Cancer Targeting Potential Research Articles

Development and application of naturally derived, cost-effective CQDs with cancer targeting potential.

Carbon quantum dots (CQDs) derived from natural sources have obtained potential interest in biomedical imaging and therapy because of their excellent biocompatibility properties, which include water solubility, simple synthesis and low cytotoxicity. Here the cytotoxicity of ethylene-diamine doped carbon quantum dots (N-CQDs) delivered to breast cancer MCF-7 cells was investigated. Folic acid was used to raise folate recognition and increase FA-NCQD accumulation in the cells, then apoptosis was assayed using nuclear fragmentation, acridine orange labeling, fluorescence imaging, flow cytometry, and caspase 3 expression. The data show that functionalization of these CQDs, derived from a natural source, have potential application in eliminating cancer cells, as shown here for the invasive breast cancer cells, MCF-7. This nano-delivery system provides a novel target therapy possibility therapeutic approach for cancer cells.

Cancer targeting potential of bioinspired chain like magnetite (Fe3O4) nanostructures

Iron is significant, earth abundant and inexpensive materials in everyday use. Non toxicity and clean manufacturing process is still a challenging role in scientific world. The chain like Fe3O4 nanostructures were synthesized using the mixtures such as iron nitrate and Rambutan. Magnetite Fe3O4 was verified using X-ray powder diffraction (XRD). Metal oxide (Fe–O) and A1g and Eg phonon modes are substantiated employing Fourier-transform infrared spectroscopy (FTIR) and Raman spectra. A product chemical state was investigated by high resolution X-ray photoelectron spectroscopy (XPS) spectra. Chain like morphology and polycrystalline nature is attributed by transmission electron microscopy (TEM) analysis. Weight loss activity was revealed through thermogravimetric analysis (TGA) analysis. In application studies, higher concentration of Fe3O4 nanostructures was more effective than the low concentration. Moreover, cytotoxicity effects and cell viability on human cancer cell lines were observed and tested for cancer treatment.

Bioinspired Polymerization of Quercetin to Produce a Curcumin-Loaded Nanomedicine with Potent Cytotoxicity and Cancer-Targeting Potential in Vivo.

Nanomedicine has had a profound impact on the treatment of many diseases, especially cancer. However, synthesis of multifunctional nanoscale drug carriers often requires multistep coupling and purification reactions, which can pose major scale-up challenges. Here, we leveraged bioinspired oxidation-triggered polymerization of catechols to synthesize nanoparticles (NPs) from the plant polyphenol quercetin (QCT) loaded with a hydrophobic anticancer drug, curcumin, and functionalized with poly(ethylene glycol) (PEG) for steric stabilization in one reaction step. NPs were formed by base-catalyzed oxidative self-polymerization of QCT in the presence of curcumin and thiol-terminated PEG upon mixing in a universal solvent (dimethyl sulfoxide), followed by self-assembly with the gradual addition of water. Dynamic light scattering and X-ray photoelectron spectroscopy were used to confirm NP PEGylation. Drug loading was verified by UV-vis spectroscopy. Curcumin-loaded NPs were efficiently internalized by CT26 murine colon cancer cells as determined by flow cytometry and confocal microscopy. NPs also demonstrated sustained release and potent cytotoxicity in vitro. Moreover, in vivo imaging of CT26 tumor-bearing Balb/c mice following tail vein injection of DiR-labeled QCT NPs showed steady tumor accumulation of the NPs up to 24 h. This was further supported by significant tumor uptake of curcumin-loaded QCT NPs as measured by flow cytometry analysis of tumor homogenates. Our findings present a greener synthetic route for the fabrication of drug-loaded surface-functionalized NPs from poorly water-soluble plant polyphenols such as QCT as promising anticancer delivery systems.

ASSESSMENT OF CANCER TARGETING POTENTIAL OF DOXORUBICIN CONJUGATED WITH SURFACE FUNCTIONALIZED MULTI-WALLED CARBON NANOTUBES

Our main aim in the present investigation was to assess the cancer targeting potential of doxorubicin conjugated with folic acid (FA), ethylene di-amine (EDA) and surface F- MWCNTs (FA-EDA-MWCNTs- DOX) conjugate employing on MCF-7 (breast cancer cell line) for efficient tumor targeting. We developed a highly effective novel targeted drug delivery based on DOX-conjugated with the surface of F-MWCNTs by using nucleophilic substitution reaction mechanism and evaluated in facile strategy for cancer treatment. The in vitro drug release study shows that the percentage of drug release under an acidic condition pH-5.4 is higher than that under normal physiological conditions. The FA-EDAMWCNTs- DOX nano-conjugate affords higher efficacy in tumor growth suppression due to its stealth nature and most preferentially taken up by cultured MCF-7 cells through receptor-mediated endocytosis mechanism. Fourier Transform Infrared Spectroscopy (FTIR), UV-Visible Spectroscopy, Nuclear Magnetic Resonance Spectroscopy (NMR) and Scanning Electron Microscopy (SEM) measurements clearly confirmed the functionalization & conjugation steps. The results concluded that developed watersoluble nano-conjugate might emerge as “safe and effective” nano-medicine in cancer treatment by minimizing the side effects with generally regarded as a safe prominence.

Cancer Targeting Potential of 99mTc-Finasteride in Experimental Model of Prostate Carcinogenesis.

This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with 99mTc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the 99mTc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that 99mTc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.

Illuminating the cancer-targeting potential of near-infrared photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cell-selective cancer therapy with enormous potential for treating cancer in a variety of ways. NIR-PIT not only kills cancer cells, but can also eliminate other unfavourable cells including cancer stem cells and immunosuppressor cells, among others, without damaging favourable cells such as immune cells, vascular cells and tissue stem cells. This technique can efficiently activate anti-tumour host immunity in a way that can even cure untreated distant metastasis.

Evaluation of 99m Tc-resveratrol as a colon cancer targeting probe.

The study aimed to evaluate cancer-targeting potential of a newly synthesised radiopharmaceutical, 99m Tc-resveratrol invivo, using colon cancer model. Colon cancer was induced in 20 male Sprague-Dawley rats by subcutaneous administration of 1,2-dimethylhydrazine (DMH), dissolved in 1mM EDTA-normal saline, at a dose of 30mg/kg body weight twice a week for first 4weeks and once a week for next 12weeks. A control group containing normal rats was used for result comparison. Colon cancer in DMH-treated group was confirmed by gross analysis of the colon, by histopathological analysis and molecular marker study in tumour tissue. At the end of the treatment period, the animals from the two groups were used for bio-distribution evaluation of 99m Tc-resveratrol at different time intervals. High uptake of 99m Tc-resveratrol was recorded in rat liver, spleen and kidneys, and the ratio of colon tumour uptake to normal colon uptake in DMH-treated rats increased significantly (P≤0.01) with time, to reach a maximum value at 2h but decreased thereafter. High uptake at the tumour site as compared to normal colon tissue was observed; however, the uptake by cancer cells at the target site was limited by high reticulo-endothelial uptake and rapid metabolism.

Effect of functionalization on drug delivery potential of carbon nanotubes

The main aim of the present investigation was to explore the effect of functionalization on drug delivery potential of carbon nanotubes (CNTs) and to compare the in vitro and in vivo cancer targeting potential of doxorubicin HCL (DOX)-loaded ox-/multi-walled CNTs (MWCNTs), DOX-loaded PEG-MWCNTs and DOX-loaded FA-PEG-MWCNTs. The DOX/PEG-FA-MWCNTs showed enhanced cytotoxicity and were most preferentially taken up by the cancerous cells. The obtained results also support the extended resistance time and sustained release profile of drug-loaded surface-engineered MWCNTs. Overall, we concluded that the developed MWCNTs nanoformulations have higher cancer targeting potential.

Cancer targeting propensity of folate conjugated surface engineered multi-walled carbon nanotubes

Our main aim in the present investigation was to investigate the cancer targeting potential of docetaxel (DTX) loaded, folic acid (FA) terminated, poly (ethylene glycol) (PEG) conjugated, surface engineered multi walled carbon nanotubes (DTX/FA-PEG-MWCNTs) in tumor bearing Balb/c mice. The percent loading efficiency of DTX/FA-PEG-MWCNTs and DTX loaded MWCNTS (DTX/MWCNTs) was calculated to be 93.40±3.82% and 76.30±2.62%, respectively. Flow cytometry analysis suggested that the DTX/FA-PEG-MWCNTs arrested MCF-7 cells’ cycle in the G2 phase and was more cytotoxic as compared to DTX/MWCNTs as well as free drug solution. The obtained pharmacokinetic parameters clearly describe the biocompatibility of engineered nanotubes to degree of functionalization and ability for prolonged residence inside the body. DTX/FA-PEG-MWCNTs was found to be significantly more efficient in tumor suppression as compared with plain MWCNTs (non-targeted) as well as drug solution owing to the enhanced drug release from endosomes after internalization. The DTX/FA-PEG-MWCNTs showed highly significant prolonged survival span (40 days) as compared to DTX/MWCNTs (24 days), free DTX (19 days) and control group (12 days). Overall, we can conclude that the DTX/FA-PEG-MWCNTs shows higher cancer targeting propensity vis a vis minimal side effects in tumor bearing Balb/c mice.

The cancer targeting potential of d-α-tocopheryl polyethylene glycol 1000 succinate tethered multi walled carbon nanotubes

Our main aim in the present investigation was to explore the in vitro and in vivo cancer targeting potential of the doxorubicin (DOX) laden d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) tethered surface engineered MWCNTs nanoformulation (DOX/TPGS-MWCNTs) and compare it with pristine MWCNTs and free doxorubicin solution. The developed MWCNTs nanoformulations were extensively characterized by Fourier-transform infrared, Raman spectroscopy, x-ray diffraction, electron microscopy, and in vitro and in vivo studies using MCF-7 cancer cell line. The entrapment efficiency was determined to be 97.2 ± 2.50% (DOX/TPGS-MWCNTs) and 92.5 ± 2.62% (DOX/MWCNTs) ascribed to π-π stacking interactions. The developed formulations depicted the sustained release pattern at the lysosomal pH (pH 5.3). The DOX/TPGS-MWCNTs showed enhanced cytotoxicity, cellular uptake and were most preferentially taken up by the cancerous cells via endocytosis mechanism. The DOX/TPGS-MWCNTs nanoconjugate depicted the significantly longer survival span (44 days, p < 0.001) than DOX/MWCNTs (23 days), free DOX (18 days) and control group (12 days). The obtained results also support the extended residence time and sustained release profile of the drug loaded surface engineered nanotubes formulations in body as compared to DOX solution. Overall we can conclude that the developed MWCNTs nanoconjugate have higher cancer targeting potential on tumor bearing Balb/c mice.

Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague–Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

Low density lipoproteins mediated nanoplatforms for cancer targeting

Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quanti- tative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

Development, characterization and cancer targeting potential of surface engineered carbon nanotubes

The aim of the present study was to assess the in vitro and in vivo potential of doxorubicin-loaded, folic acid appended engineered multi-walled carbon nanotubes (DOX/FA-PEG-MWCNTs) for efficient tumor targeting. The loading efficiency was determined to be 92.0 ± 0.92 (DOX/FA-PEG-MWCNTs) in phosphate buffer solution (pH 7.4) ascribed to π–π stacking interaction. The developed nanoconjugates were evaluated for in vitro DOX release, erythrocytes toxicity, ex vivo cytotoxicity and cell uptake studies on MCF-7 (breast cancer cell line). The DOX/FA-PEG-MWCNTs nanoconjugate affords higher efficacy in tumor growth suppression due to its stealth nature and most preferentially taken up by the cultured MCF-7 through caveolae-mediated endocytosis as compared to free DOX. The in vivo studies were performed to determine the pharmacokinetics, biodistribution and antitumor efficacy on tumor bearing female Sprague Dawley rats and improved pharmacokinetics confirm the function of FA-PEG conjugated CNTs. The median survival time for tumor bearing rats treated with DOX/FA-PEG-MWCNTs (30 d) was extended very significantly as compared to free DOX (p < 0.001). The results concluded that developed water-soluble nano-conjugates might emerge as “safe and effective” nano-medicine in cancer treatment by minimizing the side effects with and Generally Regarded as Safe prominence.

Cancer Targeting Potential of Folate Targeted Nanocarrier under Comparative Influence of Tretinoin and Dexamethasone

The objective of this investigation was aimed to explore the cancer targeting potential of folate conjugated dendrimer (polypropylene imine, PPI) under strategic influence of folate receptor up-regulators (all trans Retinoic acid, ATRA and Dexamethasone, DEXA). The folate conjugated dendrimer nanoconjugate (FPPI) was synthesized and characterized by FTIR, and (1)H-NMR spectroscopy. The cell line studies investigations were performed on MCF-7 cells. ATRA and DEXA caused 2.17 and 1.65 folds selective up-regulation of folate receptor respectively, when compared with untreated control, after 48 h of pretreatment. ATRA caused 50.47±2.11% more up regulation of folate receptor, than DEXA treated cell. Both up regulators showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC50 values of naked docetaxel (DTX) and DTX loaded dendrimer (PPI-DTX) were found to be 678.93±11.99 nM and 663.51±15.23 nM, respectively, while DTX loaded folate-anchored dendrimer (FPPI-DTX) showed a selectively lowered IC50 value of 468.56±20.86 nM. FPPI-DTX further showed a significant reduction in IC50 value in ATRA and DEXA pretreated cells, wherein IC50 values of 184.21 nM and 290.40±14.05 nM, respectively were observed. The study also concludes ATRA to be a superior receptor up-regulator as well as promoter of folate based targeting compared to DEXA.

Lipoprotein-Inspired Nanoparticles for Cancer Theranostics

Over hundreds of millions of years, animals have evolved endogenous lipoprotein nanoparticles for shuttling hydrophobic molecules to different parts of the body. In the last 70 years, scientists have developed an understanding of lipoprotein function, often in relationship to lipid transport and heart disease. Such biocompatible, lipid–protein complexes are also ideal for loading and delivering cancer therapeutic and diagnostic agents, which means that lipoprotein and lipoprotein-inspired nanoparticles also offer opportunities for cancer theranostics. By mimicking the endogenous shape and structure of lipoproteins, the nanocarrier can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body’s defenses. The small size (less than 30 nm) of the low-density (LDL) and high-density (HDL) classes of lipoproteins allows them to maneuver deeply into tumors. Furthermore, lipoproteins can be targeted to their endogenous receptors, when those are implicated in cancer, or to other cancer receptors.In this Account, we review the field of lipoprotein-inspired nanoparticles related to the delivery of cancer imaging and therapy agents. LDL has innate cancer targeting potential and has been used to incorporate diverse hydrophobic molecules and deliver them to tumors. Nature’s method of rerouting LDL in atherosclerosis provides a strategy to extend the cancer targeting potential of lipoproteins beyond its narrow purview. Although LDL has shown promise as a drug nanocarrier for cancer imaging and therapy, increasing evidence indicates that HDL, the smallest lipoprotein, may also be of use for drug targeting and uptake into cancer cells. We also discuss how synthetic HDL-like nanoparticles, which do not include human or recombinant proteins, can deliver molecules directly to the cytoplasm of certain cancer cells, effectively bypassing the endosomal compartment. This strategy could allow HDL-like nanoparticles to be used to deliver drugs that have increased activity in the cytoplasm. Lipoprotein nanoparticles have evolved to be ideal delivery vehicles, and because of that specialized function, they have the potential to improve cancer theranostics.

Cancer targeting potential of some ligand-anchored poly(propylene imine) dendrimers: a comparison

The present investigation was aimed at developing and comparing the cancer-targeting potential of ligand-anchored dendrimers. Folate-, dextran-, and galactose-anchored poly(propylene imine) dendrimers were synthesized and characterized. Dendritic formulations were evaluated for ex vivo cytotoxicity on HeLa and SiHa cell lines. Flow cytometry studies were performed on the HeLa cell line. An ex vivo MTT assay on HeLa cells indicated IC 50 values of 0.05, 0.2, 0.8, and 0.08 μM for folate, dextran, and galactose formulations, and for free paclitaxel (PTX), respectively. An analogous observation was carried out in SiHa cells, where IC 50 values of 0.6, 0.8, 10, and 6 μM were observed by folate, dextran, and galactose formulations, and free PTX, respectively. The outcome of the MTT assay and flow cytometry suggested the order of targeting potential of various ligands under investigation as folate > dextran > galactose. The outcome is deemed to be of scientific value and is believed to assist drug delivery scientists during selection of targeting ligands. From the Clinical Editor The cancer targeting potential of folate, dextran and galactose functionalized polypropyleneimine (PPI) dendrimers was studied by this group of investigators, reporting the order of targeting potential as folate > dextran > galactose.

Update on Carbon Nanotube Toxicity

Update on Carbon Nanotube Toxicity

Glycoforms obtained by expression in Pichia pastoris improve cancer targeting potential of a recombinant antibody-enzyme fusion protein.

MFE-CP is a recombinant antibody-enzyme fusion protein used for antibody-mediated delivery of an enzyme to cancer deposits. After clearance from normal tissues, the tumor-targeted enzyme is used to activate a subsequently administered prodrug to give a potent cytotoxic in the tumor. MFE-CP localizes to cancer deposits in vivo, but we propose that its therapeutic potential could be improved by N-glycosylation, obtained by expression in Pichia pastoris. Glycosylation could enhance clearance from healthy tissue and result in better tumor:normal tissue ratios. To test this, glycosylated MFE-CP was expressed and purified from P. pastoris. The resultant MFE-CP fusion protein was enzymatically active and showed enhanced clearance from normal tissues in vivo. Furthermore, it showed effective tumor localization. This favorable glycosylation pattern was analyzed by tandem mass spectrometry. High-resolution, high-detection sensitivity collision-induced dissociation experiments proved essential for this task. Results showed that of the three potential N-glycosylation sites only two were consistently occupied with oligomannose structures. Asn-442 appeared the most heterogeneously populated with oligomannose carbohydrates extending from 5 to 13 units in length. Asn-484 was found only in its nonglycosylated form. There was less heterogeneity at Asn-492, which was glycosylated with oligosaccharide structures ranging from 8 to 10 mannose units. Nonglycosylated forms of Asn-442 and Asn-492 were not observed.