scholarly journals Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1190
Author(s):  
Chitra Subramanian ◽  
Reid McCallister ◽  
Dawn Kuszynski ◽  
Mark S. Cohen
Keyword(s):  
Synergistic Effect ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Antagonistic Effect ◽  
Steroidogenic Enzymes ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Lower Toxicity

Introduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, with very poor prognosis as a majority of the patients have advanced disease at the time of diagnosis. Currently, adjuvant therapy for most patients consists of either mitotane (M) alone or in combination with multi-drug chemotherapeutics such as etoposide (E), doxorubicin (D), and cisplatin (P), known as the Italian protocol (IP; EDPM). This multi-drug treatment regimen, however, carries significant toxicity potential for patients. One way to improve toxicity profiles with these drugs in combination is to understand where their synergy occurs and over what dosing range so that lower dose regimens could be applied in combination with equal or improved efficacy. We hypothesize that a better understanding of the synergistic effects as well as the regulation of steroidogenic enzymes during combination therapy may provide more optimized combinational options with good potency and lower toxicity profiles. Methods: Two human ACC cell lines, NCI-H295R (hormonally active) and SW13 (hormonally inactive), were grown in 2D culture in appropriate growth medium. The viability of the cells after treatment with varying concentrations of the drugs (E, D, and P) either alone or in combinations with M was determined using the CellTiter Glow assay after 72 h, and the combination index for each was calculated using Compusyn by the Chou–Talalay method. The expression levels of enzymes associated with steroidogenesis were evaluated by RT-PCR in NCI-H295R. Results: When both cell lines were treated with M (ranging 25–50 μM), +E (ranging 18.75–75 μM), and +D (ranging 0.625–2.5 μM) we observed a synergistic effect (CI < 1) with potency equivalent to the full Italian protocol (IP), whereas combining M + P + D had an antagonistic effect (CI > 1) indicating the negative effect of adding cisplatin in the combination. Comparing the hormonally active and inactive cell lines, M + P + E was antagonistic in NCI-H295R and synergistic in SW13. Treatment of NCI-H295R cells with antagonistic combinations (M + P + D, M + P + E) resulted in a significant decrease in the levels of steroidogenic enzymes STAR, CYP11A1, and CYP21A2 compared to IP (p < 0.05) while M + E + D resulted in increased expression or no significant effect compared to IP across all genes tested. Conclusions: The synergistic effect for M + E + D was significant and equivalent in potency to the full IP in both cell lines and resulted in a steroidogenic gene expression profile similar to or better than that of full IP, warranting further evaluation. Future in vivo evaluation of the combination of M + E + D (with removal of P from the IP regimen) may lower toxicity while maintaining anticancer efficacy in ACC.

A novel design of wound bandage using heparin-polyvinylpyrrolidone/TiO2 nanocomposite to improved antibacterial treatment and burn wound healing effect: In vitro and in vivo evaluation

2021 ◽  
Vol 11 (11) ◽  
pp. 1808-1818
Author(s):  
Xiuli Li ◽  
Jigang Wang ◽  
Xin Li ◽  
Xiaoqian Hou ◽  
Hao Wang ◽  
...  
Keyword(s):  
Electron Microscope ◽  
Dermal Fibroblast ◽  
Synergistic Effects ◽  
Bacterial Species ◽  
Human Dermal Fibroblast ◽  
Burn Wound ◽  
In Vivo Evaluation ◽  
Closure Rate

In our current study, porous heparin-polyvinylpyrrolidone/TiO2 nanocomposite (HpPVP/TiO2) bandage were prepared via the incorporation of TiO2 into HpPVP hydrogels for biomedical applications such as burn infection. The effect of the HpPVP hydrogels and the nanoparticles of TiO2 composition on the functional group and the surface properties of the as-fabricated bandages were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometry (XRD). The presence of TiO2 nanoparticles created the internal structure of the HpPVP hydrogel that aids in a homogeneous porous structure, as indicated by the scanning electron microscope (SEM). The size distribution of the TiO2 nanoparticles was measured using a transmission electron microscope (TEM). The studies on the mechanical properties of the HpPVP hydrogel indicate that the addition of TiO2 nanoparticles increases its strength. The prepared HpPVP/TiO2 nanocomposite dressing has excellent antimicrobial activity were tested against bacterial species (Staphylococcus aureus and Escherichia coli) and has good biocompatibility against human dermal fibroblast cells (HFFF2) for biological applications. In addition, in vivo evaluations in Kunming mice exposed that the as-fabricated HpPVP/TiO2 nanocomposite bandages increased the wound curing and facilitated accelerate skin cell construction along with collagen development. The synergistic effects of the HpPVP/TiO2 nanocomposite hydrogel dressing material, such as its excellent hydrophilic nature, good bactericidal activity, biocompatibility and wound closure rate through in vivo test makes it a suitable candidate for burn infections.

CDK12 inhibition mediates DNA damage and is synergistic with sorafenib treatment in hepatocellular carcinoma

Gut ◽  
2019 ◽  
Vol 69 (4) ◽  
pp. 727-736 ◽  
Author(s):  
Cun Wang ◽  
Hui Wang ◽  
Cor Lieftink ◽  
Aimee du Chatinier ◽  
Dongmei Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Sorafenib Treatment ◽  
Hcc Cells

ObjectivesHepatocellular carcinoma (HCC) is one of the most frequent malignancies and a major leading cause of cancer-related deaths worldwide. Several therapeutic options like sorafenib and regorafenib provide only modest survival benefit to patients with HCC. This study aims to identify novel druggable candidate genes for patients with HCC.DesignA non-biased CRISPR (clustered regularly interspaced short palindromic repeats) loss-of-function genetic screen targeting all known human kinases was performed to identify vulnerabilities of HCC cells. Whole-transcriptome sequencing (RNA-Seq) and bioinformatics analyses were performed to explore the mechanisms of the action of a cyclin-dependent kinase 12 (CDK12) inhibitor in HCC cells. Multiple in vitro and in vivo assays were used to study the synergistic effects of the combination of CDK12 inhibition and sorafenib.ResultsWe identify CDK12 as critically required for most HCC cell lines. Suppression of CDK12 using short hairpin RNAs (shRNAs) or its inhibition by the covalent small molecule inhibitor THZ531 leads to robust proliferation inhibition. THZ531 preferentially suppresses the expression of DNA repair-related genes and induces strong DNA damage response in HCC cell lines. The combination of THZ531 and sorafenib shows striking synergy by inducing apoptosis or senescence in HCC cells. The synergy between THZ531 and sorafenib may derive from the notion that THZ531 impairs the adaptive responses of HCC cells induced by sorafenib treatment.ConclusionOur data highlight the potential of CDK12 as a drug target for patients with HCC. The striking synergy of THZ531 and sorafenib suggests a potential combination therapy for this difficult to treat cancer.

scholarly journals ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaonan Xi ◽  
Ning Liu ◽  
Qianqian Wang ◽  
Yahui Chu ◽  
Zheng Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Synergistic Effect ◽  
Glioma Cell ◽  
Synergistic Effects ◽  
Akt Pathway ◽  
Phase I Clinical Trials ◽  
Glioma Cell Proliferation ◽  
Pai 1

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

A Phase II Study of PXD101 in Advanced Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3583-3583 ◽  
Author(s):  
Daniel Sullivan ◽  
Seema Singhal ◽  
Michael Schuster ◽  
James Berenson ◽  
Peter Gimsing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Stable Disease ◽  
Progressive Disease ◽  
Synergistic Effects ◽  
Objective Response ◽  
Study Drug ◽  
Primary Objective

Abstract Background: PXD101 is a small molecule HDAC inhibitor of the hydroxamate class, which demonstrates broad anti-neoplastic activity in vitro and in vivo. PXD101 has antiproliferative activity on multiple myeloma cell lines, and shows additive/synergistic effects with standard agents used in myeloma, against these cell lines. PXD101 is being tested as monotherapy and in combination with standard agents for treatment of multiple myeloma. Methods: The primary objective of this study was to assess the activity of PXD101 alone or with dexamethasone, in multiple myeloma patients (pts) who have failed at least 2 prior therapies. Response was measured using the Blade criteria. PXD101 was administered as a 30-min IV infusion on Days 1–5 of a 3-wk cycle, at a dose of 1000 mg/m2/d (900 mg/m2/d in earlier patients). Patients are initially treated with PXD101 alone for two cycles. At the end of cycle two and every cycle thereafter, pts are evaluated for tumor response and continue on the study as follows: pts with objective response or stable disease continue on PXD101 monotherapy, while pts who have progressive disease (PD) are treated with a combination of PXD101 + dexamethasone (Dex). Dex was given orally 40 mg daily on Days 2–5 and 10–13 of the treatment cycle. Results: To date, 24 pts have been enrolled, 19 for which data are currently available. These pts have received a median of 5 (range 2–10) prior therapies. Seventeen pts are evaluable, 12 of whom are evaluable for ≥ 2 cycles, and 5 evaluable for 1 cycle only; 2 pts are unevaluable due to inconsistent baseline that prevented response assessment. Of the 5 pts evaluable for 1 cycle only, 4 discontinued due to PD and one withdrew from study. The 12 pts evaluable for ≥ 2 cycles received a median of 4 treatment cycles (range 2–12); 6 of these patients went on to receive PXD101+Dex. In these 12 pts, duration of PXD101 monotherapy was for 2–4 cycles, with almost all pts (10) receiving only 2 cycles. PXD101+Dex treatment in 6 pts was for 1–10 cycles (10, 6, 4, 4, 3, and 1). In 12 pts on monotherapy for ≥ 2 cycles, there were 6 SD (duration 6–12 wks) and 6 PD. The short duration of SD in PXD101 monotherapy was attributed to patient withdrawal or moving to Dex addition in spite of disease stabilization. All 6 pts receiving PXD101+Dex had previously received at least 2 Dex-containing regimens. One pt had MR (duration 6 wks), and 5 pts had SD. One pt has had SD for 35 wks, with 90% decrease in serum M-component sustained in the last 12 wks; another pt has had SD for 15 wks. In 69 cycles of treatment there were 7 Grade 3/4 adverse events assessed by the investigator as potentially related to study drug. These include anemia (2), infection, respiratory distress, hyperglycemia, thrombocytopenia, and fatigue. Conclusions: PXD101 treatment has resulted in stabilization of advanced and progressive disease, providing clinical benefit to patients. PXD101 combination with dexamethasone led to an MR as well as long duration of stable disease in patients who have previously received multiple Dex regimens. These observations support the continued exploration of PXD101 in combination with other agents for treatment of multiple myeloma.

Intracellular NAD+ Depletion Enhances Bortezomib-Induced Myeloma Cytotoxicity

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 330-330
Author(s):  
Antonia Cagnetta ◽  
Michele Cea ◽  
Chirag Acharya ◽  
Teresa Calimeri ◽  
Yu-Tzu Tai ◽  
...  
Keyword(s):  
Cell Death ◽  
Synergistic Effect ◽  
Cell Lines ◽  
Caspase 3 ◽  
Statistical Significance ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Nicotinamide Phosphoribosyltransferase

Abstract Abstract 330 Background: Our previous study demonstrated that inhibition of nicotinamide phosphoribosyltransferase (Nampt) acts by severely depleting intracellular NAD+ content and thus eliciting mitochondrial dysfunction and autophagic MM cell death. The proteasome inhibitor Bortezomib induces anti-MM activity by affecting a variety of signaling pathways. However, as with other agents, dose-limiting toxicities and the development of resistance limit its long-term utility. Here, we demonstrate that combining Nampt inhibitor and bortezomb induces synergistic anti-MM cell death both in vitro using MM cell lines or patient CD138+ MM cells and in vivo in a human plasmacytoma xenograft mouse model. Material and Methods: We utilized MM.1S, MM.1R, RPMI-8226, and U266 human MM cell lines, as well as purified tumor cells from patients relapsing after prior therapies. Cell viability and apoptosis assays were performed using Annexin V/PI staining. Intracellular NAD+ level and proteasome activity were quantified after 12, 24, and 48h exposure to single/combination drugs by specific assays. In vitro angiogenesis was assessed by Matrigel capillary-like tube structure formation assay. Immunoblot analysis was performed using antibodies to caspase-8, caspase-9, caspase-3, PARP, Bcl-2, and tubulin. CB-17 SCID male mice (n = 28; 7 mice/EA group) were subcutaneously inoculated with 5.0 × 106 MM.1S cells in 100 microliters of serum free RPMI-1640 medium. When tumors were measurable (3 weeks after MM cell injection), mice were treated for three weeks with vehicle alone, FK866 (30mg/kg 4 days weekly), Bortezomib (0.5 mg/kg twice weekly), or FK866 (30 mg/kg) plus Bortezomib (0.5 mg/kg). Statistical significance of differences observed in FK866, Bortezomib or combination-treated mice was determined using a Student t test. Isobologram analysis was performed using “CalcuSyn” software program. A combination index < 1.0 indicates synergism. Results/Discussion: Combining FK866 and Bortezomib induces synergistic anti-MM activity in vitro against MM cell lines (P<0.005, CI < 1) or patient CD138-positive MM cells (P< 0.004). FK866 plus Bortezomib-induced synergistic effect is associated with: 1)activation of caspase-8, caspase-9, caspase-3, and PARP; 2) improved intracellular NAD+ dissipation; 3) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteolytic activities; 4) inhibition of NF-kappa B signaling; and 5) inhibition of angiogenesis. Importantly, the ectopic overexpression of Nampt rescues this observed synergistic effect; conversely, Nampt knockdown by RNAi significantly enhances the anti-MM effect of bortezomib. In the murine xenograft MM model, low dose combination FK866 (30 mg/kg) and Bortezomib (0.5 mg/kg) is well tolerated, significantly inhibits tumor growth (P < 0.001), and prolongs host survival (2–2.5 months in mice receiving combined drugs, P = 0.001). These findings demonstrate that intracellular NAD+ levels represent a major determinant in the ability of bortezomib to induce apoptosis of MM cells, providing the rationale for clinical protocols evaluating FK866 together with Bortezomib to improve patient outcome in MM. Disclosures: Munshi: Celgene: Consultancy; Millenium: Consultancy; Merck: Consultancy; Onyx: Consultancy.

scholarly journals Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation

2016 ◽  
Vol 48 (5) ◽  
pp. 504-511 ◽  
Author(s):  
Fernanda Sangalli-Leite ◽  
Liliana Scorzoni ◽  
Ana Carolina Alves de Paula e Silva ◽  
Julhiany de Fátima da Silva ◽  
Haroldo Cesar de Oliveira ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
In Vivo Evaluation

scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

Induction of ferroptosis-like cell death of eosinophils exerts synergistic effects with glucocorticoids in allergic airway inflammation

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 918-927 ◽  
Author(s):  
Yanping Wu ◽  
Haixia Chen ◽  
Nanxia Xuan ◽  
Lingren Zhou ◽  
Yinfang Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Synergistic Effect ◽  
Airway Inflammation ◽  
Synergistic Effects ◽  
Morphological Characteristics ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Allergic Disorders

IntroductionEosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs).MethodsEosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation.ResultsTreatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo.ConclusionsFINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.

Chloroform Fraction of Methanolic Extract of Seeds of Annona muricata Induce S Phase Arrest and ROS Dependent Caspase Activated Mitochondria Mediated Apoptosis in Triple Negative Breast Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Ajith J. George ◽  
Bibu J. Kariyil ◽  
Usha P.T. Ayyappan ◽  
Anu Gopalakrishnan
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Triple Negative ◽  
S Phase ◽  
Chloroform Fraction ◽  
Annona Muricata ◽  
In Vivo Evaluation ◽  
Annonaceous Acetogenins

Background: Triple negative breast cancers (TNBCs) are having high morbidity and shorter survival rate in the population. These types of cancers are having high aggressiveness, lymphatic invasion and absence of receptors. The treatment options for these types of cancers are also scarce. Several studies have been conducted to investigate the effectiveness of seeds of Annona muricata for its anti cancer activities in various cancer cell lines such as lung A549, breast MCF7, colon HT-29, oral KB and human hepatoma cell lines. But works related to its anticancer effect and mechanism of action in TNBCs has not been elucidated. Objective: The present study was undertaken to evaluate the in vitro, in vivo and in silico anticancer potential of chloroform fraction of methanolic extract of seeds of Annona muricata (CMAM) against TNBC along with elucidation of its mechanistic pathway. Methods: In vitro cytotoxicity- and antiproliferative- studies in three triple negative breast cancer cell lines were conducted using MTT and SRB assays respectively. The mechanism through which CMAM exerts its pharmacological effect was elucidated in vitro employing cell morphological assessment studies using acridine orange/ ethidium bromide (AO/EB), intra cellular reactive oxygen species assay, DNA fragmentation assay, agarose gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cell cycle analysis, annexin binding assay and caspase activated mitochondria mediated apoptotic assays using western blot. In vivo evaluation in 4T1 induced murine mammary tumour model was also conducted. Phytoconstituents in CMAM was analysed using liquid chromatography mass spectroscopy. In silico binding studies with various annonaceous acetogenins against BCL-2 and cyclin E were performed. Results: Cytotoxicity studies in MDA-MD-231, 4TI and BT-549 revealed the IC50 value of CMAM to be 2.5±0.14, 4.8±0.3 and 4.5±0.16 µg/mL respectively. Anti proliferative studies in 4T1, MDA-MB-231 and BT-549 revealed the GI50 values to be 0.128+0.03, 18.03+0.20, 0.95+0.04 µg/mL respectively. CMAM exhibited its cytotoxicity through the lysis of cell membrane, ROS dependent caspase activated mitochondria mediated apoptosis, and arresting the S phase of the cell cycle. In vivo evaluation also supported the tumoricidal property of CMAM as evidenced by reduction in tumour volume and serum biomarkers. Histopathologically there was a marked reduction in cellularity, nuclear chromatin condensation and a few normal cells in group treated with CMAM at a dose of 31mg/Kg. Phytoconstituent evaluation has revealed the presence of annonaceous acetogenins in CMAM. Among the various annonaceous acetogenins, muricatacin alone showed lipophilicity and binding affinity towards BCL-2 and cyclin E1. Conclusion: The current study shows the effectiveness of CMAM against TNBC both in vitro and in vivo. This anticancerous effect of CMAM could be by virtue of its ROS dependent caspase activated mitochondria mediated apoptosis and the S-phase arrest of the cell cycle in the TNBCs. Our results indicate that the presence of annonaceous acetogenins, especially muricatacin, could be contributing to this anticanceros effect of CMAM. Thus muricatacin could be a potential candidate for the targeted therapy of TNBCs.

Preparation of Magnetic Drug Loaded Nanoparticles and Its Anticancer Efficacy Against Nasopharyngeal Carcinoma Cells

2021 ◽  
Vol 13 (5) ◽  
pp. 857-863
Author(s):  
Jingjing Chen ◽  
Cheng Kang
Keyword(s):  
Magnetic Nanoparticles ◽  
Nasopharyngeal Carcinoma ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Anticancer Efficacy ◽  
Normal Tissues ◽  
Chemotherapy Agent

As an important drug for the treatment of cancer, cis-diamine dichloroplatinum (CDDP) has poor solubility and antagonistic effect when it is used as a chemotherapy agent alone, leading to the insufficient dose in actual administration. In order to solve the above problems, increase the targeting property of CDDP carrier and prolong the half-life period of CDDP’s sustained-release, it is necessary to design a magnetic nano-carrier for CDDP with magnetic targeting function to reduce the damage of CDDP to normal tissues in vivo and improve the therapeutic effect of cancer. Carboxymethyl chitosan (CMCS) is used to directly coat oleic acid (OA)-modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) to create the nano-scale CMCS magnetic nanoparticles (CMCS/OA-Fe2O3 NPs), and CDDP loaded magnetic nanoparticles (CMCS/OA-Fe2O3 NPs/CDDP) are prepared by the bonding interaction between carboxyl groups on the surface of CMCS and the anticancer drug CDDP. The magnetic drug loaded nanoparticles are characterized, and the results show that the magnetic nanoparticles are successfully embedded in CMCS and loaded with CDDP, with the drug load of 43.65 ± 2.37%. MTT assay, flow cytometry and invasion assay are applied to evaluate the inhibitory effect of magnetic drug loaded nanoparticles to nasopharyngeal carcinoma (NPC) cells HNE-1. The results suggest that the magnetic drug loaded nanoparticles successfully prepared have significant inhibitory effect on HNE-1 cells in vitro. Therefore, the magnetic drug loaded nanoparticles prepared have a good therapeutic effect on NPC.

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