Low molecular weight heparin-all-trans-retinoid acid conjugate as a drug carrier for combination cancer chemotherapy of paclitaxel and all-trans-retinoid acid

Hou, Lin; Fan, Ying; Yao, Jing; Zhou, Jianping; Li, Caocao; Fang, Zhengjie; Zhang, Qiang

doi:10.1016/j.carbpol.2011.06.008

Cited by 60 publications

(51 citation statements)

References 55 publications

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“…As shown in Figure 3A, GA-HRA displayed almost no hemolytic effect, suggesting that GA-HRA was not toxic towards erythrocytes. On the contrary, the hemolysis of GA plus ATRA solution reached 44.5% at 0.2 mg/mL concentration, indicating that the drug encapsulation into nanoparticles would improve the drug biocompatibility by blocking the direct contact of drugs with erythrocytes, as suggested in previous studies 9,31 where low molecular weight heparin-ATRA conjugate and N-octyl-O, N-carboxymethyl chitosan significantly decreased the hemolytic activity of Abbreviations: aTra, all-trans retinoic acid; ga, gambogic acid; ga-hra, ga-loaded hra nanoparticles; ha, hyaluronic acid; hra, hyaluronic acid-g-all-trans retinoic acid.…”

Section: Biocompatibilitymentioning

confidence: 59%

“…The DL (%) and entrapment efficiency (%) of GA were calculated as described previously. 9 The lyophilized nanoparticles were dispersed in 5 mL of 5% glucose solution. The particle size and zeta potential of the nanoparticles were determined by a NanoSight NS500 equipped with the NTA 2.3 analytical software (NanoSight, Amesbury, UK) and dynamic light scattering measurements (BI-200SM; Brookhaven Instruments Corp, Holtsville, NY, USA).…”

Section: Preparation and Characterization Of Ga-hramentioning

confidence: 99%

“…Our previous study has described that the drug loading (DL) of paclitaxel (PTX)-loaded heparin-based nanoparticles was up to 33%. 9 More notably, polymeric nanoparticles could improve the pharmacokinetic and distribution profile (such as longer blood circulation), reduce side effects, and target tumors by enhanced permeability and retention (EPR) effect-based passive mechanisms. [10][11][12] Hyaluronic acid (HA) has gained intense attention due to its superior properties and potential as a drug delivery carrier.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the nanoparticle had high DL% (31.1%) and entrapment efficiency (90.5%) as expected, which further confirm that amphiphilic polymer is an excellent carrier for hydrophobic drugs. 9 The representative atomic force microscopy and transmission electron microscopy images of the nanoparticles are shown in Figure 2C and D. The results showed that the GA-HRA were spherical in shape with uniform size distribution.…”

mentioning

confidence: 96%

“…9,27,28 Therefore, HRA conjugate with a high DS of 11.8 wt% was selected as the representative candidate for further studies.…”

mentioning

confidence: 99%

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Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid

Yao¹,

Li²,

Sun³

et al. 2014

IJN

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In order to enhance the in vivo codelivery efficiency of gambogic acid (GA) and all-trans retinoic acid (ATRA), our strategy was to entrap GA in the self-assembled nanoparticles based on amphiphilic hyaluronic acid (HA)-ATRA (HRA) conjugate. In this way, GA and ATRA were loaded simultaneously in a nanocarrier and codelivered into the tumor cell through HA receptor-mediated endocytosis. GA-loaded HRA nanoparticles (GA-HRA) were prepared by a dialysis method, and their physicochemical characteristics were investigated as well. GA-HRA exhibited a high drug loading capacity (31.1%), had a particle size in the range of 100–150 nm, and good biocompatibility. HRA nanoparticles were effectively internalized by MCF-7 cells and translocated into the nucleus in a time-dependent manner. The in vivo imaging analysis demonstrated that the fluorescent signals in the tumor were markedly increased with DiR-loaded nanoparticles after intravenous administration compared to free DiR solution, suggesting it has excellent tumor targeting properties. More importantly, GA-HRA exhibited excellent in vivo efficacy with dramatically reduced toxicity. In conclusion, with the assistance of HRA nanoparticles, GA and ATRA can successfully realize an effective combination chemotherapy as well as tumor-targeted delivery.

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Section: Biocompatibilitymentioning

confidence: 59%

Section: Preparation and Characterization Of Ga-hramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 96%

“…9,27,28 Therefore, HRA conjugate with a high DS of 11.8 wt% was selected as the representative candidate for further studies.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid

Yao¹,

Li²,

Sun³

et al. 2014

IJN

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Natural and Synthetic Biopolymers in Drug Delivery and Tissue Engineering

Schneible

Daniele

Menegatti

2020

Biopolymers for Biomedical and Biotechnological Applications

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Retracted: Multifunctional Polymeric Nanosystems for Dual‐Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors

Dahmani

Xiao

Zhang

et al. 2016

Adv Healthcare Materials

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Combination of antiangiogenesis and chemotherapy holds vast promise for effective inhibition of tumor proliferation and invasion. Herein, a multifunctional self-assembled nanosystem consisting of amphiphilic c(RGDyK)-functionalized low-molecular-weight heparin-gambogic acid conjugate (cRHG) is developed, using c(RGDyK) peptide as αv β3 integrin targeting moiety to realize a double-targeted delivery to both tumor cells and angiogenic vasculature. cRHG with a markedly decreased anticoagulant activity can self-assemble into nanosized particles (around 150 nm). cRHG nanoparticles effectively inhibit vascular endothelial growth factor (VEGF)-triggered tube-like formation of HUVEC and neovascularization of subcutaneous Matrigel plugs. More importantly, the targeting ability of cRHG nanoparticles is revealed by their efficient internalization by αv β3 integrin-positive cells (U87MG and HUVEC) in vitro and obvious accumulation of Cy7/cRHG in the tumor site with strong fluorescence signals in both cancer cells and neovasculature. Besides, cRHG maintains the in vitro cytotoxic activity of gambogic acid, while achieving the highest in vivo antitumor activity in U87MG mouse xenograft model and displaying better safety profile than free drugs solutions. Mechanistic investigations reveal the substantial inhibition of hypoxia-inducible factor-1 alpha, VEGF, and CD31 expression by cRHG nanoparticles with remarkable down-regulation of VEGFR2 phosphorylation. These results suggest that cRHG nanoparticles provide a versatile nanoplatform for efficacious combinatorial tumor therapy.

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Low molecular weight heparin-all-trans-retinoid acid conjugate as a drug carrier for combination cancer chemotherapy of paclitaxel and all-trans-retinoid acid

Cited by 60 publications

References 55 publications

Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid

Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid

Natural and Synthetic Biopolymers in Drug Delivery and Tissue Engineering

Retracted: Multifunctional Polymeric Nanosystems for Dual‐Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors

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