Study on different particle sizes of DOX-loaded mixed micelles for cancer therapy

Li, Chenglei; Guan, Hong; Li, Zhaohuan; Wang, Fangqing; Wu, Jingliang; Zhang, Bo

doi:10.1016/j.colsurfb.2020.111303

Cited by 26 publications

(13 citation statements)

References 43 publications

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“…The anticancer effects of different treatment groups were investigated by MTT assay as previously described. 32 BEL7402 cells alone and BEL7402/HUVEC co-cultured cells (ratio of BEL7402 to HUVEC cells was 5:1) were seeded in 96-well plates at a density of 6×10 3 cells/well and then cultured for 24 hours at 37 °C, respectively. After the medium was replaced with free CUR solution, free CA4P solution, mixture of CUR and CA4P, CUCA/Lip, CUCA/Gal-Lip, CUCA/GA&Gal-Lip, respectively, these cells were incubated for 48 h. Subsequently,10 μL of MTT (5mg/mL) was added to the 96-well plate for further incubation.…”

Section: Methodsmentioning

confidence: 99%

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

Wang¹,

Li²,

Jiang³

et al. 2021

IJN

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Background Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. Methods Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel “BEL-7402+HUVEC” co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. Results The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. Conclusion CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.

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Section: Methodsmentioning

confidence: 99%

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

Wang¹,

Li²,

Jiang³

et al. 2021

IJN

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“…DLS measurements were carried out in an aqueous solution, giving a smaller size than that obtained from the AFM images. The unimolecular micelles had a size in a range between 30 and 75 nm, appropriate as drug carriers, as the requirement is neither below 10 nm nor above 100 nm. − A smaller particle size is preferable, according to a study indicating that the efficiency of drug carrier particles is boosted by decreasing their size …”

Section: Resultsmentioning

confidence: 99%

“…55−57 A smaller particle size is preferable, according to a study indicating that the efficiency of drug carrier particles is boosted by decreasing their size. 58 The DLS measurement showed a decreased size in the randomly grafted and end-grafted unimolecular micelles of higher generations; the RGD-PSar-g-G1 micelles are smaller than their RGD-PSar-g-G0 counterparts, for example. The higher density of the polypeptide hydrophobic core causes that phenomenon since the core tends to shrink in the aqueous solution.…”

Section: ■ Materials and Instrumentationmentioning

confidence: 95%

Hybrid Arborescent Polypeptide-Based Unimolecular Micelles: Synthesis, Characterization, and Drug Encapsulation

2022

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This paper reports novel hybrid arborescent polypeptides based on poly(γ-benzyl l-glutamate)-co-poly(γ-tert-butyl l-glutamate)-g-polysarcosine [P(BG-co-Glu(OtBu))-g-PSar]. The synthesis is launched by ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl l-glutamate (BG-NCA) and γ-tert-butyl l-glutamate (Glu(OtBu)-NCA) to synthesize a random copolymer P(BG-co-Glu(OtBu)) serving as a precursor for the arborescent system, followed by deprotection of the tert-butyl (tBu) groups to afford free COOH moieties serving as coupling sites. Two copolymerization reactions were carried out to afford the side chains. One type of side chain was a random copolymer P(BG-co-Glu(OtBu)), while the other type was a triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu). The peptide coupling reactions were conducted between the COOH moieties on the precursor and the terminus amine on the chain end of the P(BG-co-Glu(OtBu)) random copolymer or the PGlu(OtBu)-b-PBG-b-PGlu(OtBu) triblock copolymer to obtain G0 polymers. Afterward, hydrolyzing the tBu moieties of the G0 substrates yielded randomly functionalized G0 and end-functionalized G0. Randomly functionalized G0 was used as a substrate for the next generation G1 (randomly functionalized and end-functionalized G1 after deprotection) or coated with polysarcosine (PSar) to gain G0-g-PSar. The G0 substrate prepared with the triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu) was only grafted with PSar after deprotection, resulting in G0-eg-PSar. Depending on the functionality mode of the G1 substrate, the PSar coating yielded two different graft polymers, G1-g-PSar and G1-eg-PSar, for randomly functionalized and end-functionalized G1, respectively. The PSar hydrophilic shell was decorated with the sequence of (arginine, glycine, and aspartic acid) tripeptides (RGD) as a targeting ligand to improve the potentiality of the arborescent unimolecular micelles as drug carriers. Preparative size exclusion chromatography (SEC) was used to fractionate these complex macromolecular architectures. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Raman spectroscopy, and SEC were used for molecular characterization of all intermediate and final products and dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) for micellar characterization. A comparison between randomly grafted (g) and end-grafted (eg) unimolecular micelles demonstrates that the former has an undefined core–shell structure, unlike its end-grafted analog. In addition, this study has proved that decoration of the shell with RGD contributed to avoiding micelle aggregation but limited chemotherapy agent encapsulation. However, more than their naked analog, the sustained release was noticeable in decorated micelles. Doxorubicin was utilized as a chemotherapy model, and loading was achieved successfully by physical entrapment.

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“…DGNs were prepared by ethanol injection method . First, GAH was dissolved in PBS, and the pH value was adjusted to 5.5–6.0 using sodium hydroxide solution.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Response of Multifunctional Lipid and Micelle Formulation in Hepatocellular Carcinoma

Wang

Dong

et al. 2022

ACS Appl. Mater. Interfaces

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Hepatic stellate cells (HSCs), as an important part of the tumor microenvironment (TME), could be activated by tumor cells as cancer-associated fibroblasts (CAFs), thereby promoting the production of extracellular matrix (ECM) and favoring the development of tumors. Therefore, blocking the "CAFs-ECM" axis is a promising pathway to improve antitumor efficacy. Based on this, we developed a multifunctional nanosized delivery system composed of hyaluronic acid-modified pHsensitive liposomes (CTHLs) and glycyrrheic acid-modified nanomicelles (DGNs), which combines the advantages of targeted delivery, pH-sensitivity, and deep drug penetration. To mimic actual TME, a novel HSCs+BEL-7402 cocultured cell model and a m-HSCs+H22 coimplanted mice model were established. As expected, CTHLs and DGNs could target CAFs and tumor cells, respectively, and promote the drug penetration and retention in tumor regions. Notably, CTHLs+DGNs not only exhibited a superior antitumor effect in three-level tumor-bearing mice but also presented excellent antimetastasis efficiency in lung-metastatic mice. The antitumor mechanism revealed that the lipid&micelle mixed formulations effectively inhibited the activation of CAFs, reduced the deposition of ECM, and reversed the epithelialmesenchymal transition (EMT) of tumor cells. In brief, the nanosized delivery system composed of CTHLs and DGNs could effectively improve the therapeutic effect of liver cancer by blocking the "CAFs-ECM" axis, which has a good clinical application prospect.

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Study on different particle sizes of DOX-loaded mixed micelles for cancer therapy

Cited by 26 publications

References 43 publications

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

Hybrid Arborescent Polypeptide-Based Unimolecular Micelles: Synthesis, Characterization, and Drug Encapsulation

Therapeutic Response of Multifunctional Lipid and Micelle Formulation in Hepatocellular Carcinoma

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