Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy

Viale, Maurizio; Tosto, Rita; Giglio, Valentina; Pappalardo, Giuseppe; Oliveri, Valentina; Maric, Irena; Mariggiò, Maria Addolorata; Vecchio, Graziella

doi:10.1007/s10637-018-0711-9

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…The reduction of DOXO toxic (vesicant and necrotizing) effects of different nanotechnological platforms compared to the free drug has been reported . In light of the interest for DOXO carriers based on CyD derivatives, we investigated the cytotoxicity of DOXO in the presence of the new polymers.…”

Section: Introductionsupporting

confidence: 60%

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Exploring the Functionalization of Polymeric Nanoparticles Based on Cyclodextrins for Tumor Cell Targeting

2019

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Some nanotherapeutics based on cyclodextrin polymers are currently undergoing clinical trials. In light of this interest, we synthesized new linear polymers based on β‐cyclodextrins containing targeting units, such as biotin or arginine, to explore the advantage of functionalization for drug delivery. The polymers increased doxorubicin solubility. Furthermore, they slightly enhanced doxorubicin cytotoxicity in A2780 cells. In particular, the polymer containing arginine moieties was the most effective system by increasing doxorubicin cytotoxicity by 50%.

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Section: Introductionsupporting

confidence: 60%

“…In many cases, supramolecular host‐guest chemistry has been used to add recognition specificity to CyD‐based NPs …”

Section: Introductionmentioning

confidence: 99%

Exploring the Functionalization of Polymeric Nanoparticles Based on Cyclodextrins for Tumor Cell Targeting

2019

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“…CyD based NPs were modified with receptor-specific targeting ligands (peptides, sugars, aptamers or vitamins) which could allow the delivery vehicle to undergo receptor-mediated endocytosis. We have decorated CyD cross-linked polymers with RGD moiety through its functionalization with adamantane [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

et al. 2021

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In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

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“…Studies have been carried out by researchers including the evaluation of the combined effects of berberine and evodiamine on colorectal cancer cells in vitro, 42 and curcumin synergized the action of 5-fluorouracil and oxaliplatin against chemoresistant human cancer colon cells. 43 RGD peptide decorated nanocarriers have been widely used as delivery systems for targeted anti-cancer chemotherapy, 44 and also applied for combinatorial topotecan and quercetin delivery approach for anti-breast cancer cells strategy. 45 In this study, RGD-containing ligand was synthesized by conjugating cRGDfK with TOSD using PEG as a linker to obtain cRGDfK-PEG-TOSD.…”

Section: Discussionmentioning

confidence: 99%

<p>Synergistic Effect of Tangeretin and Atorvastatin for Colon Cancer Combination Therapy: Targeted Delivery of These Dual Drugs Using RGD Peptide Decorated Nanocarriers</p>

He¹,

Zheng

Li³

et al. 2020

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Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the fourth leading cause of cancer death over the world. Nano-sized drug delivery systems are used for the treatment of cancers. The aim of this study was to develop a tangeretin (TAGE) and atorvastatin (ATST) combined nano-system decorated with RGD (RGD-ATST/TAGE CNPs) for colon cancer combination therapy. Materials and Methods: In this study, cyclized arginine-glycine-aspartic acid sequences (RGD) contained ligand was synthesized by conjugating cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfK) with D-α-tocopheryl succinate dichloromethane (TOSD) using polyethylene glycol (PEG) as a linker to obtain cRGDfK-PEG-TOSD. ATST and TAGE combined nanosystems: RGD-ATST/TAGE CNPs were prepared. The combination effects as well as antitumor effects of these two agents were evaluated on colon cancer cells and mice bearing cancer models. Results: Drug entrapment efficiencies of nano-systems were high (around 90%), suggesting the good loading capacity. The release profiles of ATST or TAGE from RGD-ATST/TAGE CNPs followed Higuchi model. The RGD-decorated nano-system showed more obvious cytotoxicity on HT-29 cells than the undecorated nano-system, but no obvious difference was found on normal CCD-18 cells. The strongest synergism was observed when the weight ratio of ATST to TAGE was 1:1. In vivo biodistribution of RGD-ATST/TAGE CNPs in the tumor site is high and prominently inhibited the in vivo tumor growth. Conclusion: The results demonstrated that RGD-ATST/TAGE CNPs showed the most significant synergistic therapeutic efficacy, exhibited no significant toxicity to major organs and tissues, and body weight of the treated mice was stable. Therefore, the combination nano-system is a promising platform for colon cancer therapy.

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Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy

Cited by 17 publications

References 37 publications

Exploring the Functionalization of Polymeric Nanoparticles Based on Cyclodextrins for Tumor Cell Targeting

Exploring the Functionalization of Polymeric Nanoparticles Based on Cyclodextrins for Tumor Cell Targeting

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

<p>Synergistic Effect of Tangeretin and Atorvastatin for Colon Cancer Combination Therapy: Targeted Delivery of These Dual Drugs Using RGD Peptide Decorated Nanocarriers</p>

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