Targeted Nanoparticles for Colorectal Cancer

This work provides insights over a novel biodegradable polymeric nanosystem made of hyaluronic acid and polyarginine for diaminocyclohexane-platinum (DACHPt) encapsulation. Using mild conditions based on ionic gelation technique, monodispersed blank and DACHPt-loaded nanoparticles with a size of around 200 nm and negative  potential (-35 mV) were obtained. The freeze-drying process was optimized to improve the stability and shelf-life of the developed nanoparticles. After reconstitution, nanoparticles maintained their size showing an association efficiency of around 70 % and a high loading efficacy (8%). In vitro cytotoxicity studies revealed that DACHPt-loaded nanoparticles had a superior anticancer activity compared with oxaliplatin solution. The IC50 was reduced by a factor of two in HT-29 cells (IC50 39 µM vs 74 µM, respectively), and resulted almost 1.3 fold lower in B6KPC3 cells (18µM vs 23µM respectively). Whereas toxic effects of both drugformulations were comparable in the A549 cell line (IC50 11 µM vs 12 µM). DACHPt-loaded nanoparticles were also able to modulate immunogenic cell death (ICD) in vitro. After incubation with B6KPC3 cells, an increase in HMGB1 (high-mobility group box 1) production associated with ATP release occurred. Then, in vivo pharmacokinetic studies were performed after intravenous injection (IV) of DACHPt-loaded nanoparticles and oxaliplatin solution in healthy mice (35.9 µg of platinum equivalent/mouse). An AUC six times higher (24 h*mg/L) than the value obtained following the administration of oxaliplatin solution (3.76 h*mg/L) was found. C max was almost five times higher than the control (11.4 mg/L for NP vs 2.48 mg/L). Moreover, the reduction in volume of distribution and clearance clearly indicated a more limited tissue distribution. A simulated repeated IV regimen was performed in silico and showed no accumulation of platinum from the nanoparticles. Overall, the proposed approach discloses a novel nano-oncological treatment based on platinum derivative with improved antitumor activity in vitro and in vivo stability as compared to the free drug.

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“…Plasma clearance differed by a factor of five, being 0.002 and 0.010 L/h for NP and oxaliplatin solution, respectively. [43].…”

Section: Assessment Of Cd44 Expression At B6kpc3 Cell Surface and Celmentioning

confidence: 99%

Bioinspired hyaluronic acid and polyarginine nanoparticles for DACHPt delivery

Matha

Lollo

Taurino

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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“…NPs have been developed for disease diagnosis and targeted drug delivery systems [63,64]. The human tumor cells lines used in this work study are under constant investigation by other groups that have contributed to information about the behavior, mechanisms and treatment efficacy [45,[58][59][60][61][62][63][64][65][66][67][68][69]. Nanomedicine, emerge as a promising platform for theranostic strategies [65].…”

Section: Cell Migration and Tubulogenesismentioning

confidence: 99%

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Helal-Neto

Silva

Saldanha-Gama

et al. 2019

IJMS

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Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN), of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.

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“…Its classification according to the genetic profile, stage of tumor development, and putative targeting molecules is imperative. [25] By achieving this, the rational administration of precise-targeted nanomedicines containing the most effective drug combination may revolutionize the way cancer is treated.…”

Section: Targeted Gemcitabine Delivery Using Dendrimer Nanoparticles mentioning

confidence: 99%

Peptide‐Modified Dendrimer Nanoparticles for Targeted Therapy of Colorectal Cancer

Carvalho

Maia

et al. 2019

Advanced Therapeutics

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Peptides have recently emerged as a promising class of targeting ligands for specific drug delivery in cancer treatment, which avoid undesirable side effects of the systemic administration of chemotherapeutics. Their conjugation with nanoparticles has been demonstrated to improve the functionality of peptides resulting in a versatile platform for biomedical applications. In this work, the development of carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles functionalized with YIGSR laminin receptor binding peptide for the active targeting and specific delivery of therapeutic agents into colorectal cancer cells is described. The successful functionalization is confirmed by several physico-chemical characterization techniques. The selectivity of the YIGSR-CMCht/PAMAM dendrimer nanoparticles is first validated in vitro using a micropatterned array of 67 kDa laminin receptor. Next, the specificity of YIGSR-CMCht/PAMAM dendrimers nanoparticles toward laminin receptor is further confirmed both in 2D and 3D settings using HCT-116 colorectal cancer cells and L929 fibroblasts in co-culture. Finally, gemcitabine-loaded YIGSR-CMCht/PAMAM dendrimer nanoparticles induce a targeted mortality on HCT-116 cancer cells in a co-culture scenario. Overall, the study shows solid evidence that YIGSR laminin receptor binding peptide coupled to CMCht/PAMAM dendrimer nanoparticles may be employed as an anticancerous target for the specific and intracellular delivery of chemotherapeutic agents.

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Targeted Nanoparticles for Colorectal Cancer

Cited by 132 publications

References 136 publications

Bioinspired hyaluronic acid and polyarginine nanoparticles for DACHPt delivery

Bioinspired hyaluronic acid and polyarginine nanoparticles for DACHPt delivery

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Peptide‐Modified Dendrimer Nanoparticles for Targeted Therapy of Colorectal Cancer

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