scholarly journals Design of an Amphiphilic Poly(aspartamide)-mediated Self-assembled Nanoconstruct for Long-Term Tumor Targeting and Bioimaging

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 885 ◽  
Author(s):  
Kondareddy Cherukula ◽  
Saji Uthaman ◽  
In-Kyu Park
Keyword(s):  
Cancer Cells ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Systemic Circulation ◽  
Systemic Clearance ◽  
Tumor Endothelium ◽  
Αvβ3 Integrins ◽  
Tumor Homing

Biodegradable polymers have been developed for the targeted delivery of therapeutics to tumors. However, tumor targeting and imaging are usually limited by systemic clearance and non-specific adsorption. In this study, we used poly(amino acid) derivatives, such as poly(succinimide), to synthesize a nanomicelle-forming poly(hydroxyethylaspartamide) (PHEA, P) modified sequentially with octadecylamine, polyethylene glycol (PEG, P), and glycine (G) to design PHEA-PEG-glycine (PPG) nanoparticles (NPs). These PPG NPs were further tethered to cyclic Arg-Gly-Asp (cRGD) sequences for formulating tumor-targeting PPG-cRGD NPs, and then loaded with IR-780 dye (PPG-cRGD-IR-780) for visualizing tumor homing. cRGD cloaked in PPG NPs could bind specifically to both tumor endothelium and cancer cells overexpressing αvβ3 integrins. PPG-cRGD NPs exhibited enhanced physiological stability, cellular viability, and targeted intracellular uptake in cancer cells. In addition, PPG-cRGD NPs offered enhanced systemic circulation, leading to preferential tumor targeting and prolonged fluorescence tumor imaging for nearly 30 days. Nevertheless, non-targeted formulations demonstrated premature systemic clearance with short-term tumor imaging. Histochemical analysis showed no damage to normal organs, reaffirming the biocompatibility of PHEA polymers. Overall, our results indicated that PPG-cRGD NPs, which were manipulated to obtain optimal particle size and surface charge, and were complemented with tumor targeting, could improve the targeted and theranostic potential of therapeutic delivery.

scholarly journals Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Milad Yousefvand ◽  
Zahra Mohammadi ◽  
Farzaneh Ghorbani ◽  
Rasoul Irajirad ◽  
Hormoz Abedi ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Superparamagnetic Iron Oxide ◽  
Gnrh Receptors ◽  
Imaging Probes ◽  
Magnetic Resonance Imaging Mri ◽  
Targeted Contrast Agent

In recent years, the conjugation of superparamagnetic iron oxide nanoparticles (SPIONs), as tumor-imaging probes for magnetic resonance imaging (MRI), with tumor targeting peptides possesses promising advantages for specific delivery of MRI agents. The objective of the current study was to design a targeted contrast agent for MRI based on Fe3O4 nanoparticles conjugated triptorelin (SPION@triptorelin), which has a great affinity to the GnRH receptors. The SPIONs-coated carboxymethyl dextran (SPION@CMD) conjugated triptorelin (SPION@CMD@triptorelin) were synthesized using coprecipitation method and characterized by DLS, TEM, XRD, FTIR, Zeta, and VSM techniques. The relaxivities of synthetized formulations were then calculated using a 1.5 Tesla clinical magnetic field. MRI, quantitative cellular uptake, and cytotoxicity level of them were estimated. The characterization results confirmed that the formation of SPION@CMD@triptorelin has been conjugated with a suitable size. Our results demonstrated the lack of cellular cytotoxicity of SPION@CMD@triptorelin, and it could increase the cellular uptake of SPIONs to MDA-MB-231 cancer cells 6.50-fold greater than to SPION@CMD at the concentration of 75 μM. The relaxivity calculations for SPION@CMD@triptorelin showed a suitable r2 and r2/r1 with values of 31.75 mM−1·s−1 and 10.26, respectively. Our findings confirm that triptorelin-targeted SPIONs could provide a T2-weighted probe contrast agent that has the great potential for the diagnosis of GnRH-positive cancer in MRI.

scholarly journals A PMMA bone cement composite that functions as a drug-refillable depot for localized, multi-window chemotherapeutic treatment of bone cancer

2021 ◽  
Author(s):  
Erika L Cyphert ◽  
Nithya Kanagasegar ◽  
Ningjing Zhang ◽  
Greg D Learn ◽  
Horst A von Recum
Keyword(s):  
Compressive Strength ◽  
Bone Cement ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Bone Tumors ◽  
Composite System ◽  
Cement Composite ◽  
International Standards ◽  
Pmma Bone Cement

Standard chemotherapy for primary and secondary bone tumors typically involves systemic administration of chemotherapeutic drugs, such as doxorubicin (DOX). However, non-targeted delivery increases dose requirements, and results in off target toxicity and suboptimal chemotherapeutic efficacy. When chemotherapy is ineffective, substantial resection of tissue and/or total amputation become necessary, a debilitating outcome for any patient. In this work, we developed a proof of concept, nonbiodegradable, mechanically robust, and refillable composite system for chemotherapeutic (i.e. DOX) delivery comprised of poly(methyl methacrylate) (PMMA) bone cement and insoluble polymeric γcyclodextrin (γCD) microparticles. The porosity and compressive strength of DOX-filled PMMA composites were characterized. DOX filling capacity, elution kinetics, cytotoxicity against primary osteosarcoma and lung cancer cells, and refilling capacity of composites were evaluated. PMMA composites containing up to 15wt% γCD microparticles provided consistent, therapeutically-relevant release of DOX with ~100% of the initial DOX released after 100 days. Over the same period, only ~6% of DOX was liberated from PMMA with free DOX. Following prolonged curing, PMMA composites with up to 15wt% γCD surpassed compressive strength requirements outlined by international standards for acrylic bone cements. Compared to DOX filled PMMA, DOX filled PMMA/γCD composites provided long term release with decreased burst effect, correlating to long term cytotoxicity against cancer cells. Refillable properties demonstrated by the PMMA composite system may find utility for treating local recurrences, limiting chemoresistance, and altering drug combinations to provide customized treatment regimens. Overall, findings suggest that PMMA composites have the potential to serve as a platform for the delivery of combinatorial chemotherapeutics to treat bone tumors.

Synthesis and Characterization of ROSA Dye - A Rhodamine B-type Fluorophore, Suitable for Bioconjugation and Fluorescence Studies in Live Cells

2019 ◽  
Vol 26 (10) ◽  
pp. 758-767
Author(s):  
Vicente Rubio ◽  
Vijaya Iragavarapu ◽  
Maciej J. Stawikowski
Keyword(s):  
Quantum Yield ◽  
Cancer Cells ◽  
Fluorescent Probe ◽  
Extinction Coefficient ◽  
Rhodamine B ◽  
Solid Phase ◽  
Total Yield ◽  
Molar Extinction Coefficient ◽  
Αvβ3 Integrin ◽  
Αvβ3 Integrins

Background: Herein we report the multigram-scale synthesis, characterization and application of a rhodamine B-based fluorophore (ROSA) suitable for fluorescent studies in biological applications. This fluorophore is devoid of rhodamine spirolactone formation and furthermore characterized by a high molar extinction coefficient (ϵ=87250 ± 1630 M-1cm-1) and quantum yield (φ) of 0.589 ± 0.070 in water. Reported here is also the application of ROSA towards synthesis of a ROSA-PEG-GRGDS-NH2 fluorescent probe suitable for live cell imaging of αvβ3 integrins for in vitro assays. Objective: The main objective of this study is to efficiently prepare rhodamine B derivative, devoid of spirolactone formation that would be suitable for bioconjugation and subsequent bioimaging. Methods: Rhodamine B was transformed into rhodamine B succinimide ester (RhoB-OSu) using N-hydroxysuccinimide. RhoB-OSu was further coupled to sarcosine to obtain rhodamine Bsarcosine dye (ROSA) in good yield. The ROSA dye was then coupled to a αvβ3 integrin binding sequence using standard solid-phase conditions. Resulting ROSA-PEG-GRGDS-NH2 probe was used to image integrins on cancer cells. Results: The rhodamine B-sarcosine dye (ROSA) was obtained in multigram scale in good total yield of 47%. Unlike rhodamine B, the ROSA dye does not undergo pH-dependent spirolactone/spirolactam formation as compared with rhodamine B-glycine. It is also characterized by excellent quantum yield (φ) of 0.589 ± 0.070 in water and high molar extinction coefficient of 87250 ± 1630 M-1cm-1. ROSA coupling to the RGD-like peptide was proved to be efficient and straightforward. Imaging using standard filters on multimode plate reader and confocal microscope was performed. The αvβ3 integrins present on the surface of live WM-266-4 (melanoma) and MCF- 7 (breast cancer) cells were successfully imaged. Conclusion: We successfully derivatized rhodamine B to create an inexpensive, stable and convenient to use fluorescent probe. The obtained derivative has excellent photochemical properties and it is suitable for bioconjugation and many imaging applications.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar
Keyword(s):  
Cancer Cells ◽  
Cellular Uptake ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Curcumin Nanoparticles ◽  
Cytotoxicity Studies ◽  
Delivery Technique ◽  
Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

scholarly journals Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

2021 ◽  
Vol 22 (15) ◽  
pp. 7948
Author(s):  
Elham Jamshidifar ◽  
Faten Eshrati Yeganeh ◽  
Mona Shayan ◽  
Mohammad Tavakkoli Yaraki ◽  
Mahsa Bourbour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cellular Uptake ◽  
Targeted Delivery ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Silica Layer

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.

scholarly journals Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 321
Author(s):  
Shenghui Zhong ◽  
Peng Liu ◽  
Jinsong Ding ◽  
Wenhu Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
High Dose ◽  
One Pot ◽  
Inflammatory Site ◽  
Pei Nanoparticles ◽  
Toxic Reactions

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.

Targeted Delivery of a Sialic Acid-Blocking Glycomimetic to Cancer Cells Inhibits Metastatic Spread

ACS Nano ◽  
2015 ◽  
Vol 9 (1) ◽  
pp. 733-745 ◽  
Author(s):  
Christian Büll ◽  
Thomas Jan Boltje ◽  
Eric A. W. van Dinther ◽  
Timo Peters ◽  
Annemarie M. A. de Graaf ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Metastatic Spread
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