Abstract：
:Antibody-coupled photosensitive molecules can achieve an ideal tumor-specific photodynamic therapy (PDT) and show strong clinical application potential. However, some inherent disadvantages, such as long circulation half-life, poor permeation into solid tumors, and difficulty in obtaining uniform coupling products, present potential problems to clinical applications. In this study, we propose a novel design of targeting photosensitizers, based on a very small targeting protein (an affibody molecule) coupled with photosensitive compounds, to address these problems. In the synthesis, photosensitive pyropheophorbide-a (Pyro) is modified with a PEG linker (molecular weight of 727 Da) and then site specifically coupled to the anti-HER2 ZHER2:2891 affibody protein to provide a homogeneous protein-coupled photosensitizer via a convenient process. In vitro and in vivo experiments show that this molecule has an ideal selectivity for binding and photocytotoxicity against HER2-positive cells (more than 50-fold selectivity between HER2-high expression and HER2-low expression cells) and highly specific tumor accumulation; at a relatively low dose, it effectively eliminated HER2-high expression NCI-N87 tumors in a mouse model. It is worth noting that Pyro only has a moderate photodynamic activity; however, the affibody-coupled Pyro molecule (Pyro-Linker-ZHER2) still shows excellent tumor therapeutic function. The more ideal tumor permeability of small ligands may be helpful to enhance the drug concentration in the tumor site and the ability to penetrate deeply inside the tumor. Coupling photosensitive compounds with affibody proteins may provide a new way for targeting PDT of tumors.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Li S,Jin Y,Su Y,Li W,Xing Y,Wang F,Hong Zdoi
10.1021/acs.molpharmaceut.9b01247subject
Has Abstractpub_date
2020-05-04 00:00:00pages
1546-1557issue
5eissn
1543-8384issn
1543-8392journal_volume
17pub_type
杂志文章abstract：:Hyperbilirubinemia may arise due to inadequate clearance of bilirubin from the body. Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. Once in the hepatocytes, it is extensively glucuronidated by UGT1A1. Eventually, the glucuronid...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp4001348
更新日期：2013-08-05 00:00:00
abstract：:We report the development of sponge Haliclona sp. spicules, referred to as SHS, and its topical application in skin delivery of hydrophilic biomacromolecules, a series of fluorescein isothiocyanate-dextrans (FDs). SHS are silicious oxeas which are sharp-edged and rod-shaped (∼120 μm in length and ∼7 μm in diameter). S...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00468
更新日期：2017-09-05 00:00:00
abstract：:This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the foca...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp100260c
更新日期：2011-04-04 00:00:00
abstract：:In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation fo...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00069
更新日期：2019-05-06 00:00:00
abstract：:We present an in situ hydrophobic salt forming technique for the encapsulation of weakly hydrophobic, ionizable active pharmaceutical ingredients (API) into stable nanocarriers (NCs) formed via a rapid precipitation process. Traditionally, NC formation via rapid precipitation has been difficult with APIs in this class...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp300452g
更新日期：2013-01-07 00:00:00
abstract：:Dendrimers are being explored in many preclinical studies as drug, gene, and imaging agent delivery systems. Understanding their detailed organ, tissue, cellular uptake, and retention can provide valuable insights into their effectiveness as delivery vehicles and the associated toxicity. This work explores a fluoresce...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400371r
更新日期：2013-12-02 00:00:00
abstract：:Nucleic acid biopharmaceuticals are being investigated as potential therapeutics. They need to be incorporated into a biocompatible carrier so as to overcome several biological barriers. Rational development of suitable nanocarriers requires high-quality characterization techniques. While size, concentration, and stab...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00999
更新日期：2018-03-05 00:00:00
abstract：:2-Methoxyestradiol (2MeO-E2) is an endogenous metabolite of estrogen which was initially considered to be inactive. During the last few decades it has been shown that 2MeO-E2 is a promising anticancer drug. In vitro experiments have demonstrated that it has several anticancer activities, and potential to alleviate hyp...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章,评审
doi：10.1021/mp100190f
更新日期：2010-12-06 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：:The molecular mechanisms of autophagy in polyethylenimine (PEI)-treated cells are not well understood because of the use of nonspecific autophagy inhibitors. Here, we applied autophagy-related gene expression analysis to pinpoint the molecular mechanisms of autophagy in PEI-treated wild-type and atg5 gene knockout (at...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500111u
更新日期：2014-09-02 00:00:00
abstract：:As microRNAs (miRNAs) have been reported to be a type of novel high-value small molecule (SM) drug targets for disease treatments, many researchers are engaged in the field of exploring new SM-miRNA associations. Nevertheless, because of the high cost, adopting traditional biological experiments constrains the efficie...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00384
更新日期：2019-07-01 00:00:00
abstract：:Photodynamic therapy, a procedure that uses a photosensitizer to enable light therapy selectively at diseased sites, remains underutilized in oncological clinic. To further improve its cancer selectivity, we developed a polymeric nanosystem by conjugating a photosensitizer IRDye 700DX (IR700) and cancer targeting RGD ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.8b00088
更新日期：2018-07-02 00:00:00
abstract：:Lipid-based drug delivery systems have been vastly investigated as a pharmaceutical method to enhance oral absorption of lipophilic drugs. However, these vehicles not only affect drug bioavailability but may also have an impact on gastric emptying, drug disposition, lymphatic absorption and be affected by lipid digest...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00141
更新日期：2020-06-01 00:00:00
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 evalua...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00051
更新日期：2017-06-05 00:00:00
abstract：:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicella...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500389v
更新日期：2014-11-03 00:00:00
abstract：:Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.0c00937
更新日期：2021-01-11 00:00:00
abstract：:The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid o...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp500242q
更新日期：2014-10-06 00:00:00
abstract：:Polymeric nanoparticles (NPs) are extremely attractive vaccine adjuvants, able to promote antigen delivery and in some instances, exert intrinsic immunostimulatory properties that enhance antigen specific humoral and cellular immune responses. The poly-ε-caprolactone (PCL)/chitosan NPs were designed with the aim of be...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00730
更新日期：2018-01-02 00:00:00
abstract：:Current experimental methodologies used to determine the thermodynamic solubility of an API within a polymer typically involves establishing the dissolution/melting end point of the crystalline API within a physical mixture or through the use of the glass transition temperature measurement of a demixed amorphous solid...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00445
更新日期：2018-04-02 00:00:00
abstract：:Powder adhesion or sticking onto punches is one of the outstanding issues in pharmaceutical tablet manufacturing. We show in this work that, at comparable particle sizes, the acesulfame potassium exhibited pronouncedly reduced propensity to punch sticking than acesulfame. Detailed analyses revealed strong correlation ...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00247
更新日期：2019-06-03 00:00:00
abstract：:In this study, dinitrosyl iron complexes (DNICs) are shown to deliver nitric oxide (NO) into the cytosol of vascular smooth muscle cells (SMCs), which play a major role in vascular relaxation and contraction. Malfunction of SMCs can lead to hypertension, asthma, and erectile dysfunction, among other disorders. For com...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00389
更新日期：2019-07-01 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：:To predict the outcome of intestinal drug transporter induction on pharmacokinetics, signaling of the DNA message along with messenger RNA (mRNA) transcription and protein translation leading to transporter function must be understood. We quantified the gene expression of PXR and CAR, gene expression and protein abund...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00458
更新日期：2019-09-03 00:00:00
abstract：:Currently, the most prominent barrier to the success of orally delivered paclitaxel (PTX) is the extremely limited bioavailability of delivered therapeutic. In light of this issue, an amphiphilic sulfhydrylated N-deoxycholic acid-N,O-hydroxyethyl chitosan (TGA-DHC) was synthesized to improve the oral bioavailability o...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00662
更新日期：2017-12-04 00:00:00
abstract：:Whether luteolin inhibits HBV replication has not been validated and the underlying mechanism of which has never been elucidated. In this study, we show that luteolin reduces HBV DNA replication in HepG2.2.15 cells. Luteolin effectively inhibited the expression of hepatocyte nuclear factor 4α (HNF4α) and its binding t...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.5b00789
更新日期：2016-02-01 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：:RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via an RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as li...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/mp400541z
更新日期：2014-03-03 00:00:00
abstract：:In vitro antibody discovery and/or affinity maturation are often performed using antibody fragments (Fabs), but most monovalent Fabs are reformatted as bivalent IgGs (monoclonal antibodies, mAbs) for therapeutic applications. One problem related to reformatting antibodies is that the bivalency of mAbs can lead to incr...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.7b00779
更新日期：2018-01-02 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：:The small molecule fluorescein is commonly used to guide the repair of cerebral spinal fluid leaks (CSFLs) in the clinic. We modified fluorescein so that it is also visible by positron emission tomography (PET). This probe was used to quantitatively track the fast distribution of small molecules in the CSF of rats. We...
journal_title：Molecular pharmaceutics
pub_type： 杂志文章
doi：10.1021/acs.molpharmaceut.9b00485
更新日期：2019-08-05 00:00:00
