications.

Inhibition of Wnt signaling by Frizzled7 antibody-coated nanoshells sensitizes triple-negative breast cancer cells to the autophagy regulator chloroquine

Nano Research volume 13,pages1693–1703(2020)Cite this article 137 Accesses 6 Altmetric Metrics details Abstract Despite improvements in our understanding of the biology behind triple-negative breast cancer(TNBC),it remains a devastating disease due to lack of an effective targeted therapy.Inhibiting Wnt signaling is a promising strategy to combat TNBC because Wnt signaling drives TNBC progression,chemoresistance,and stemness.However,Wnt inhibition can lead to upregulation of autophagy,which confers therapeutic resistance.This provides an opportunity for combination therapy,as autophagy inhibitors applied concurrently with Wnt inhibitors could increase treatment efficacy.Here,we applied the autophagy inhibitor chloroquine(CQ)to TNBC cells in combination with Frizzled7 antibody-coated nanoshells(FZD7-NS)that suppress Wnt signaling by blocking Wnt ligand/FZD7 receptor interactions,and evaluated this dual treatment in vitro.We found that FZD7-NS can inhibit Axin2 and CyclinD1,two targets of canonical Wnt signaling,and increase the expression of LC3,an autophagy marker.When FZD7-NS and CQ are applied together,they reduce the expression of several stemness genes in TNBC cells,leading to inhibition of TNBC cell migration and self-renewal.Notably,co-delivery of FZD7-NS and CQ is more effective than either therapy alone or the combination of CQ with free FZD7 antibodies.This demonstrates that the nanocarrier design is important to its therapeutic utility.Overall,these findings indicate that combined regulation of Wnt signaling and autophagy by FZD7-NS and CQ is a promising strategy to combat TNBC.

Near infrared light triggered nitric oxide releasing platform based on upconversion nanoparticles for synergistic therapy of cancer stem-like cells

Near infrared(NIR) light-driven nitric oxide(NO) release nano-platform based on upconversion nanoparticles(UCNPs) and light sensitive NO precursor Roussin's black salt(RBS) was fabricated to generate NO upon 808 nm irradiation. The application of 808 nm laser as the excitation source could achieve better penetration depth and avoid overheating problem. The combination of UCNPs and RBS could realize the on-demand release of NO at desired time and location by simply controlling the output of NIR laser.Cellular uptake results showed that more nanoparticles were internalized in cancer stem-like cells(CSCs)rather than non-CSCs. Therefore, a synergistic cancer therapy strategy to eradicate both CSCs and nonCSCs simultaneously was developed. Traditional chemo-drug could inhibit non-CSCs but has low killing efficiency in CSCs. However, we found that the combination of NO and chemotherapy could efficiently inhibit CSCs in bulk cells, including inhibiting mammosphere formation ability, decreasing CD44^+/CD24^- subpopulation and reducing tumorigenic ability. The mechanism studies confirmed that NO could not only induce apoptosis but also increase drug sensitivity by declining drug efflux in CSCs. This UCNPsbased platform may provide a new combinatorial strategy of NO and chemotherapy to improve cancer treatment.