Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells

Lee, Seulgi; Song, Su Jeong; Lee, Jeil; Ha, Tai Hwan; Choi, Joon Sig

doi:10.3390/pharmaceutics12090876

Cited by 33 publications

(14 citation statements)

References 28 publications

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“… Enzyme-responsive drug release from doxorubicin loaded PEG lipid-GLFG peptide liposome designed as a cathepsin B cleavable peptide linker to hydrolyse and release drugs specifically in tumour cells (reproduced from [ 151 ] with permission from Polymers , MDPI licensed under Creative Commons Attribution (CC BY 4.0) license). …”

Section: Figurementioning

confidence: 99%

“…In this study, the anticancer drug doxorubicin was loaded into cathepsin B responsive liposomes made of PEG lipid GLFG-peptide linker. The liposomes are uptaken by endocytosis; in the presence of tumour-specific enzymes (cathepsin MMP2/9) and low pH of tumour cell, the lipids get hydrolysed and release the drug [151]. This helps in triggering the drug release by the external illumination of light.…”

Section: Enzyme Responsivementioning

confidence: 99%

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Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.

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Section: Figurementioning

confidence: 99%

Section: Enzyme Responsivementioning

confidence: 99%

Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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“…The drug-loaded micelles were transported into the lysosomes and taken into the cells by phagocytosis. Then, the dendritic Phe-Lys dipeptides were degraded by cathepsin B at relatively high concentrations in the lysosomes, 37 resulting in the slow and continual release of DOX, which was also demonstrated in the in vitro release experiments. Thus, DOX fluorescence was mainly localized in the cytoplasm of the cells, and less fluorescence was distributed in the cell nucleus.…”

Section: In Vitro Dox Release Studiesmentioning

confidence: 66%

Cathepsin B and thermal dual‐stimuli responsive linear‐dendritic block copolymer micelles for anticancer drug delivery

Song

Wei

et al. 2021

Polymer International

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In this study, two linear poly(N-vinylcaprolactam)s (PNVCLs) with different molecular weights were first synthesized as polymeric supporters by reversible addition-fragmentation chain transfer polymerization and then were used to prepare cathepsin B and thermal dual-stimuli responsive amphiphilic linear-dendritic block copolymers (LDBCs) PNVCL n -b-D(Phe-Lys) 1-3 (n = 66, 100) with linear PNVCL and dendritic phenylalanyl-lysine (Phe-Lys) dipeptides via stepwise peptide chemistry. The copolymers were characterized by 1 H NMR spectra and gel permeation chromatography and exhibited a controlled molecular weight and a narrow molecular weight distribution (polydispersity index ≤ 1.27). They self-assemble into stable micelles at relatively low critical micelle concentrations (0.007-0.019 mg mL −1 ) in aqueous solution. These micelles are capable of dissociating to release the encapsulated anticancer drug doxorubicin upon cathepsin B treatment. The doxorubicin release rates from PNVCL n -b-D (Phe-Lys) 1-3 micelles decreased with increasing generation of Phe-Lys dipeptide dendrons and decreasing molecular weight of PNVCL. In addition, the lower critical solution temperatures of the copolymers increased with an extension of the enzyme incubation time. The results of in vitro cytotoxicity and cell uptake experiments showed that LDBCs show no cytotoxicity even at a high LDBC concentration of 0.4 mg mL −1 and the drug-loaded micelles can be enriched in tumor cells. Such smart copolymers could be efficiently used in targeted therapy systems.

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“…Lee et al synthesized PEG-Gly-Leu-Phe-Gly (GLFG) using DSPE-PEG (5000) amine, DPPC, and (2,3-dioleoyloxy-propyl)-trimethylammonium-chloride (DOTAP) as lipid materials after PEG modification. 60 Adriamycin-loaded GLFG liposomes were further prepared. These liposomes are degraded by cathepsin B enzyme, which is overexpressed in several cancer cell types and exhibits an effective anticancer effect on HepG2 cells in vitro and inhibits cancer cell proliferation in a zebrafish model.…”

Section: Lipid-based Nanoemulsionsmentioning

confidence: 99%

Lipid-Based Nanocarrier Systems for Drug Delivery: Advances and Applications

Zhao

Zhou

et al. 2022

Pharmaceutical Fronts

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Lipid-based nanocarriers have been extensively investigated for drug delivery due to their advantages including biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. However, the shortcomings of traditional lipid-based nanocarriers such as insufficient targeting, capture by the reticuloendothelial system, and fast elimination limit the efficiency of drug delivery and therapeutic efficacy. Therefore, a series of multifunctional lipid-based nanocarriers have been developed to enhance the accumulation of drugs in the lesion site, aiming for improved diagnosis and treatment of various diseases. In this review, we summarized the advances and applications of lipid-based nanocarriers from traditional to novel functional lipid preparations, including liposomes, stimuli-responsive lipid-based nanocarriers, ionizable lipid nanoparticles, lipid hybrid nanocarriers, as well as biomembrane-camouflaged nanoparticles, and further discussed the challenges and prospects of this system. This exploration may give a complete idea viewing the lipid-based nanocarriers as a promising choice for drug delivery system, and fuel the advancement of pharmaceutical products by materials innovation and nanotechnology.

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Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells

Cited by 33 publications

References 28 publications

Controlled Drug Delivery Systems: Current Status and Future Directions

Controlled Drug Delivery Systems: Current Status and Future Directions

Cathepsin B and thermal dual‐stimuli responsive linear‐dendritic block copolymer micelles for anticancer drug delivery

Lipid-Based Nanocarrier Systems for Drug Delivery: Advances and Applications

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