Inhibitory potential of iRGD peptide-conjugated garcinol-loaded biodegradable nanoparticles in rat colorectal carcinoma

Paul, Barnali; Gaonkar, Raghuvir H.; Dutta, Debasmita; Dasi, Rajesh; Mukherjee, Biswajit; Ganguly, Shantanu; Das, Sujoy

doi:10.1016/j.msec.2022.112714

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…Thus, the Lys 5 –Gly 6 bond is easily accessible for proteolytic cleavage, which releases the NRP-1-recognizing CendR/K sequence (CRGDK). On the other hand, the solvent exposure of the Cys 9 carboxylate explains why the bioconjugation of this group with bulky molecules, for either therapeutic or diagnostic purposes, is safely permitted. − Both of these findings strengthen the reliability and increase the scientific impact of the obtained atomistic i RGD–integrin binding complexes.…”

Section: Resultsmentioning

confidence: 93%

“…For these reasons, anticancer compounds often need to be administered at high doses to exert relevant pharmacological effects, with the rise of serious adverse reactions. − A feasible solution to the tissue penetration problem is represented by smart carriers that can vehicle the desired drug to extravascular cancer tissue. Carriers of different natures have been developed such as gold nanoparticles, − liposomes, , polymer micelles, or receptor-selective peptides. − In this context, Ruoslahti and co-workers identified an RGD integrins-targeting cyclic nonapeptide, namely, i RGD (internalizing RGD, CRGDKGPDC, 1 Chart ), endowed with remarkable tumor-homing properties. , Notably, this peptide can improve the tumor penetration and efficacy of chemotherapeutics through two alternative mechanisms. ,− In fact, i RGD can be either covalently bioconjugatedusually functionalizing the C-terminal Cys 9 to organic and peptidic drugs or attached to the surface of other delivering systems like nanoparticles, liposomes, or oncolytic viruses. − On the other hand, the tumor endocytosis of cytotoxic agents such as cisplatin, gemcitabine, doxorubicin, nab-paclitaxel, and trastuzumab is enhanced by the simple coadministration of 1 . ,, As a result, hundreds of distinct applications involving i RGD have been published during the past decade, − claiming the p...…”

Section: Introductionmentioning

confidence: 99%

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Molecular View on the iRGD Peptide Binding Mechanism: Implications for Integrin Activity and Selectivity Profiles

D’Amore,

Donati,

Lenci

et al. 2023

J. Chem. Inf. Model.

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Receptor-selective peptides are widely used as smart carriers for specific tumor-targeted delivery. A remarkable example is the cyclic nonapeptide iRGD (CRGDKPGDC, 1) that couples intrinsic cytotoxic effects with striking tumor-homing properties. These peculiar features are based on a rather complex multistep mechanism of action, where the primary event is the recognition of RGD integrins. Despite the high number of preclinical studies and the recent success of a phase I trial for the treatment of pancreatic ductal adenocarcinoma (PDAC), there is little information available about the iRGD three-dimensional (3D) structure and integrin binding properties. Here, we re-evaluate the peptide’s affinity for cancer-related integrins including not only the previously known targets αvβ3 and αvβ5 but also the αvβ6 isoform, which is known to drive cell growth, migration, and invasion in many malignancies including PDAC. Furthermore, we use parallel tempering in the well-tempered ensemble (PT-WTE) metadynamics simulations to characterize the in-solution conformation of iRGD and extensive molecular dynamics calculations to fully investigate its binding mechanism to integrin partners. Finally, we provide clues for fine-tuning the peptide’s potency and selectivity profile, which, in turn, may further improve its tumor-homing properties.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Molecular View on the iRGD Peptide Binding Mechanism: Implications for Integrin Activity and Selectivity Profiles

D’Amore,

Donati,

Lenci

et al. 2023

J. Chem. Inf. Model.

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“…For example, by using functional polymers like poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG), mucus-penetrating properties can be gained [ 278 ]. PLGA was exploited to enhance the performance of IBD treatments [ 280 , 281 , 282 , 283 ], including the case of mucositis, an inflammatory condition of the intestinal mucosa [ 284 ], and in colon cancer therapy [ 285 , 286 , 287 , 288 , 289 , 290 , 291 ]. Naserifar et al designed a drug delivery system consisting of folic acid-conjugated PLGA NPs to deliver resveratrol to intestinal cells [ 292 ].…”

Section: Resultsmentioning

confidence: 99%

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

Garbati,

Picco,

Magrassi

et al. 2024

Pharmaceutics

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The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical–chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies.

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