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1.
J Cell Sci ; 135(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34000034

RESUMO

Membrane phase separation to form micron-scale domains of lipids and proteins occurs in artificial membranes; however, a similar large-scale phase separation has not been reported in the plasma membrane of the living cells. We show here that a stable micron-scale protein-depleted region is generated in the plasma membrane of yeast mutants lacking phosphatidylserine at high temperatures. We named this region the 'void zone'. Transmembrane proteins and certain peripheral membrane proteins and phospholipids are excluded from the void zone. The void zone is rich in ergosterol, and requires ergosterol and sphingolipids for its formation. Such properties are also found in the cholesterol-enriched domains of phase-separated artificial membranes, but the void zone is a novel membrane domain that requires energy and various cellular functions for its formation. The formation of the void zone indicates that the plasma membrane in living cells has the potential to undergo phase separation with certain lipid compositions. We also found that void zones were frequently in contact with vacuoles, in which a membrane domain was also formed at the contact site.

2.
J Cell Biol ; 220(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33439214

RESUMO

The mechanism of isolation membrane formation in autophagy is receiving intensive study. We recently found that Atg9 translocates phospholipids across liposomal membranes and proposed that this functionality plays an essential role in the expansion of isolation membranes. The distribution of phosphatidylinositol 3-phosphate in both leaflets of yeast autophagosomal membranes supports this proposal, but if Atg9-mediated lipid transport is crucial, symmetrical distribution in autophagosomes should be found broadly for other phospholipids. To test this idea, we analyzed the distributions of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol 4-phosphate by freeze-fracture electron microscopy. We found that all these phospholipids are distributed with comparable densities in the two leaflets of autophagosomes and autophagic bodies. Moreover, de novo-synthesized phosphatidylcholine is incorporated into autophagosomes preferentially and shows symmetrical distribution in autophagosomes within 30 min after synthesis, whereas this symmetrical distribution is compromised in yeast expressing an Atg9 mutant. These results indicate that transbilayer phospholipid movement that is mediated by Atg9 is involved in the biogenesis of autophagosomes.

4.
Nat Struct Mol Biol ; 27(12): 1185-1193, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33106658

RESUMO

The molecular function of Atg9, the sole transmembrane protein in the autophagosome-forming machinery, remains unknown. Atg9 colocalizes with Atg2 at the expanding edge of the isolation membrane (IM), where Atg2 receives phospholipids from the endoplasmic reticulum (ER). Here we report that yeast and human Atg9 are lipid scramblases that translocate phospholipids between outer and inner leaflets of liposomes in vitro. Cryo-EM of fission yeast Atg9 reveals a homotrimer, with two connected pores forming a path between the two membrane leaflets: one pore, located at a protomer, opens laterally to the cytoplasmic leaflet; the other, at the trimer center, traverses the membrane vertically. Mutation of residues lining the pores impaired IM expansion and autophagy activity in yeast and abolished Atg9's ability to transport phospholipids between liposome leaflets. These results suggest that phospholipids delivered by Atg2 are translocated from the cytoplasmic to the luminal leaflet by Atg9, thereby driving autophagosomal membrane expansion.

5.
Gan To Kagaku Ryoho ; 47(6): 923-926, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541169

RESUMO

BACKGROUND: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients. METHODS: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined. RESULTS: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group. CONCLUSION: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.


Assuntos
Linfócitos , Neutrófilos , Nivolumabe/uso terapêutico , Neoplasias Gástricas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
6.
Semin Cell Dev Biol ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32169402

RESUMO

Lipid droplets (LDs) are not an inert storage of excessive lipids, but play various roles in cellular lipid metabolism. Autophagy involves several mechanisms for the degradation of cellular components, and is related to many aspects of lipid metabolism. LD and autophagic membranes often distribute in proximity, but their relationship is complex. LDs can be degraded by autophagy, but LDs are also generated as a result of autophagy or support the execution of autophagy. Moreover, several proteins crucial for autophagy were shown to affect different aspects of LD formation. This article aims to categorize this multifaceted and seemingly entangled LD-autophagy relationship and to discuss unresolved issues.

7.
EMBO J ; 39(2): e102586, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31802527

RESUMO

ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the molecules and mechanisms mediating micro-ER-phagy remain unknown. Here, we first show that micro-ER-phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1-Spo7 phosphatase complex and the ESCRT machinery as key components for micro-ER-phagy. Third, we demonstrate that macro- and micro-ER-phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro-ER-phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/fisiologia , Complexos Endossomais de Distribuição Requeridos para Transporte , Membranas Intracelulares/metabolismo , Microautofagia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Homeostase , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Saccharomyces cerevisiae/metabolismo
8.
Commun Biol ; 2: 422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799425

RESUMO

Expression of the vasa gene is associated with germline establishment. Therefore, identification of vasa activator(s) should provide insights into germline development. However, the genes sufficient for vasa activation remain unknown. Previously, we showed that the BTB/POZ-Zn-finger protein Mamo is necessary for vasa expression in Drosophila. Here, we show that the truncated Mamo lacking the BTB/POZ domain (MamoAF) is a potent vasa activator. Overexpression of MamoAF was sufficient to induce vasa expression in both primordial germ cells and brain. Indeed, Mamo mRNA encoding a truncated Mamo isoform, which is similar to MamoAF, was predominantly expressed in primordial germ cells. The results of our genetic and biochemical studies showed that MamoAF, together with CBP, epigenetically activates vasa expression. Furthermore, MamoAF and the germline transcriptional activator OvoB exhibited synergy in activating vasa transcription. We propose that a Mamo-mediated network of epigenetic and transcriptional regulators activates vasa expression.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila/embriologia , Drosophila/genética , Desenvolvimento Embrionário/genética , Deleção de Sequência , Fatores de Transcrição/genética , Animais , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Modelos Biológicos , Fenótipo , Fatores de Transcrição/metabolismo
9.
Proc Natl Acad Sci U S A ; 116(27): 13368-13373, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31217287

RESUMO

TMEM16K, a membrane protein carrying 10 transmembrane regions, has phospholipid scramblase activity. TMEM16K is localized to intracellular membranes, but whether it actually scrambles phospholipids inside cells has not been demonstrated, due to technical difficulties in studying intracellular lipid distributions. Here, we developed a freeze-fracture electron microscopy method that enabled us to determine the phosphatidylserine (PtdSer) distribution in the individual leaflets of cellular membranes. Using this method, we found that the endoplasmic reticulum (ER) of mammalian cells harbored abundant PtdSer in its cytoplasmic leaflet and much less in the luminal leaflet, whereas the outer and inner nuclear membranes (NMs) had equivalent amounts of PtdSer in both leaflets. The ER and NMs of budding yeast also harbored PtdSer in their cytoplasmic leaflet, but asymmetrical distribution in the ER was not observed. Treating mouse embryonic fibroblasts with the Ca2+ ionophore A23187 compromised the cytoplasmic leaflet-dominant PtdSer asymmetry in the ER and increased PtdSer in the NMs, especially in the nucleoplasmic leaflet of the inner NM. This Ca2+-induced PtdSer redistribution was not observed in TMEM16K-null fibroblasts, but was recovered in these cells by reexpressing TMEM16K. These results indicate that, similar to the plasma membrane, PtdSer in the ER of mammalian cells is predominantly localized to the cytoplasmic leaflet, and that TMEM16K directly or indirectly mediates Ca2+-dependent phospholipid scrambling in the ER.


Assuntos
Anoctaminas/metabolismo , Retículo Endoplasmático/metabolismo , Fosfatidilserinas/metabolismo , Animais , Calcimicina/farmacologia , Cálcio/metabolismo , Ionóforos de Cálcio/farmacologia , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Membranas Intracelulares/metabolismo , Camundongos , Membrana Nuclear/metabolismo
10.
Curr Opin Cell Biol ; 57: 33-39, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30423517

RESUMO

New functionalities of phosphoinositides (PIs) are being revealed continuously, and the scale of the membrane area studied is becoming smaller, from the micrometer range like the entire surface of organelles to the nanometer range as in subdomains of organelles. Concurrently, function of less abundant PIs, such as PI(3,4)P2 and PI(3,5)P2, attracts increasing attention. In accordance with the progress, finer and more accurate information on PI distribution is required. The fluorescence biosensor method utilizing PI-binding domains and/or immunolabeling with anti-PI antibodies are used for this purpose in most studies but both methods are known to have caveats. In this article, we examined how PI distribution was defined in recent studies and discussed whether methodological uncertainty has any bearing on the results.


Assuntos
Organelas/química , Fosfatidilinositóis/análise , Animais , Transporte Biológico , Técnicas Biossensoriais , Membrana Celular/química , Cílios/química , Fluorescência , Imuno-Histoquímica
11.
Biochem Soc Trans ; 46(5): 1047-1054, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30242116

RESUMO

The membrane raft has been a focus of intensive research for the past two decades. Liquid-ordered domains form in artificial liposomes containing sterol and saturated lipids, but their presence in living cell membranes has been controversial. The yeast vacuole is exceptional in that micron-sized raft-like domains form in the stationary phase and under several other conditions. The sterol content of the vacuole in the log phase is much lower than that of liposomes showing liquid-ordered domains, suggesting that sterols may need to be supplied to the vacuole for the raft-like domain formation. We will discuss how lipids and lipid domains are organized in the vacuolar membrane and examine whether evidence is strong enough to conclude that the observed micron-sized domains are rafts.


Assuntos
Lipídeos de Membrana/química , Microdomínios da Membrana/química , Saccharomyces cerevisiae/química , Esteróis/química , Vacúolos/química , Transporte Biológico , Membrana Celular/química , Colesterol/química , Lipossomos/química , Osmose , Domínios Proteicos , Estresse Fisiológico
12.
Methods Mol Biol ; 1804: 231-239, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29926412

RESUMO

Because chemical fixatives like aldehydes do not work on most lipid molecules in the membrane, small-scale lipid distribution cannot be identified by immunoelectron microscopy in cells fixed by conventional methods. Here we describe a method for physically stabilizing membranes through quick-freezing and freeze-fracture replica formation and for specifically labeling gangliosides for electron microscopy. This method enables the ultrahigh-resolution mapping of membrane lipids including gangliosides within the two-dimensional plane of membranes.


Assuntos
Gangliosídeos/química , Microscopia Imunoeletrônica/métodos , Animais , Técnicas de Cultura de Células , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Fibroblastos/metabolismo , Técnica de Fratura por Congelamento , Congelamento , Camundongos , Coloração e Rotulagem
13.
J Cell Sci ; 131(8)2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29507116

RESUMO

This paper describes a novel type of nuclear structure - nuclear lipid islets (NLIs). They are of 40-100 nm with a lipidic interior, and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] molecules comprise a significant part of their surface. Most of NLIs have RNA at the periphery. Consistent with that, RNA is required for their integrity. The NLI periphery is associated with Pol II transcription machinery, including the largest Pol II subunit, transcription factors and NM1 (also known as NMI). The PtdIns(4,5)P2-NM1 interaction is important for Pol II transcription, since NM1 knockdown reduces the Pol II transcription level, and the overexpression of wild-type NM1 [but not NM1 mutated in the PtdIns(4,5)P2-binding site] rescues the transcription. Importantly, Pol II transcription is dependent on NLI integrity, because an enzymatic reduction of the PtdIns(4,5)P2 level results in a decrease of the Pol II transcription level. Furthermore, about half of nascent transcripts localise to NLIs, and transcriptionally active transgene loci preferentially colocalise with NLIs. We hypothesize that NLIs serve as a structural platform that facilitates the formation of Pol II transcription factories, thus participating in the formation of nuclear architecture competent for transcription.


Assuntos
Núcleo Celular/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , RNA Polimerase II/metabolismo , Fatores de Transcrição/metabolismo , Humanos
14.
Acta Histochem Cytochem ; 50(5): 141-147, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29276316

RESUMO

Phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2] is a phosphoinositide that plays important roles in signal transduction, endocytosis, and cell migration among others. The intracellular distribution of PtdIns(3,4)P2 has mainly been studied by observing the distribution of GFP-tagged PtdIns(3,4)P2-binding protein domains in live cells and by labeling with anti-PtdIns(3,4)P2 antibody in fixed cell samples, but these methods only offer low spatial resolution results and may have pitfalls. In the present study, we developed an electron microscopic method to observe the PtdIns(3,4)P2 distribution using the SDS-treated freeze-fracture replica labeling method. The recombinant GST-tagged pleckstrin homology (PH) domain of TAPP1 was used as the binding probe, and its binding to PtdIns(3,4)P2 in the freeze-fracture replica was confirmed by using liposomes containing different phosphoinositides and by the lack of labeling by a mutant probe, in which one amino acid in the PH domain was substituted. The method was applied to NIH3T3 cell samples and showed that the increase of PtdIns(3,4)P2 in cells treated with hydrogen peroxide occurs in the cytoplasmic leaflet of the plasma membrane, except in the caveolar membrane. The present method can define the distribution of PtdIns(3,4)P2 at a high spatial resolution and will facilitate our understanding of the physiological function of this less studied phosphoinositide.

15.
Elife ; 62017 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-28590904

RESUMO

Niemann-Pick type C is a storage disease caused by dysfunction of NPC proteins, which transport cholesterol from the lumen of lysosomes to the limiting membrane of that compartment. Using freeze fracture electron microscopy, we show here that the yeast NPC orthologs, Ncr1p and Npc2p, are essential for formation and expansion of raft-like domains in the vacuolar (lysosome) membrane, both in stationary phase and in acute nitrogen starvation. Moreover, the expanded raft-like domains engulf lipid droplets by a microautophagic mechanism. We also found that the multivesicular body pathway plays a crucial role in microautophagy in acute nitrogen starvation by delivering sterol to the vacuole. These data show that NPC proteins promote microautophagy in stationary phase and under nitrogen starvation conditions, likely by increasing sterol in the limiting membrane of the vacuole.


Assuntos
Autofagia , Proteínas de Transporte/metabolismo , Membranas Intracelulares/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Vacúolos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Leveduras/fisiologia , Colesterol/metabolismo , Microscopia Crioeletrônica , Vacúolos/ultraestrutura , Leveduras/ultraestrutura
16.
Cytoskeleton (Hoboken) ; 73(1): 45-56, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26615802

RESUMO

The primary cilium is a hair like structure protruding from most mammalian cells. The basic design of the primary cilium consists of a nine microtubule doublet structure (the axoneme). The Inv compartment, a distinct proximal segment of the ciliary body, is defined as the region in which the Inv protein is localized. Inv gene is a responsible gene for human nephronophthisis type2 (NPHP2). Here, we show that renal cilia have a short proximal microtubule doublet region and a long distal microtubule singlet region. The length of the Inv compartment was similar to that of the microtubule doublet region, suggesting a possibility that the doublet region is the structural basis of the Inv compartment. Respiratory cilia of inv mouse mutants had ciliary rootlet malformation and showed reduced ciliary beating frequency and ciliary beating angle, which may explain recurrent bronchitis in NPHP2 patients. In multiciliated tracheal cells, most Inv proteins were retained in the basal body and did not accumulate in the Inv compartment. These results suggest that the machinery to transport and retain Inv in cilia is different between renal and tracheal cilia and that Inv may function in the basal body of tracheal cells.


Assuntos
Movimento Celular , Cílios/patologia , Rim/patologia , Mutação/genética , Traqueia/patologia , Fatores de Transcrição/fisiologia , Animais , Cílios/metabolismo , Humanos , Rim/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Microscopia de Fluorescência , Microtúbulos/metabolismo , Frações Subcelulares , Traqueia/metabolismo
17.
J Agric Food Chem ; 62(18): 4083-9, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24735060

RESUMO

Effects of sublethal levels of the photosystem-interfering herbicides atrazine (Atr) and methyl viologen (MV) on photosynthetic electron transport were investigated in Arabidopsis thaliana mutants with defects in cyclic electron transfer (CET) activity. Analysis based on chlorophyll fluorescence parameters showed that pgr5 mutant (a defect in the PGR5 pathway) was more sensitive to both Atr and MV than wild type (Wt) and pnsB3 mutant (a defect in the NDH pathway). Real-time PCR (polymerase chain reaction) analysis of transcripts indicated that Wt plants showed marked increases in transcripts in the PRG5 and NDH pathways under treatment with either Atr or MV. In contrast, Atr increased the gene transcripts in CET, but MV decreased them in pnsB3 mutant plants. Atr did not increase the transcripts, while MV down-regulated them in pgr5 mutant. Immunoblot analysis partially supported the changes in the transcripts; that is, the protein levels of PGRL1 and PGR5 were increased in pnsB3 mutant, while no protein level was increased in pgr5 mutant after the herbicide treatment. The present results suggest that cyclic electron transport is very sensitive to photosystem-interference induced by chemicals and that the PGR5 pathway is very critical for regulation. Thus, pgr5 mutants may be useful plants for monitoring photosystem-interfering herbicides.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Herbicidas/farmacologia , NAD/metabolismo , Fotossíntese/efeitos dos fármacos , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Transporte de Elétrons/efeitos dos fármacos , Complexo de Proteínas do Centro de Reação Fotossintética/genética
18.
J Control Release ; 180: 33-41, 2014 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-24524898

RESUMO

Targeted therapy for the treatment of cancers using nanoparticles (NPs) decorated with transferrin (Tf) has been relatively successful, as several such nanocarriers are currently undergoing clinical trials. However, since native Tf has a low probability of delivering its payload due to its short residence time in the cell, or low cellular association, there is room to significantly improve the potency of current systems. We pioneered the redesign of this targeting ligand by altering the ligand-metal interaction, as suggested by our mathematical model, and here we present the first study to investigate the enhanced therapeutic efficacy of NPs conjugated to our engineered oxalate Tf. Our mathematical model was first used to predict that NPs conjugated to oxalate Tf will exhibit a higher degree of cellular association compared to native Tf-conjugated NPs. Our in vitro trafficking experiments validated the model prediction, and subsequent in vitro and in vivo efficacy studies demonstrated that this increase in cellular association further translates into an enhanced ability to deliver chemotherapeutics. Our findings signify the importance of the cellular trafficking properties of targeting ligands, as they may significantly influence therapeutic potency when such ligands are conjugated to NPs. Given the early success of a number of native Tf-conjugated NPs in clinical trials, there is potential for using Tf-variant based therapeutics in systemic drug delivery applications for cancer treatment.


Assuntos
Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/metabolismo , Transferrina/metabolismo , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Ferro/metabolismo , Masculino , Camundongos , Modelos Biológicos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Ácido Oxálico/química , Ácido Oxálico/metabolismo , Transferrina/química
19.
Microscopy (Oxf) ; 62(3): 341-52, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23204307

RESUMO

When considering drug delivery, the amount of drug that can be carried at a particular time and how the drug is incorporated efficiently into cells are important parameters. Transferrin (Tf)-conjugated nanocarriers have been used for the targeted delivery of drugs to cancer cells due to the availability of receptor-mediated clathrin-dependent endocytosis. In general, however, endocytosis seems to differ according to the size and shape of carriers. Large substances are generally internalized into cells by phagocytosis. We studied the internalization mechanism of Tf-conjugated nanoparticles (diameter, 522 nm). Tf-conjugated polystyrene particles were incorporated into cells by receptor-mediated endocytosis with large clathrin-coated vesicles even though their diameter was >500 nm and despite that fact that clathrin-coated vesicles have a diameter of ≈100 nm. This finding suggests that signals for internalization generated by stimulated Tf receptors (TfRs) activate clathrin-mediated endocytosis preferentially. Whether these larger particles could deliver drugs more efficiently than smaller particles was then examined. The toxicity of larger Tf-conjugated biodegradable nanoparticles (poly(lactic-co-glycolic acid)) encapsulating doxorubicin (diameter, 216 ± 38 nm) was appreciably dependent on the number of Tf molecules conjugated on a particle and the number of TfRs expressed on the cell membrane. Larger Tf-conjugated particles delivered drugs to cancer cells expressing many TfRs more selectively than their smaller counterparts (diameter, 56 ± 9 nm) if they were decorated with an appropriate number of Tf molecules.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Vesículas Revestidas por Clatrina/metabolismo , Doxorrubicina/metabolismo , Endocitose , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Láctico , Nanopartículas , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Transferrina/metabolismo
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