Abstract：
:Effective penetration of drug-carrying nanoparticles into solid tumors is a major challenge in cancer therapy. Exploration of the physicochemical properties of nanoparticles that affect penetration efficiency is required to achieve maximum therapeutic effects. Here, we used confocal laser scanning microscopy to evaluate the efficiencies of penetration of fluorescently labeled liposomes into three-dimensional spheroids composed of HeLa cells. The prepared liposomes were composed of phosphatidylcholines and varying contents of cholesterol and/or a polyethylene glycol-modified phospholipid. We demonstrated that the efficiency of penetration into spheroids increased with the bending modulus (i.e., membrane rigidity) of the liposome, as determined by atomic force microscopy (correlation coefficient, 0.84). To clarify the mechanism by which membrane rigidity contributes to the penetration behavior of liposomes, we also analyzed the cellular uptake using monolayer cells. We showed that penetration efficiency was explained partially by cellular uptake efficiency, but that other factors such as liposome diffusion efficiency in the intercellular space of tumor spheroids contributed. Our results quantitatively demonstrate that the bending modulus of the liposomal membrane is a major determinant of liposomal penetration into three-dimensional spheroids. The present study will contribute to the understanding and control of tumor penetration of liposomal formulations.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Takechi-Haraya Y,Goda Y,Sakai-Kato Kdoi
10.1021/acs.molpharmaceut.7b00051subject
Has Abstractpub_date
2017-06-05 00:00:00pages
2158-2165issue
6eissn
1543-8384issn
1543-8392journal_volume
14pub_type
杂志文章abstract：:It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX)....
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b00717
更新日期：2018-11-05 00:00:00
abstract：:The Biopharmaceutical Classification System (BCS), which is a scientific approach to categorize active drug ingredient based on its solubility and intestinal permeability into one of the four classes, has been used to set the pharmaceutical quality standards for drug products in western society. However, it has receiv...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300502m
更新日期：2013-05-06 00:00:00
abstract：:The applicability of the computational docking approach was investigated to create a novel method for quick additive screening to inhibit the crystallization taking place in amorphous drugs. Surface energy and attachment energy were utilized to recognize the morphologically most important crystal faces. The surfaces (...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300135h
更新日期：2012-10-01 00:00:00
abstract：:Cyclic RGD (cRGD) peptide-conjugated boronated albumin was developed to direct toward integrin αvβ3, which overexpresses on many cancer cells. A stepwise conjugation of c[RGDfK(Mal)] and maleimide-conjugated closo-dodecaborate (MID) to bovine serum albumin (BSA) afforded cRGD-MID-BSA, which was noncytotoxic toward bot...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00478
更新日期：2020-10-05 00:00:00
abstract：:Some of the most significant therapeutic leads and agents used for the treatment of cancer target microtubule dynamics. Paclitaxel is an exceptional example that is currently used for treating a wide range of tumors. New, non-taxane microtubule stabilizers, including several epothilones, are advancing through clinical...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp060016h
更新日期：2006-07-01 00:00:00
abstract：:The melanocortin 1 receptor (MC1R) is overexpressed in most melanoma metastases, making it a promising target for imaging of melanomas. In this study, the expression of MC1R in a large fraction of patients with melanoma was confirmed using mRNA and tissue microarray. Here, we have characterized the in vivo tumor and t...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400222j
更新日期：2013-08-05 00:00:00
abstract：:Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b01064
更新日期：2018-04-02 00:00:00
abstract：:Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a rece...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200122w
更新日期：2011-06-06 00:00:00
abstract：:Fenretinide, a chemotherapeutic agent for cancer, is water-insoluble and has a very low oral bioavailability. Hence, the objective was to deliver it as an injectable depot and improve the drug solubility and release behavior from poly(lactide-co-glycolide) (PLGA) microspheres by incorporating nonionic surfactants with...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00961
更新日期：2016-08-01 00:00:00
abstract：:Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a criti...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp100050d
更新日期：2010-08-02 00:00:00
abstract：:Gemcitabine, a clinically effective nucleoside anticancer agent, is a polar drug with low membrane permeability and is administered intravenously. Further, extensive degradation of gemcitabine by cytidine deaminase to an inactive metabolite in the liver affects its activity adversely. Thus, strategies that provide bot...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp049888e
更新日期：2005-03-01 00:00:00
abstract：:Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the e...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300496x
更新日期：2013-01-07 00:00:00
abstract：:Cancer is a leading cause of death within developed nations, and part of this morbidity is due to difficulties associated with its treatment. Currently, anticancer therapy relies heavily upon the administration of small molecule cytotoxic drugs that attack both cancerous and noncancerous cells due to limited selectivi...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章,评审
doi：10.1021/mp2005966
更新日期：2012-03-05 00:00:00
abstract：:The human organic anion-transporting polypeptides OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3) are liver-enriched membrane transporters of major importance to hepatic uptake of numerous endogenous compounds, including bile acids, steroid conjugates, hormones, and drugs, including the 3-hydroxy-3-methylglutaryl Co-A reducta...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200629s
更新日期：2012-04-02 00:00:00
abstract：:An ability to estimate the maximum flux of a xenobiotic across skin is desirable from the perspective of both drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This artic...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300146m
更新日期：2012-07-02 00:00:00
abstract：:Three different types of atom accessibility descriptors are investigated in relation to site of metabolism predictions. To enable the integration of local accessibility we have constructed 2DSASA, a method for the calculation of the atomic solvent accessible surface area that is independent of 3D coordinates. The meth...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3005116
更新日期：2013-04-01 00:00:00
abstract：:Polymer therapeutics have shown promise as tumor-targeted drug delivery systems in mice. The multivalency of polymers allows the attachment of different functional agents to a polymeric backbone, including chemotherapeutic and antiangiogenic drugs, as well as targeting moieties, such as the bone-targeting agent alendr...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp200083n
更新日期：2011-08-01 00:00:00
abstract：:Cationic poly-L-lysine 3H-dendrimers with either 16 or 32 surface amine groups (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation 3 and 4, respectively) have been synthesized and their pharmacokinetics and biodistribution investigated after intravenous administration to rats. The species...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp060032e
更新日期：2006-09-01 00:00:00
abstract：:Alkylphosphocholine (APC) analogs are a novel class of broad-spectrum tumor-targeting agents that can be used for both diagnosis and treatment of cancer. The potential for clinical translation for APC analogs will strongly depend on their pharmacokinetic (PK) profiles. The aim of this work was to understand how the ch...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b01301
更新日期：2019-08-05 00:00:00
abstract：:The objective of this study is to synthesize and evaluate acute toxicity of the bacterial cellulose (BC)/acrylamide (Am) hydrogels as noncytotoxic and biocompatible oral drug delivery vehicles. A novel series of solubilized BC/Am hydrogels were synthesized using a microwave irradiation method. The hydrogels were chara...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500337r
更新日期：2014-10-06 00:00:00
abstract：:Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO)...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp9001393
更新日期：2010-02-01 00:00:00
abstract：:The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobil...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00904
更新日期：2018-02-05 00:00:00
abstract：:In this work, we have developed covalent and low molecular weight docetaxel delivery systems based on conjugation with N-acetyl-d-galactosamine and studied their properties related to hepatocellular carcinoma cells. The resulting glycoconjugates have an excellent affinity to the asialoglycoprotein receptor (ASGPR) in ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00980
更新日期：2021-01-04 00:00:00
abstract：:Lipoplexes, composed of Lipofectamine and mRNA encoding HIV Gag protein, were shown to be internalized by dendritic cells (DCs) and promote antigen presentation to stimulate HIV-specific T cell responses. Using confocal microscopy, we showed that one-third of fluorescently labeled mRNA containing lipoplexes are coloca...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3003336
更新日期：2012-10-01 00:00:00
abstract：:The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional pref...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp4000794
更新日期：2013-08-05 00:00:00
abstract：:The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxi...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300193f
更新日期：2012-10-01 00:00:00
abstract：:Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release. NMR was used to measure water diffusivity in different media varying in their osmolality and viscosity. Water self-diffusion coefficients in sucrose, sodium chloride, and ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp3006209
更新日期：2013-06-03 00:00:00
abstract：:This work was designed to clarify the absolute abundances of transporters and receptors at different cerebral regions of the blood-brain barriers (BBB) and blood-spinal cord barrier (BSCB) in humans and rats, using physiologically relevant units (pmol/g tissue and fmol/cm2); 39 and 29 proteins including tight-junction...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00178
更新日期：2020-06-01 00:00:00
abstract：:The aim of the research work was to develop and characterize a concanavalin-A (Con-A) conjugated gastroretentive multiparticulate delivery system of clarithromycin (CM) for the effective treatment of colonization of Helicobacter pylori (H. pylori). Ethylcellulose (EC) microspheres containing CM were prepared using emu...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp800193n
更新日期：2009-01-01 00:00:00
abstract：:The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB, which may lead to changes in brain distribution and central nervous system side effects o...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00168
更新日期：2015-09-08 00:00:00
