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Fulltext Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus

Verma DK, Gupta D, Lal SK

Viruses, 2018 11 18;10(11).
PMID: 30453689 DOI: 10.3390/v10110650

Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.

Matched MeSH terms: Endocytosis*
DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

Setyawati MI, Kutty RV, Leong DT

Small, 2016 Oct;12(40):5601-5611.
PMID: 27571230 DOI: 10.1002/smll.201601669

Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.

Matched MeSH terms: Endocytosis/drug effects
Evaluating ligand-receptor networks of TGF-beta with membrane computing

Muniyandi RC, Zin AM

Pak J Biol Sci, 2011 Dec 15;14(24):1100-8.
PMID: 22335049

Ligand-Receptor Networks of TGF-beta plays essential role in transmitting a wide range of extracellular signals that affect many cellular processes such as cell growth. However, the modeling of these networks with conventional approach such as ordinary differential equations has not taken into account, the spatial structure and stochastic behavior of processes involve in these networks. Membrane computing as the alternatives approach provides spatial structure for molecular computation in which processes are evaluated in a non-deterministic and maximally parallel way. This study is carried out to evaluate the membrane computing model of Ligand-Receptor Networks of TGF-beta with model checking approach. The results show that membrane computing model has sustained the behaviors and properties of Ligand-Receptor Networks of TGF-beta. This reinforce that membrane computing is capable in analyzing processes and behaviors in hierarchical structure of cell such as Ligand-Receptor Networks of TGF-beta better than the deterministic approach of conventional mathematical models.

Matched MeSH terms: Endocytosis/physiology
Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats

Ling SS, Yuen KH, Magosso E, Barker SA

J Pharm Pharmacol, 2009 Apr;61(4):445-9.
PMID: 19298690 DOI: 10.1211/jpp/61.04.0005

A liposome preparation that is amenable to receptor-mediated endocytosis has been developed to enhance the oral bioavailability of poorly absorbable peptidomimetic drugs by use of folic acid as the mediator of liposomal uptake.

Matched MeSH terms: Endocytosis/drug effects*
Chemosensitivity assessments of curdlan-doped smart nanocomposites containing erlotinib HCl

Bera H, Abbasi YF, Gajbhiye V, Ping LL, Salve R, Kumar P, et al.

Int J Biol Macromol, 2021 Jun 30;181:169-179.
PMID: 33775757 DOI: 10.1016/j.ijbiomac.2021.03.152

Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.

Matched MeSH terms: Endocytosis/drug effects
Fulltext RNA interference mediated inhibition of dengue virus multiplication and entry in HepG2 cells

Alhoot MA, Wang SM, Sekaran SD

PLoS One, 2012;7(3):e34060.
PMID: 22457813 DOI: 10.1371/journal.pone.0034060

Dengue virus-host cell interaction initiates when the virus binds to the attachment receptors followed by endocytic internalization of the virus particle. Successful entry into the cell is necessary for infection initiation. Currently, there is no protective vaccine or antiviral treatment for dengue infection. Targeting the viral entry pathway has become an attractive therapeutic strategy to block infection. This study aimed to investigate the effect of silencing the GRP78 and clathrin-mediated endocytosis on dengue virus entry and multiplication into HepG2 cells.

Matched MeSH terms: Endocytosis
Fulltext Computational analysis of functional SNPs in Alzheimer's disease-associated endocytosis genes

Tey HJ, Ng CH

PeerJ, 2019;7:e7667.
PMID: 31592138 DOI: 10.7717/peerj.7667

Background: From genome wide association studies on Alzheimer's disease (AD), it has been shown that many single nucleotide polymorphisms (SNPs) of genes of different pathways affect the disease risk. One of the pathways is endocytosis, and variants in these genes may affect their functions in amyloid precursor protein (APP) trafficking, amyloid-beta (Aβ) production as well as its clearance in the brain. This study uses computational methods to predict the effect of novel SNPs, including untranslated region (UTR) variants, splice site variants, synonymous SNPs (sSNPs) and non-synonymous SNPs (nsSNPs) in three endocytosis genes associated with AD, namely PICALM, SYNJ1 and SH3KBP1.
Materials and Methods: All the variants' information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.
Results: A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer's Disease Sequencing Project (ADSP), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.
Discussion: The 56 deleterious variants were predicted to affect the regulation of gene expression, or have functional impacts on these three endocytosis genes and their gene products. The deleterious variants in these genes are expected to affect their cellular function in endocytosis and may be implicated in the pathogenesis of AD as well. The biological consequences of these deleterious variants and their potential impacts on the disease risks could be further validated experimentally and may be useful for gene-disease association study.

Matched MeSH terms: Endocytosis
Fulltext Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane

Cheung TT, Ismail NAS, Moir R, Arora N, McDonald FJ, Condliffe SB

Front Physiol, 2019;10:7.
PMID: 30800070 DOI: 10.3389/fphys.2019.00007

The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway.

Matched MeSH terms: Endocytosis
Aptamers as the chaperones (Aptachaperones) of drugs-from siRNAs to DNA nanorobots

Citartan M, Kaur H, Presela R, Tang TH

Int J Pharm, 2019 Aug 15;567:118483.
PMID: 31260780 DOI: 10.1016/j.ijpharm.2019.118483

Aptamers, nucleic acid ligands that are specific against their corresponding targets are increasingly employed in a variety of applications including diagnostics and therapeutics. The specificity of the aptamers against their targets is also used as the basis for the formulation of the aptamer-based drug delivery system. In this review, we aim to provide an overview on the chaperoning roles of aptamers in acting as the cargo or load carriers, delivering contents to the targeted sites via cell surface receptors. Internalization of the aptamer-biomolecule conjugates via receptor-mediated endocytosis and the strategies to augment the rate of endocytosis are underscored. The cargos chaperoned by aptamers, ranging from siRNAs to DNA origami are illuminated. Possible impediments to the aptamer-based drug deliveries such as susceptibility to nuclease resistance, potentiality for immunogenicity activation, tumor heterogeneity are speculated and the corresponding amendment strategies to address these shortcomings are discussed. We prophesy that the future of the aptamer-based drug delivery will take a trajectory towards DNA nanorobot-based assay.

Matched MeSH terms: Endocytosis
Near-infrared activatable phthalocyanine-poly-L-glutamic acid conjugate: increased cellular uptake and light-dark toxicity ratio toward an effective photodynamic cancer therapy

Kiew LV, Cheah HY, Voon SH, Gallon E, Movellan J, Ng KH, et al.

Nanomedicine, 2017 05;13(4):1447-1458.
PMID: 28214608 DOI: 10.1016/j.nano.2017.02.002

In photodynamic therapy (PDT), the low absorptivity of photosensitizers in an aqueous environment reduces singlet oxygen generation efficiency and thereby decreases photosensitizing efficacy in biological conditions. To circumvent this problem, we designed a phthalocyanine-poly-L-glutamic acid conjugate (1-PG) made from a new phthalocyanine (Pc 1) monofunctionalized to allow adequate conjugation to PGA. The resulting 1-PG conjugate retained high absorptivity in the near-infrared (NIR) region at its λmax675nm in an aqueous environment. The 1-PG conjugate demonstrated good singlet oxygen generation efficiency, increased uptake by 4 T1 breast cancer cells via clathrin-mediated endocytosis, and enhanced photocytotoxic efficacy. The conjugate also displayed a high light-dark toxicity ratio, approximately 1.5-fold greater than zinc phthalocyanine at higher concentration (10 μM), an important feature for the reduction of dark toxicity and unwanted side effects. These results suggest that the 1-PG conjugate could be a useful alternative for deep tissue treatment with enhanced anti-cancer (PDT) efficacy.

Matched MeSH terms: Endocytosis
Autophagy and GLUT4: The missing pieces

Elhassan SAM, Candasamy M, Chan EWL, Bhattamisra SK

Diabetes Metab Syndr, 2018 Nov;12(6):1109-1116.
PMID: 29843994 DOI: 10.1016/j.dsx.2018.05.020

BACKGROUND: Autophagy is a process devoted to degrade and recycle cellular components inside mammalian cells through lysosomal system. It plays a main function in the pathophysiology of several diseases. In type 2 diabetes, works demonstrated the dual functions of autophagy in diabetes biology. Studies had approved the role of autophagy in promoting different routes for movement of integral membrane proteins to the plasma membrane. But its role in regulation of GLUT4 trafficking has not been widely observed. In normal conditions, insulin promotes GLUT4 translocation from intracellular membrane compartments to the plasma membrane, while in type 2 diabetes defects occur in this translocation.
METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.
RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.
CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.

Matched MeSH terms: Endocytosis
Advanced nanoscale carrier-based approaches to overcome biopharmaceutical issues associated with anticancer drug 'Etoposide'

Choudhury H, Maheshwari R, Pandey M, Tekade M, Gorain B, Tekade RK

Mater Sci Eng C Mater Biol Appl, 2020 Jan;106:110275.
PMID: 31753398 DOI: 10.1016/j.msec.2019.110275

Etoposide (ETS), topoisomerase-II inhibitor, is a first-line anticancer therapeutics used in diverse cancer types. However, the therapeutic potential of this molecule has mainly impeded due to its detrimental toxicity profile, unfavorable rejection by the cancer cells due to P-glycoprotein (P-gp) efflux activity, and rapid hepatic clearance through extensive metabolism by Cytochrome-P450. To increase the therapeutic potency without significant adverse effects, the implication of novel ETS-nanoformulation strategies have recommended mainly. Nanomedicine based nanoformulation approaches based on nanoparticles (NPs), dendrimers, carbon-nanotubes (CNTs), liposomes, polymeric micelles, emulsions, dendrimers, solid-lipid NPs, etc offers immense potential opportunities to improve the therapeutic potential of pharmaceutically problematic drugs. This review provides an up-to-date argument on the work done in the field of nanomedicine to resolve pharmacokinetic and pharmacodynamic issues associated with ETS. The review also expounds the progress in regards to the regulatory, patenting and clinical trials related to the innovative formulation aspects of ETS.

Matched MeSH terms: Endocytosis
5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave

Khan NR, Wong TW

Artif Cells Nanomed Biotechnol, 2018;46(sup1):568-577.
PMID: 29378453 DOI: 10.1080/21691401.2018.1431650

This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.

Matched MeSH terms: Endocytosis
Gemcitabine interacts with carbonate apatite with concomitant reduction in particle diameter and enhancement of cytotoxicity in breast cancer cells

Mozar FS, Chowdhury EH

Curr Drug Deliv, 2015;12(3):333-41.
PMID: 25600981

Substantial amount of research has been done in recent decades for the development of nanoparticle systems to selectively deliver drugs to cancer cells for concurrently enhancing and reducing anti-cancer and off-target effects, respectively. pH-sensitive carbonate apatite (CA) was originally developed for efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell lines. Recently, the CA particles were employed to deliver anti-cancer drugs, cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report on the fabrication and characterization of gemcitabine- loaded CA particles, followed by the evaluation of their roles in enhancement of cytotoxicity in two human and one murine breast cancer cell lines. HPLC was performed to measure binding efficiency of the drug to the apatite particles whereas particle size and zeta potential were evaluated to characterize drug/apatite complex. Depending on the initial doses of the drug, its bind binding affinity towards the particles varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease with an increase of the initial drug concentration. In vitro chemosensitivity assay revealed that apatite/drug nanoparticle complexes presented significantly higher cytotoxicity to breast cancer cells compared to free drugs, which could be correlated with the enhanced cellular uptake of the small size drug-loaded particles through endocytosis compared to the passive diffusion of the free drug.

Matched MeSH terms: Endocytosis
Extraintestinal pathogenic Escherichia coli (ExPEC) of human and avian origin belonging to sequence type complex 95 (STC95) portray indistinguishable virulence features

Nandanwar N, Janssen T, Kühl M, Ahmed N, Ewers C, Wieler LH

Int J Med Microbiol, 2014 Oct;304(7):835-42.
PMID: 25037925 DOI: 10.1016/j.ijmm.2014.06.009

Extraintestinal pathogenic Escherichia coli (ExPEC) strains of certain genetic lineages are frequently implicated in a wide range of diseases in humans and birds. ExPEC strains belonging to the phylogenetic lineage/sequence type complex 95 (STC95) are one such prominent lineage that is commonly isolated from extraintestinal infections such as systemic disease in poultry and urinary tract infections (UTIs), neonatal meningitis and sepsis in humans. Several epidemiological studies have indicated that ST95 strains obtained from such infections may share similar virulence genes and other genomic features. However, data on their ability to establish infections in vivo as deduced from the manifestation of similar virulence phenotypes remain elusive. In the present study, 116 STC95 ExPEC isolates comprising 55 human and 61 avian strains, possessing similar virulence gene patterns, were characterized in vitro using adhesion, invasion, biofilm formation and serum bactericidal assays. Overall, STC95 strains from both groups, namely human and birds, were equally capable of adhering to and invading the two mammalian kidney cell lines. Similarly, these strains were able to form strong biofilms in M63 medium. Furthermore, they were equally resistant to the bactericidal activity of human and avian serum. Our cumulative data reinforce the understanding that ST95 strains from poultry present a potential zoonotic risk and therefore need a One Health strategy for a successfull intervention.

Matched MeSH terms: Endocytosis
Fulltext Inhibition of dengue virus entry and multiplication into monocytes using RNA interference

Alhoot MA, Wang SM, Sekaran SD

PLoS Negl Trop Dis, 2011 Nov;5(11):e1410.
PMID: 22140591 DOI: 10.1371/journal.pntd.0001410

Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.

Matched MeSH terms: Endocytosis
Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide

Kirby BP, Pabari R, Chen CN, Al Baharna M, Walsh J, Ramtoola Z

J Pharm Pharmacol, 2013 Oct;65(10):1473-81.
PMID: 24028614 DOI: 10.1111/jphp.12125

In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse.

Matched MeSH terms: Endocytosis
Size-dependent effect of cystine/citric acid-capped confeito-like gold nanoparticles on cellular uptake and photothermal cancer therapy

Saw WS, Ujihara M, Chong WY, Voon SH, Imae T, Kiew LV, et al.

Colloids Surf B Biointerfaces, 2018 Jan 01;161:365-374.
PMID: 29101882 DOI: 10.1016/j.colsurfb.2017.10.064

Physiochemical changes, including size, are known to affect gold nanoparticle cellular internalization and treatment efficacy. Here, we report the effect of four sizes of cystine/citric acid-coated confeito-like gold nanoparticles (confeito-AuNPs) (30, 60, 80 and 100nm) on cellular uptake, intracellular localization and photothermal anticancer treatment efficiency in MDA-MB231 breast cancer cells. Cellular uptake is size dependent with the smallest size of confeito-AuNPs (30nm) having the highest cellular internalization via clathrin- and caveolae-mediated endocytosis. However, the other three sizes (60, 80 and 100nm) utilize clathrin-mediated endocytosis for cellular uptake. The intracellular localization of confeito-AuNPs is related to their endocytosis mechanism, where all sizes of confeito-AuNPs were localized highly in the lysosome and mitochondria, while confeito-AuNPs (30nm) gave the highest localization in the endoplasmic reticulum. Similarly, a size-dependent trend was also observed in in vitro photothermal treatment experiments, with the smallest confeito-AuNPs (30nm) giving the highest cell killing rate, whereas the largest size of confeito-AuNPs (100nm) displayed the lowest photothermal efficacy. Its desirable physicochemical characteristics, biocompatible nature and better photothermal efficacy will form the basis for further development of multifunctional confeito-AuNP-based nanotherapeutic applications.

Matched MeSH terms: Endocytosis
Fulltext A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery

Biabanikhankahdani R, Bayat S, Ho KL, Alitheen NBM, Tan WS

Sci Rep, 2017 Jul 13;7(1):5303.
PMID: 28706267 DOI: 10.1038/s41598-017-05525-4

pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.

Matched MeSH terms: Endocytosis
Fulltext Targeted Delivery of Cell Penetrating Peptide Virus-like Nanoparticles to Skin Cancer Cells

Gan BK, Yong CY, Ho KL, Omar AR, Alitheen NB, Tan WS

Sci Rep, 2018 05 31;8(1):8499.
PMID: 29855618 DOI: 10.1038/s41598-018-26749-y

Skin cancer or cutaneous carcinoma, is a pre-eminent global public health problem with no signs of plateauing in its incidence. As the most common treatments for skin cancer, surgical resection inevitably damages a patient's appearance, and chemotherapy has many side effects. Thus, the main aim of this study was to screen for a cell penetrating peptide (CPP) for the development of a targeting vector for skin cancer. In this study, we identified a CPP with the sequence NRPDSAQFWLHH from a phage displayed peptide library. This CPP targeted the human squamous carcinoma A431 cells through an interaction with the epidermal growth factor receptor (EGFr). Methyl-β-cyclodextrin (MβCD) and chlorpromazine hydrochloride (CPZ) inhibited the internalisation of the CPP into the A431 cells, suggesting the peptide entered the cells via clathrin-dependent endocytosis. The CPP displayed on hepatitis B virus-like nanoparticles (VLNPs) via the nanoglue successfully delivered the nanoparticles into A431 cells. The present study demonstrated that the novel CPP can serve as a ligand to target and deliver VLNPs into skin cancer cells.

Matched MeSH terms: Endocytosis

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