Effective tumor-targeted delivery of etoposide using chitosan nanoparticles conjugated with folic acid and sulfobetaine methacrylate

RSC Advances ◽  
2016 ◽  
Vol 6 (94) ◽  
pp. 91192-91200 ◽  
Author(s):  
Song Hua ◽  
Jiahua Yu ◽  
Jun Shang ◽  
Haowen Zhang ◽  
Jie Du ◽  
...  
Keyword(s):  
Folic Acid ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Chitosan Nanoparticles

FA–CS(VP-16)-g-PSBMA nanoparticles were synthesized and showed effective tumor-targeting properties and promising anti-tumor capacity in vivo.

scholarly journals Temozolomide encapsulated and folic acid decorated chitosan nanoparticles for lung tumor targeting: improving therapeutic efficacy both in vitro and in vivo

Oncotarget ◽  
2017 ◽  
Vol 8 (67) ◽  
pp. 111318-111332 ◽  
Author(s):  
Kaidi Li ◽  
Naixin Liang ◽  
Huaxia Yang ◽  
Hongsheng Liu ◽  
Shanqing Li
Keyword(s):  
Folic Acid ◽  
Therapeutic Efficacy ◽  
Tumor Targeting ◽  
Lung Tumor ◽  
Chitosan Nanoparticles

scholarly journals Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina
Keyword(s):  
Phage Display ◽  
Cell Sorting ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Search Strategy ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

Novel folate-targeted docetaxel-loaded nanoparticles for tumour targeting: in vitro and in vivo evaluation

RSC Advances ◽  
2016 ◽  
Vol 6 (69) ◽  
pp. 64306-64314 ◽  
Author(s):  
M. H. Han ◽  
Z. T. Li ◽  
D. D. Bi ◽  
Y. F. Guo ◽  
H. X. Kuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Therapy ◽  
Targeted Delivery ◽  
Tumour Targeting ◽  
Breast Cancer Therapy ◽  
In Vivo Evaluation ◽  
Targeted Delivery System

Cholesterol-PEG1000-FA (folic acid) was synthesized as a stabilizer to encapsulate DTX, for the construction of a promising targeted delivery system for breast cancer therapy.

Folic acid conjugated chitosan for targeted delivery of siRNA to activated macrophages in vitro and in vivo

2014 ◽  
Vol 2 (48) ◽  
pp. 8608-8615 ◽  
Author(s):  
Chuanxu Yang ◽  
Shan Gao ◽  
Jørgen Kjems
Keyword(s):  
Folic Acid ◽  
Targeted Delivery ◽  
Activated Macrophages

scholarly journals Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles

2019 ◽  
Vol 20 (21) ◽  
pp. 5458 ◽  
Author(s):  
Kai Zhao ◽  
Dan Li ◽  
Guogang Cheng ◽  
Baozhen Zhang ◽  
Jinyu Han ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Tumor Targeting ◽  
Caspase 3 ◽  
Slow Release ◽  
Normal Cells ◽  
Binding Peptide ◽  
P53 Signaling ◽  
Targeting Delivery ◽  
P53 Signaling Pathway

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

Folic acid modified copper oxide nanoparticles for targeted delivery in in vitro and in vivo systems

RSC Advances ◽  
2015 ◽  
Vol 5 (83) ◽  
pp. 68169-68178 ◽  
Author(s):  
Dipranjan Laha ◽  
Arindam Pramanik ◽  
Sourav Chattopadhyay ◽  
Sandip kumar Dash ◽  
Somenath Roy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Therapy ◽  
Copper Oxide ◽  
Targeted Delivery ◽  
Copper Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Breast Cancer Therapy

Targeted delivery of copper oxide nanoparticles for breast cancer therapy.

scholarly journals Polypeptidic Taxol-Tropins: Targeting paclitaxel to the tumor microenvironment

2021 ◽  
Vol 5 (3) ◽  
pp. 01-11
Author(s):  
Erlinda M. Gordon ◽  
Seiya Liu ◽  
Sant P. Chawla ◽  
Frederick L. Hall
Keyword(s):  
Tumor Microenvironment ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Drug Binding ◽  
Peptide Sequence ◽  
Human Pancreatic Cancer ◽  
Binding Assays ◽  
Agarose Beads

Background and Rationale: Although PTX is widely used as a single chemotherapeutic agent and in various combination regimens, its clinical utility is hindered by acquired drug resistance and serious dose-limiting side effects that result from the ungoverned biodistribution of the taxane. Hypothesis: Conceptually, the precision, validity, and efficiency of paclitaxel delivery to tumor compartments might be substantially improved by “actively targeting” the exposed collagenous (XC-) proteins presented within the tumor microenvironment (TME)—XC-proteins physically exposed by the pathologic biochemical processes of tumor invasion, reactive stroma formation, and neo-angiogenesis. Objective: An adaptive bioengineering approach aims to apply pathotropic tumor-targeting functionality to paclitaxel (PTX), a powerful cytotoxic taxane which exhibits anti-tubulin / anti-mitotic / anti-cancer activities against a broad range of solid tumors. Materials and Methods: Synthetic peptide XC-targeting probes (< 40 aa) and polypeptide aptamers (40 to 53 aa), 85 - 99% purity, were prepared by 9-fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis, purified by high performance liquid chromatography (HPLC), and verified by mass spectrometry and amino acid analysis, and the XC-targeting probes were FITC-labeled. Analysis of fluorescence in XC-binding assays was visualized with an Ultra Bright Blue Light trans-illuminator equipped with an amber filter; photo-documentation was provided by a Leica V-Lux 1 digital camera; and comparative fluorescence was quantified using a Quantus benchtop fluorimeter (Promega). The tumor-targeting properties of Taxol-Tropins were tested in vitro by Taxol-aptamer binding assays and collagen-agarose binding assays and the bioactivities of PTX bound non-covalently toTaxol-Tropin aptamers were tested on XC-agarose beads. Further, the tumor targeting property of the Taxol-Tropin aptamers was tested in vivo in a murine model of metastatic cancer. Results: Here we report on the first actively targeted delivery of paclitaxel utilizing bifunctional polypeptide targeting onco-aptamers, called Taxol-Tropins, which: (i) bind PTX upon simple mixing with suitably high affinities and; (ii) bind exposed XC-proteins, thereby promoting enhanced partitioning and drug delivery into the TME. The bifunctional peptide sequence-optimized Taxol-Tropins bound tightly non-covalently to PTX and also exhibited high affinity and selectivity for XC-agarose beads in vitro. Importantly, the cytotoxic bioactivity of the Taxol-Tropin-bound-PTX molecule was well preserved in cellulo, as was demonstrated by cytocidal activity observed in MDA-MB-231 breast cancer cell cultures. Tumor-targeted PTX delivery by Taxol-Tropin onco-aptamers in vivo was modeled by subcutaneous xenografts of human pancreatic cancer in nude mice: where intense fluorescence of the PTX probe was observed in tumors of mice injected with the Taxol-Tropin-bound-PTX within minutes after intravenous injection, but not in untreated mice or mice treated with non-targeted PTX probe. Conclusions: These results demonstrate the feasibility of pro-actively targeting PTX, a clinically important small molecule, using Taxol-Tropins: synthetic polypeptide onco-aptamers, revealing optimized drug binding sequences and structural modifications pertinent to further clinical development of the tumor-targeting platform which may indeed shift the Therapeutic Index of PTX to one of greater clinical efficacy at lower drug doses.

scholarly journals Paclitaxel-Loaded and Folic Acid Modified PLGA Nanomedicine with Glutathione-Response for the Treatment of Lung Cancer

2020 ◽  
Author(s):  
Zhanxia Zhang ◽  
Wang Yao ◽  
Jialiang Yao ◽  
Fangfang Qian ◽  
Zujun Que ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Folic Acid ◽  
Side Effects ◽  
Targeted Delivery ◽  
Great Promise ◽  
Stimuli Responsive ◽  
Biologically Relevant ◽  
Chemotherapy Agents

Abstract Targeted delivery and smart response of nanomedicine hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemotherapy agents in cancer treatment. While a few research systems about organic nanomedicines with these properties have limited the development prospect of nanomedicines. In the present study, folic acid (FA) targeted delivery and GSH (glutathione) smart responsive nanomedicine was rationally designed for paclitaxel (PTX) delivery in the treatment of lung cancer. Compared with other stimuli responsive nanomedicines, this nano-carrier was not only sensitive to biologically relevant GSH for on demand drug release but also biodegradable into biocompatible by products after fulfilling its delivering task. The nanomedicine can firstly enter into tumor cells via FA and its receptor mediated endocytosis. After lysosomes escape, the PLGA (poly(lactic-co-glycolic acid) nanomedicine was triggered by the higher level of GSH and released its cargo in tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only can inhibit the proliferation and promote the apoptosis of lung cancer cells greatly, but also possesses less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the encouraging potential for multifunctional nano-platform applicable to enhance the bioavailability and reduce the side effects of chemotherapy agents.

Abstract 111: A Kidney Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Cisplatin-induced Nephrotoxicity

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
John D Imig ◽  
Md A Khan ◽  
Adeniyi M Adebesin ◽  
John R Falck
Keyword(s):  
Folic Acid ◽  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Renal Tissue ◽  
Epoxyeicosatrienoic Acid ◽  
High Concentration ◽  
Lower Effective Dose

Epoxyeicosatrienoic acid (EET) analogs have exceptional therapeutic potential to combat cardiovascular and kidney diseases. EET analogs combat damage in acute and chronic kidney disease models. Biological actions attributed to EET analogs such as vasodilation, anti-inflammation, anti-apoptosis, and anti-fibrosis are ideally suited to treat kidney diseases. Although EET analogs have performed well in several in vivo models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic effect in the kidney and obviate possible side effects. For EET analog kidney-targeted delivery, we conjugated an EET analog to folic acid because there is a high concentration of folate receptors in renal tissue. The EET analog was conjugated to folic acid via a PEG-diamine linker. Next, we compared the kidney targeted EET analog, EET-F01, to a well-studied EET analog, EET-A. EET-A or EET-F01 was infused i.v. (10mg/kg/hr) for 6 hours via the rat jugular vein. Plasma and kidney tissue were collected and EET-A or EET-F01 measured by LC-MS-MS. EET-A plasma level was 1.6 ng/mL, but EET-A was undetectable in the kidney. On the other hand, EET-F01 was 6.5 ng/mL in plasma and 26.7 ng/mL in kidney tissue. These data demonstrate that EET-F01 targets the kidney. Experiments were conducted to compare EET-F01 and EET-A to decrease cisplatin-induced nephrotoxicity. A single injection of cisplatin (7 mg/kg ip) was administered to WKY rats treated with vehicle, EET-A (10 mg/kg ip) or EET-F01 (20 mg/kg or 2 mg/kg ip) for five days. Cisplatin increased BUN (125 ± 11 mg/dL) and NAG (12 ± 4 IU/L) compared to control (36 ± 9 mg/dL and 4 ± 1 IU/L). EET-F01 was as effective as EET-A in decreasing BUN, NAG, and renal histological injury five days following cisplatin administration. Despite it almost 2x-greater molecular weight compared with EET-A, EET-F01 was effective in lowering BUN and NAG at 20 mg/kg/d and at a 10-fold lower dose of 2 mg/kg/d. These data clearly demonstrate that EET-F01 targets the kidney and allows for a lower effective dose. In conclusion, we have developed a kidney targeted EET analog, EET-F01, that demonstrates excellent potential as a therapeutic for kidney diseases.

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