- Tailor-Made pH-Responsive Poly(choline phosphate) Prodrug as a Drug Delivery System for Rapid Cellular Internalization
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Rapid cellular uptake and efficient drug release in tumor cells are two of the major challenges for cancer therapy. Herein, we designed and synthesized a novel pH-responsive polymer-drug conjugate system poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-methoxy-2-oxoethyl methacrylate-hydrazide-doxorubicin) (PCP-Dox) to overcome these two challenges simultaneously. It has been proved that PCP-Dox can be easily and rapidly internalized by various cancer cells due to the strong interaction between multivalent choline phosphate (CP) groups and cell membranes. Furthermore, Dox, linked to the polymer carrier via acid-labile hydrazone bond, can be released from carriers due to the increased acidity in lysosome/endosome (pH 5.0-5.5) after the polymer prodrug was internalized into the cancer cells. The cell viability assay demonstrated that this novel polymer prodrug has shown enhanced cytotoxicity in various cancer cells, indicating its great potential as a new drug delivery system for cancer therapy.
- Wang, Wenliang,Wang, Bo,Ma, Xiaojing,Liu, Sanrong,Shang, Xudong,Yu, Xifei
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- Acid-Activatable Theranostic Unimolecular Micelles Composed of Amphiphilic Star-like Polymeric Prodrug with High Drug Loading for Enhanced Cancer Therapy
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Stimuli-responsive nanomedicine with theranostic functionalities with reduced side-effects has attracted growing attention, although there are some major obstacles to overcome before clinical applications. Herein, we present an acid-activatable theranostic unimolecular micelles based on amphiphilic star-like polymeric prodrug to systematically address typical existing issues. This smart polymeric prodrug has a preferable size of about 35 nm and strong micellar stability in aqueous solution, which is beneficial to long-term blood circulation and efficient extravasation from tumoral vessels. Remarkably, the polymeric prodrug has a high drug loading rate up to 53.1 wt%, which induces considerably higher cytotoxicity against tumor cells (HeLa cells and MCF-7 cells) than normal cells (HUVEC cells) suggesting a spontaneous tumor-specific targeting capability. Moreover, the polymeric prodrug can serve as a fluorescent nanoprobe activated by the acidic microenvironment in tumor cells, which can be used as a promising platform for tumor diagnosis. The superior antitumor effect in this in vitro study demonstrates the potential of this prodrug as a promising platform for drug delivery and cancer therapy.
- Shi, Xiaoxiao,Hou, Meili,Bai, Shuang,Ma, Xiaoqian,Gao, Yong-E,Xiao, Bo,Xue, Peng,Kang, Yuejun,Xu, Zhigang,Li, Chang Ming
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- Diester structure monomer, preparation method thereof and application
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The invention provides a diester structure monomer, a preparation method thereof and application of an ArF photoresist formula. The preparation method of the diester structure monomer comprises the following steps of: dissolving glycolate in a reaction solvent to prepare a glycolate solution; mixing the glycolate solution with triethylamine in a protective atmosphere, and performing cooling to form a mixed solution; and keeping the protective atmosphere unchanged, and adding methacryloyl chloride into the mixed solution to carry out esterification reaction, thereby generating the diester structure monomer. According to the preparation method of the diester structure monomer, the generated diester structure monomer has a diester long side chain and a group with small size and high acid sensitivity; resin synthesized by the diester structure monomer is endowed with better adhesive force and film-forming property, deprotection reaction efficiency and plasticity, and the hardness and brittleness of the resin are improved. And the prepared diester acid protection structure monomer has the advantages of higher yield, low by-product content and easiness in separation and purification.
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Paragraph 0063-0070
(2021/02/10)
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- In response to the pH of such amphiphilic rod-like adriamycin polymer prodrugs of preparation method
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The invention relates to the fields of chemical synthesis and biological representation, and more particularly, provides a preparation method and an application of a pH-responsive amphiphilic rod-likepolymer prodrug, which is represented as the drawing in the specification. The preparation method of the amphiphilic rod-like polymer material includes the following steps: 1) synthesizing a rod-likeATRP initiator on the basis of glucan; 2) introducing a pH-responsive hydrophobic block on the basis of ATRP reaction; 3) introducing a hydrophilic block on the basis of ATRP reaction to obtain an amphiphilic polymer material; 4) substituting an ester group on the terminal of MGMA by means of hydrazine hydrate, thus producing a pH-responsive precursor; 5) forming a hydrazone bond by means of a carbonyl group on adriamycin and an amino group on the polymer material, thus producing the pH-responsive polymer prodrug. By means of weak acidity of interior of cancer cells, the amphiphilic rod-likepolymer prodrug can selectively release a drug by means of pH-stimulating response. The polymer prodrug is high in micelle stability, is high in drug carrying capacity and enables drug release to be under stimulating response control.
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Paragraph 0034; 0040; 0042
(2019/11/13)
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- Method for preparing amphipathy star-like doxorubicin polymer prodrug
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The invention relates to the field of medicinal chemistry synthesis, in particular to a preparation method and application of an amphipathy star-like doxorubicin polymer prodrug. The preparation method of the amphipathy star-like doxorubicin polymer prodrug comprises the following steps: (1) synthesizing a star-like ATRP (Atom Transfer Radical Polymerization) initiator on the basis of cyclodextrin; (2) introducing a hydrophobic monomer with pH sensitivity through ATRP reaction; (3) introducing hydrophilic ethylene glycol methacrylate (OEGMA) through the ATRP reaction so as to obtain a star-like amphipathy polymer prodrug; (4) substituting an ester group at the tail end of MGMA by using amino of hydrazine hydrate; (5) further modifying doxorubicin by using amino on a polymer. The amphipathy star-like doxorubicin polymer prodrug has the advantages of being high in micelle stability, high in drug loading capacity, good in stimulation response control and the like, and the characteristics that water solubility of hydrophobic drug molecules and transferring of nano medicines are effectively solved.
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Paragraph 0025
(2017/08/31)
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- POLYMERS INCLUDING ACTIVE AGENTS
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Polymers are described herein comprising: a reaction product of a prepolymer solution including at least one macromer and at least one visualization agent; and an active agent electrostatically bound to the polymer filament or chemically bound to the at least one monomer; wherein the polymer filament does not include metallic support members.
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- Polymerizable compound, lactone-containing compound, method for manufacturing lactone-containing compound and polymer compound obtained by polymerizing the polymerizable compound
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A polymerizable compound having a lactone structure represented by formula (1) is provided: wherein A represents a polymerizable site; R2 represents a single bond or an alkylene group; R3 represents a hydrocarbon group in which hydrogen atoms are substituted with a fluorine atom; R4 represents a halogen atom, a cyano group, a hydroxyl group, an amide group, an alkyl group, a cycloalkyl group, an alkoxy group, a phenol group, an acyl group, an alkoxycarbonyl group, or a group represented by R-C(=O)- or R-C(=O)O-, wherein R represents an alkyl group or a cycloalkyl group; X represents an alkylene group, an oxygen atom or a sulfur atom; Z represents a single bond, an ether bond, an ester bond, an amide bond, a urethane bond or urea bond; n represents an integer of from 0 to 5; and m represents an integer of from 0 to 7.
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Page/Page column 19
(2010/07/03)
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