Self-assembled nanoparticles from hyaluronic acid–paclitaxel prodrugs for direct cytosolic delivery and enhanced antitumor activity

Xu, Chaoran; He, Wei; Lv, Yaqi; Qin, Chao; Shen, Lingjia; Yin, Lifang

doi:10.1016/j.ijpharm.2015.07.069

Cited by 49 publications

(29 citation statements)

References 32 publications

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“…MATT/CN complexes were first prepared by the following procedure: 7.2 mg of CN was dissolved in 6 mL of water, stirred to give a homogeneous solution and cooled down below 4 °C, followed by the addition of MATT aqueous solution (0.8 mL, 3.75 mg/mL) and treatment using an ultrasonic probe (Scientz Biotechnology Co., Ltd., Ningbo, China) at 360 W for 10 min. HA-PTX prodrug was synthesized as described in our previous report 10 . HPMC NPs were prepared by mixing 3 mg of HA-PTX dissolved in 500 μL of water with the prepared MATT/CN complex solution under gentle stirring for 1 min and ultrasonic treatment for 10 min at 360 W. The temperature during the preparation period was controlled below 4 °C.…”

Section: Methodsmentioning

confidence: 99%

“…However, both drugs are poorly water-soluble compounds, and co-delivery of them is challenging. Here, we used the following strategies to address the solubility issue: (i) Hyaluronic acid (HA) is a natural and biodegradable polymer and, importantly, can target CD44 receptors overexpressed on cancer cells 10 - 12 . Therefore, a HA-PTX prodrug was synthesized for enhanced solubility and CD44 targeting.…”

Section: Introductionmentioning

confidence: 99%

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Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Zhao

Zhu

et al. 2018

Theranostics

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Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs.Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra. The developed nanoplatform was characterized via dynamic light scattering and transmission electron microscopy, and was evaluated in terms of MMP-sensitive release and stability. Subsequently, the cellular uptake, trafficking, and in vitro invasion were studied by flow cytometry, confocal laser microscopy and transwell assay. MMP expression and activity was determined by western blotting and gelatin zymography. Finally, the studies of biodistribution and antitumor efficacy in vivo were performed in a mouse 4T1 tumor breast model, followed by in vivo safety study in normal mouse.Results: The interaction between the prodrug and complexes is strong with a high affinity, resulting in the assembly of these two components into hybrid nanoparticles (250 nm). Compared with extracellular incubation with MATT, HPMC NP treatment markedly reduced the expression (100%) and activity (50%) of MMPs in 4T1 cells and in the tumor. HPMC NPs exhibited 1.4-fold tumor accumulation, inhibited tumor-growth by >8-fold in volume with efficient apoptosis and proliferation, and suppressed metastasis (>5-fold) and angiogenesis (>3-fold). Overall, HPMC NPs were efficient in metastatic cancer therapy. Conclusions: According to the assembly of polymer prodrug and protein-drug complexes, this study offers a new strategy for constructing nanoparticles for targeted drug delivery, biomedical imaging, and combinatorial treatment. Importantly, via inhibition of intracellular MMPs, metastasis and angiogenesis can be potently blocked, benefiting the rational design of nanomedicine for cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Zhao

Zhu

et al. 2018

Theranostics

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“…All the personnel involved wore protective lab coats, face masks, sterile gloves during experimental procedures. A total of 40 μL formulation were injected to each tumor on every 4 th day including 12, 16, 20, 24 and 28 th day and followed till 40th day for tumor growth and regression39.…”

Section: Methodsmentioning

confidence: 99%

Pro-haloacetate Nanoparticles for Efficient Cancer Therapy via Pyruvate Dehydrogenase Kinase Modulation

Misra

Ostadhossein

et al. 2016

Sci Rep

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Anticancer agents based on haloacetic acids are developed for inhibition of pyruvate dehydrogenase kinase (PDK), an enzyme responsible for reversing the suppression of mitochondria-dependent apoptosis. Through molecular docking studies mono- and dihaloacetates are identified as potent PDK2 binders and matched their efficiency with dichloroacetic acid. In silico screening directed their conversion to phospholipid prodrugs, which were subsequently self-assembled to pro-haloacetate nanoparticles. Following a thorough physico-chemical characterization, the functional activity of these novel agents was established in wide ranges of human cancer cell lines in vitro and in vivo in rodents. Results indicated that the newly explored PDK modulators can act as efficient agent for cancer regression. A Pyruvate dehydrogenase (PDH) assay mechanistically confirmed that these agents trigger their activity through the mitochondria-dependent apoptosis.

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“…In the second step, activation of HA was completed with the formation of adipic-dihydrazido functionalized HA (HA-ADH). In the third and final step, both activated moieties were reacted together to produce HA-Ptx conjugate (Xu et al, 2015;Han et al, 2017). The confirmation of conjugation was done by using spectroscopic analysis like, IR and NMR.…”

Section: Synthesis and Characterization Of Ha-ptx Conjugatementioning

confidence: 99%

Development and characterization of RGD embellished drug-conjugate loaded NPs for dual targeting of tumor cells

Asati¹

2019

Asian J Pharm Pharmacol

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Objective: The drug targeting strategy is drawn more attention for the effective treatment of various types of lethal diseases such as, cancer. To improve the efficacy of drug the dual targeted delivery system was developed with the help of hyaluronic acid (HA) and RGD peptide. HA targets the overexpressed CD44 receptors while RGD peptide helps to target integrin (α β) receptors on the tumor cells. Material and Methods: The drug, paclitaxel (Ptx); was used as the v 3 model drug and conjugated with HA and then the drug-HA conjugate was entrapped into the RGD decorated nanoparticulate system. The conjugation of the ligand molecules with the drug and carrier system was confirmed by the IR and NMR spectroscopy methods. Results: The developed NPs exhibited excellent physical properties like, particle size in nano size range, spherical shape, and high entrapment efficiency which may make drug delivery system more efficient. The cytotoxicity and cell uptake study of the prepared formulations on the cancer cell line (U87MG) (which has overexpressed integrin receptors, showed lowest IC value and highest cell uptake) showed better uptake of RGD 50 decorated NPs due to receptor mediated transport across the cells. Conclusion: Thus, RGD peptide decorated system developed as the promising candidate for the treatment of cancer cells, effectively.

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Self-assembled nanoparticles from hyaluronic acid–paclitaxel prodrugs for direct cytosolic delivery and enhanced antitumor activity

Cited by 49 publications

References 32 publications

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Pro-haloacetate Nanoparticles for Efficient Cancer Therapy via Pyruvate Dehydrogenase Kinase Modulation

Development and characterization of RGD embellished drug-conjugate loaded NPs for dual targeting of tumor cells

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