Carbon dot-based nanomaterials: a promising future nano-platform for targeting tumor-associated macrophages.

The tumor microenvironment (TME) is the internal environment that tumors depend on for survival and development. Tumor-associated macrophages (TAMs), as an important part of the tumor microenvironment, which plays a crucial role in the occurrence, development, invasion and metastasis of various malignant tumors and has immunosuppressant ability. With the development of immunotherapy, eradicating cancer cells by activating the innate immune system has yielded encouraging results, however only a minority of patients show a lasting response. Therefore, in vivo imaging of dynamic TAMs is crucial in patient-tailored immunotherapy to identify patients who will benefit from immunotherapy, monitor efficacy after treatment, and identify alternative strategies for non-responders. Meanwhile, developing nanomedicines based on TAMs-related antitumor mechanisms to effectively inhibit tumor growth is expected to become a promising research field. Carbon dots (CDs), as an emerging member of the carbon material family, exhibit unexpected superiority in fluorescence imaging/sensing, such as near infrared imaging, photostability, biocompatibility and low toxicity. Their characteristics naturally integrate therapy and diagnosis, and when CDs are combined with targeted chemical/genetic/photodynamic/photothermal therapeutic moieties, they are good candidates for targeting TAMs. We concentrate our discussion on the current learn of TAMs and describe recent examples of macrophage modulation based on carbon dot-associated nanoparticles, emphasizing the advantages of their multifunctional platform and their potential for TAMs theranostics.

MiRNA-520a-3p combined with folic acid conjugated Fe2O3@PDA multifunctional nanoagents for MR imagine and antitumor gene-photothermal therapy.

Osteosarcoma (OS) is a primary malignant bone tumor that occurs mainly in adolescents. Researchers are devoting to develop combination therapy methods in a multifunctional nanoplatform for the treatment of osteosarcoma. The results of previous research have shown that up-regulation of miR-520a-3p could induce anticancer effects in osteosarcoma. In order to improve the effect of gene therapy (GT), we attempted to carry miR-520a-3p in a multifunctional vector for comprehensive therapy. Fe2O3is a type of magnetic resonance imaging (MRI) contrast that is widely used as a drug delivery agent. When coated with polydopamine (PDA), it can also be used as a photothermal therapy (PTT) agent (Fe2O3@ PDA). To deliver nanoagents targeted to a tumor site, folic acid (FA) conjugated with Fe2O3@PDA was manufactured as FA-Fe2O3@PDA. FA was chosen as the target molecule to enhance utilization and reduce toxicity of nanoparticles. However, the therapeutic efficacy of FA-Fe2O3-PDA combined with miR-520a-3p has not yet been studied. In this study, we synthesized FA-Fe2O3@PDA-miRNA and investigated the potential of combining PDA regulated PTT and miR-520a-3p regulated GT to kill osteosarcoma cells. The results indicated that down-regulation of interleukin 6 receptor (IL6R) by miR-520a-3p and the photothermal ability of PDA could induce satisfactory anticancer effects in osteosarcoma, and the curative ratio was better than that used alone PTT or GT. Moreover, as a kind ofT2magnetic contrast, miRNA-Fe2O3@PDA-FA can be used for MRI. These findings indicated that miRNA-Fe2O3@PDA-FA is an effective anti-tumor nanovector for PTT combined with GT.

The clinical value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) semi-quantitative parameters in monitoring neoadjuvant chemotherapy response of osteosarcoma.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive technique which could monitor tumor morphology, blood vessel dynamics, and micro-environmental changes. PURPOSE: To evaluate the value of DCE-MRI semi-quantitative parameters in monitoring the neoadjuvant chemotherapy (NAC) response of osteosarcoma. MATERIAL AND METHODS: Twenty-five patients pathologically confirmed as osteosarcoma received four cycles of NAC followed by surgery. All patients underwent conventional and dynamic MRI twice, before starting chemotherapy and before surgical treatment. With a reference standard of histological response (tumor necrosis rate), semi-quantitative parameters were compared between good response group (TNR ≥ 90%) and non-response group (TNR < 90%). The differences between intra- and inter-group parameters before and after NAC were analyzed by Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was generated to assess the parameters' efficacy in predicting the outcome of NAC. RESULTS: The changes were statistically significant on slope, maximum signal intensity (SImax), time to peak (TTP), signal enhanced extent (SEE), peak percent enhancement (PPE), washout rate (WOR), and enhancement rate (ER) in the good response group (P < 0.05), while only SImax and SEE were different in the non-response group after NAC. The changes in Slope, SImax, TTP, SEE, WOR, and ER were markedly different (P < 0.05) between the two groups after NAC. Also, at the threshold values of 3.2%/s, 175 s, and 5.4% (slope, TTP, and ER), the sensitivity and specificity for predicting good response to chemotherapy were 83.3% and 92.3%, 91.7% and 69.2%, 84.6% and 75.0%, respectively. CONCLUSION: Slope, TTP, and ER values could be used to evaluate and predict the response to NAC in osteosarcoma.

LINC01116 Promotes Doxorubicin Resistance in Osteosarcoma by Epigenetically Silencing miR-424-5p and Inducing Epithelial-Mesenchymal Transition.

Background: Development of resistance to doxorubicin-based chemotherapy limits its curative effect in osteosarcoma. In the current study, we focused on investigating the mechanisms underlying the development of doxorubicin resistance in osteosarcoma. Methods: The human osteosarcoma cell line MG-63 and doxorubicin-resistant MG-63/Dox cells were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the long non-coding RNA LINC01116 in the two cell lines. Then, the specific shRNA for LINC01116 was employed to suppress LINC01116 expression in MG-63/Dox cells. Cell viability was assessed by the CCK-8 and colony formation assays. Cell migration and invasion were evaluated by the transwell assay. Moreover, the epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin, vimentin, and N-cadherin were evaluated by Western blotting. The regulation of LINC01116 on miR-424-5p expression was examined using methylation-specific PCR, RNA immunoprecipitation, and Western blotting assay. The potential targeting of HMGA2 by miR-424-5p was predicted using the bioinformatics databases TargetScan and miRanda and verified by a dual-luciferase reporter assay. Results: LINC01116 was more highly expressed in MG-63/Dox cells than in MG-63 cells. Inhibition of LINC01116 suppressed cell viability, migration, and invasion, along with upregulating the expression of E-cadherin, downregulating vimentin, and attenuating doxorubicin resistance in MG-63/Dox cells. Further mechanism-related investigations indicated that LINC01116 regulated HMGA2 expression via the EZH2-associated silencing of miR-424-5p. Conclusion: LINC01116 exerts regulatory effects on doxorubicin resistance through the miR-424-5p axis, providing a potential approach to overcoming chemoresistance in osteosarcoma.

Microfluidic chip enabled one-step synthesis of biofunctionalized CuInS2/ZnS quantum dots.

Biofunctionalized quantum dots (QDs) are effective target fluorescent labels for bioimaging. However, conventional synthesis of biofunctionalized I-III-VI core-shell CuInS2/ZnS QDs requires complex bench-top operations, resulting in limited product performance and variety, and is not amenable to a 'one-step' approach. In this work, we have successfully demonstrated a fully automated method for preparing denatured bovine serum albumin (dBSA)-CuInS2/ZnS QDs by introducing microfluidic (MF) chips to synthesize biofunctionalized QDs, hence establishing a 'one-step' procedure. We have also studied and optimized the reaction synthesis parameters. The emission wavelength of the dBSA-CuInS2/ZnS QDs is located in the near-infrared range and can be tuned from 650 to 750 nm by simply varying the reaction parameters. In addition, the 'one-step'-synthesized dBSA-CuInS2/ZnS QDs have a long average fluorescence lifetime of 153.76 ns and a small particle size of 5 ± 2 nm. To demonstrate the applicability of the 'one-step'-synthesized dBSA-CuInS2/ZnS QDs in bioimaging studies, we modified the QDs with folic acid and hyaluronic acid, and then performed target bioimaging and cytotoxicity tests on macrophages, liver cancer cells and pancreatic cancer cells. The cell images show that the red emission signals originate from the QDs, which indicates that the dBSA-CuInS2/ZnS QDs prepared by the MF approach are suitable optical contrast agents for target bioimaging. This 'one-step' MF-based QD synthesis approach could serve as a rapid, cost-effective, and small-scale nanocrystal production platform for complex QD formulations for a wide range of bioapplications.

LncRNA MEG3 suppressed the progression of ovarian cancer via sponging miR-30e-3p and regulating LAMA4 expression.

BACKGROUND: Ovarian cancer (OC) is a common female reproductive malignancy with a high mortality rate. Although LAMA4 was observed to be downregulated in OC cells, its mechanism in regulating OC metastasis is still unknown. This study aimed to investigate the effect of LAMA4 and its mechanism on OC. METHODS: To achieve this aim, a microarray analysis was performed to screen out the key genes involved in OC pathogenesis. Western-blot and qRT-PCR assays were also carried out to detect protein and mRNA expressions, respectively. A luciferase reporter assay was further used to confirm the direct interaction of miR-30e-3p with MEG3, and the direct interaction of miR-30e-3p with LAMA4 mRNA. Cytological experiments (CCK8, colony formation assay, wound-healing assay etc.) were then performed to explore the roles of miR-30e-3p, MEG3, and LAMA4 in OC cells. RESULTS: After carrying out microarray analysis, LAMA4 was confirmed as a key gene associated with OC pathogenesis. Research results proved that miR-30e-3p was markedly upregulated, while MEG3 and LAMA4 were noticeably downregulated in OC tissues and cells. The overexpression of LAMA4 significantly impaired the proliferation, migration, and invasion of OC cells. However, the upregulation of MEG3 increased the expression of LAMA4 by sponging miR-30e-3p, which alleviated the malignancy of OC cells. CONCLUSIONS: Observations showed that forced LAMA4 overexpression could inhibit OC progression, which was regulated by MEG3 via sponging miR-30e-3p. The findings of this research could provide new insights into the mechanism by which MEG3 and LAMA4 exert their anti-oncogenic roles in OC progression.Trial registration Not applicable.

The lncRNA SNHG3 accelerates papillary thyroid carcinoma progression via the miR-214-3p/PSMD10 axis.

Small nucleolar RNA host gene 3 (SNHG3) is a long noncoding RNA (lncRNA), which is known to promote oncogenesis in many cancers but its role in human papillary thyroid carcinoma (PTC) remains poorly understood. We therefore assessed SNHG3 expression in PTC tissues via quantitative reverse transcription polymerase chain reaction. We additionally knocked down SNHG3 in PTC cells using short-hairpin RNAs (shRNAs) to explore its functional roles in PTC. The ability of SNHG3 to bind to specific microRNAs (miRNAs) was predicted using a bioinformatics tool, and this binding was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. We then used a tumor xenograft model to assess the relevance of SNHG3 in vivo. We determined SNHG3 expression to be elevated in PTC tissues relative to controls, with advanced tumor-node-metastasis stage and lymph node metastasis being associated with this expression. Knocking down SNHG3 significantly reduced in vitro PTC cell migration, invasion, proliferation, and colony formation, and it further slowed the growth of tumors in vivo. We found that SNHG3 could bind to miR-214-3p as a competing endogenous RNA (ceRNA) for this miRNA, thereby regulating proteasome 26S subunit non-ATPase 10 (PSMD10) expression, a miR-214-3p target. These results thus indicate that SNHG3 is an oncogenic lncRNA in PTC, acting at least in part via the miR-214-3p/PSMD10 axis.

LINC01116 targets miR-520a-3p and affects IL6R to promote the proliferation and migration of osteosarcoma cells through the Jak-stat signaling pathway.

OBJECTIVE: The purpose of this study was to find out the important lncRNA-miRNA-mRNA axis and pathway in osteosarcoma (OS) through bioinformatics analysis and verify the biological functions of lncRNA/miRNA/mRNA in OS through in vitro and in vivo assays. METHODS: The differential expression mRNAs and lncRNAs were identified through microarray analysis, and the altered pathways were identified by GSEA. The Pearson Coefficient was used to analyze the correlations between mRNAs and lncRNAs. Kaplan-Meier survival analysis was preformed using patient information in GEO database. Their target miRNAs were predicted by Targetscan and miRanda database and confirmed by dual luciferase reporter assay. QRT-PCR were utilized to detected the relative expressions of mRNAs, miRNAs and lncRNAs. The expressions of IL6R protein and pathway related proteins were detected by western blot. OS cell viability, migration and apoptosis were determined through MTT assay, Transwell assay and flow cytometry. Tumor formation in nude mice verified the influence of LINC01116 in vivo. RESULTS: The Jak-stat signaling pathway was activated in OS tissues. LINC01116 expression was positively correlated with IL6R expression. MiR-520a-3p targeted the 3'-UTR of LINC01116 and IL6R. Lower expression levels of miR-520a-3p significantly correlated with shorter survival of patients. LINC01116 and IL6R were up-regulated while miR-520a-3p was down-regulated in OS. LINC01116 and IL6R promoted the viability and migration of OS cells, while miR-520a-3p acted as a tumor suppressor. MiR-520a-3p inhibitor could rescue the suppressive effects of si-LINC011116 and si-IL6R on OS development. The Jak-stat signaling pathway related proteins were also down-regulated by miR-520a-3p. Down-regulation of LINC01116 inhibited the tumor growth in nude mice. CONCLUSION: LINC01116 up-regulated IL6R in OS through targeting miR-520a-3p, thus activating the Jak-stat signaling pathway and promoting the progression of OS.

Intracerebral schwannoma: A case report and literature review.

Intracranial schwannoma accounts for between 5 and 8% of intracranial tumors, whereas intracerebral schwannoma, a rare disease, accounts for <1% of intracranial schwannomas. In addition to the present case report, a total of 84 cases reported within China and elsewhere were reviewed and summarized, and the age of the tumor onset, the site of disease, imaging results, clinical presentation, pathological classification and prognosis were analyzed. The present case report described a 12-year-old female with an intracerebral schwannoma in the brainstem, who was followed-up for 5 years using magnetic resonance imaging after a surgical resection without recurrence, and clinical symptoms were reported to have completely resolved. The incidence of intracerebral schwannoma was low among cases, and the correct diagnosis was not able to be made preoperatively, and the majority of cases were diagnosed on the basis of postoperative pathology. The majority of cases analyzed were supratentorial, occurring at an age ≤40 according to previous literature. In addition, 33% of patients presented with subtentorial schwannoma, occurring at an age >40. The prognosis was classified as good (patient can live independently) for the majority of patients if surgery was able to completely resect the lesion.

miR-141 promotes colon cancer cell proliferation by inhibiting MAP2K4.

MicroRNAs (miRNAs or miRs) can function as tumor-suppressor or oncogenic genes. Upregulation of miRNA-141 has been frequently observed in colorectal cancer (CRC) samples. The experimentally observed targets of miR-141 include the tumor-suppressor gene mitogen-activated protein kinase kinase 4 (MAP2K4). The aim of the present study was to investigate the role of miR-141 in the proliferation of colonic cancer. Western blotting, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression levels of miR-141 and MAP2K4 in colonic adenocarcinoma (CAC) and adjacent non-cancerous (NC) tissue samples, as well as in human CAC cell lines (HT29, T94 and LS174). MTT assay was used to investigate the proliferation and apoptosis of these three cell lines. The expression levels of miR-141 were significantly upregulated in clinical samples of CAC, compared with adjacent NC tissues. By contrast, MAP2K4 was downregulated in CAC. The in vitro assays demonstrated that overexpression of miR-141 resulted in cell proliferation of CAC by inhibiting MAP2K4 activity. Our study suggests that targeting the miR-141-MAP2K4 signaling pathway may represent a novel approach for the treatment of CRC.

New Generation Cadmium-Free Quantum Dots for Biophotonics and Nanomedicine.

This review summarizes recent progress in the design and applications of cadmium-free quantum dots (Cd-free QDs), with an emphasis on their role in biophotonics and nanomedicine. We first present the features of Cd-free QDs and describe the physics and emergent optical properties of various types of Cd-free QDs whose applications are discussed in subsequent sections. Selected specific QD systems are introduced, followed by the preparation of these Cd-free QDs in a form useful for biological applications, including recent advances in achieving high photoluminescence quantum yield (PL QY) and tunability of emission color. Next, we summarize biophotonic applications of Cd-free QDs in optical imaging, photoacoustic imaging, sensing, optical tracking, and photothermal therapy. Research advances in the use of Cd-free QDs for nanomedicine applications are discussed, including drug/gene delivery, protein/peptide delivery, image-guided surgery, diagnostics, and medical devices. The review then considers the pharmacokinetics and biodistribution of Cd-free QDs and summarizes current studies on the in vitro and in vivo toxicity of Cd-free QDs. Finally, we provide perspectives on the overall current status, challenges, and future directions in this field.

Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line.

First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro transfection results from BCPV-siRNA, a newly developed biodegradable transfection agent, BCPV, is being probed for transfection performance in an animal model.

Diffusion-weighted magnetic resonance imaging without bowel preparation for detection of ulcerative colitis.

AIM: To evaluate the accuracy of diffusion-weighted imaging (DWI) without bowel preparation, the optimal b value and the changes in apparent diffusion coefficient (ADC) in detecting ulcerative colitis (UC). METHODS: A total of 20 patients who underwent 3T magnetic resonance imaging (MRI) without bowel preparation and colonoscopy within 24 h were recruited. Biochemical indexes, including C-reactive protein (CRP), erythrocyte sedimentation rate, hemoglobin, leucocytes, platelets, serum iron and albumin, were determined. Biochemical examinations were then performed within 24 h before or after MR colonography was conducted. DWI was performed at various b values (b = 0, 400, 600, 800, and 1000 s/mm(2)). Two radiologists independently and blindly reviewed conventional- and contrast-enhanced MR images, DWI and ADC maps; these radiologists also determined ADC in each intestinal segment (rectum, sigmoid, left colon, transverse colon, and right colon). Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of DWI hyperintensity from various b factors, ADC values and different radiological signs to detect endoscopic inflammation in the corresponding bowel segment. Optimal ADC threshold was estimated by maximizing the combination of sensitivity and specificity. MR findings were correlated with endoscopic results and clinical markers; these findings were then estimated by ROC analysis. RESULTS: A total of 100 segments (71 with endoscopic colonic inflammation; 29 normal) were included. The proposed total magnetic resonance score (MR-score-T) was correlated with the total modified Baron score (Baron-T; r = 0.875, P < 0.0001); the segmental MR score (MR-score-S) was correlated with the segmental modified Baron score (Baron-S; r = 0.761, P < 0.0001). MR-score-T was correlated with clinical and biological markers of disease activity (r = 0.445 to 0.831, P < 0.05). MR-score-S > 1 corresponded to endoscopic colonic inflammation with a sensitivity of 85.9%, a specificity of 82.8% and an area under the curve (AUC) of 0.929 (P < 0.0001). The accuracy of DWI hyperintensity was significantly greater at b = 800 than at b = 400, 600, or 1000 s/mm(2) (P < 0.05) when endoscopic colonic inflammation was detected. DWI hyperintensity at b = 800 s/mm(2) indicated endoscopic colonic inflammation with a sensitivity of 93.0%, a specificity of 79.3% and an AUC of 0.867 (P < 0.0001). Quantitative analysis results revealed that ADC values at b = 800 s/mm(2) differed significantly between endoscopic inflamed segment and normal intestinal segment (1.56 ± 0.58 mm(2)/s vs 2.63 ± 0.46 mm(2)/s, P < 0.001). The AUC of ADC values was 0.932 (95% confidence interval: 0.881-0.983) when endoscopic inflammation was detected. The threshold ADC value of 2.18 × 10(-3) mm(2)/s indicated that endoscopic inflammation differed from normal intestinal segment with a sensitivity of 89.7% and a specificity of 80.3%. CONCLUSION: DWI combined with conventional MRI without bowel preparation provides a quantitative strategy to differentiate actively inflamed intestinal segments from the normal mucosa to detect UC.

Cytotoxicity assessment of functionalized CdSe, CdTe and InP quantum dots in two human cancer cell models.

The toxicity of quantum dots (QDs) has been extensively studied over the past decade. Some common factors that originate the QD toxicity include releasing of heavy metal ions from degraded QDs and the generation of reactive oxygen species on the QD surface. In addition to these factors, we should also carefully examine other potential QD toxicity causes that will play crucial roles in impacting the overall biological system. In this contribution, we have performed cytotoxicity assessment of four types of QD formulations in two different human cancer cell models. The four types of QD formulations, namely, mercaptopropionic acid modified CdSe/CdS/ZnS QDs (CdSe-MPA), PEGylated phospholipid encapsulated CdSe/CdS/ZnS QDs (CdSe-Phos), PEGylated phospholipid encapsulated InP/ZnS QDs (InP-Phos) and Pluronic F127 encapsulated CdTe/ZnS QDs (CdTe-F127), are representatives for the commonly used QD formulations in biomedical applications. Both the core materials and the surface modifications have been taken into consideration as the key factors for the cytotoxicity assessment. Through side-by-side comparison and careful evaluations, we have found that the toxicity of QDs does not solely depend on a single factor in initiating the toxicity in biological system but rather it depends on a combination of elements from the particle formulations. More importantly, our toxicity assessment shows different cytotoxicity trend for all the prepared formulations tested on gastric adenocarcinoma (BGC-823) and neuroblastoma (SH-SY5Y) cell lines. We have further proposed that the cellular uptake of these nanocrystals plays an important role in determining the final faith of the toxicity impact of the formulation. The result here suggests that the toxicity of QDs is rather complex and it cannot be generalized under a few assumptions reported previously. We suggest that one have to evaluate the QD toxicity on a case to case basis and this indicates that standard procedures and comprehensive protocols are urgently needed to be developed and employed for fully assessing and understanding the origins of the toxicity arising from different QD formulations.

Folic acid-conjugated organically modified silica nanoparticles for enhanced targeted delivery in cancer cells and tumor in vivo.

In this work, we report the synthesis of dye-loaded and folic acid (FA)-conjugated organically modified silica (ORMOSIL) nanoparticles as targeted optical nanoprobes for in vitro and in vivo imaging. The dye-loaded ORMOSIL (ORMD) nanoparticles are synthesized by a facile aqueous phase (oil-in-water microemulsion) approach and they have an average size of 30 nm. We observed that the functionalization of FA onto the particle surface led to a strong cellular uptake of FA-conjugated ORMD nanoparticles for pancreatic cancer Miapaca-2 cells and hepatoma SMMC7721 cells with FA receptor overexpression. Such a trend is not observed for 293T cells and breast cancer MCF7 cells as these cells possess low-expression of the FA receptor. The in vivo imaging studies demonstrate that FA-ORMD nanoparticles are preferentially accumulated in tumor sites. Histological studies reveal that no-ill effects are observed in the major organs of treated mice when compared to the untreated ones. Because of the facile synthesis process, high specificity for tumor targeting and low toxicity of FA-ORMD nanoparticles, significant potential for early-cancer detection application is expected.