RGD-modified PEGylated paclitaxel nanocrystals with enhanced stability and tumor-targeting capability

Huang, Zhigang; Lv, Feng-mei; Wang, Jun; Cao, Shui-juan; Liu, Zhepeng; Liu, Yu; Lu, Weiyue

doi:10.1016/j.ijpharm.2018.12.023

Cited by 51 publications

(18 citation statements)

References 33 publications

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“…The CASF modification and packaging for the RGD.Ad-ING4-IL-24 vector effectively shielded the negative charge on its surface and improved the infection efficiency, leading to the increased expression of the target genes ING4 and IL-24. The RGD peptide, rich in the CASF/Ad complex, has also been shown to induce apoptosis in tumor cells by blocking the adhesion of tumor cells to the extracellular matrix 49. The combined effects brought about the enhancement of hepatoma cell apoptosis induced by the CASF/Ad complex.…”

Section: Discussionmentioning

confidence: 99%

Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

Qu¹,

Wang²,

Feng³

et al. 2019

IJN

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IntroductionCancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.MethodsIn this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.ResultsHuman hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.ConclusionThe CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.

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Section: Discussionmentioning

confidence: 99%

Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

Qu¹,

Wang²,

Feng³

et al. 2019

IJN

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“…When solid materials are immersed in the aqueous solution of dopamine, dopamine polymerizes firmly adsorb on the surface of the solid material [37]. We found that nanocrystals can also act as the solid material on which dopamine polymerized to form PDA coating [32]. Moreover, such a polydopamine film contains active catechol hydroxyl groups, which can further react with amino groups under mild conditions [38], which provided a good active reaction platform for functional modification of nanocrystals.…”

Section: Introductionmentioning

confidence: 97%

“…Recently, we got some inspiration from mussels in the ocean for surface modification of nanocrystals [32]. Mussels rely on the repetitive structure of levodopa in their foot filaments to stick firmly to the bottom of the ship [33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals

Wang

et al. 2020

Molecules

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Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

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“…Currently, anticancer drugs are limited by weak selectivity towards tumour cells and severe side effects on normal tissues . Nano‐drug delivery systems, such as polymeric micelles, liposomes and nanoparticles (NPs), have been used to increase tumour targeting .…”

Section: Introductionmentioning

confidence: 99%

“…Currently, anticancer drugs are limited by weak selectivity towards tumour cells and severe side effects on normal tissues. [1][2][3][4] Nano-drug delivery systems, such as polymeric micelles, liposomes and nanoparticles (NPs), have been used to increase tumour targeting. [5][6][7][8][9] NPs are known to enter tumour cells through the enhanced permeability and retention (EPR) effect due to their small size and large surface area.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride

Zha

Wang

Qian

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein‐DOX NPs) to improve its pH‐sensitive release, bioavailability and decrease cardiotoxicity. Methods HA/Zein‐DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X‐ray diffraction and Fourier‐transform infrared spectroscopy of HA/Zein‐DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo. Key findings The small PDI and high Zeta potential demonstrated that HA/Zein‐DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein‐DOX NPs. HA/Zein‐DOX NPs showed pH‐sensitive release. Compared with free DOX, HA/Zein‐DOX NPs increased cellular uptake which caused 7 times higher in‐vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t1/2β and AUC0–t of HA/Zein‐DOX NPs were 2.73‐ and 3.12‐fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein‐DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%). Conclusion In this study, HA/Zein‐DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.

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RGD-modified PEGylated paclitaxel nanocrystals with enhanced stability and tumor-targeting capability

Cited by 51 publications

References 33 publications

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals

Preparation, characterization and preliminary pharmacokinetic study of pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin hydrochloride

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