46911-83-5Relevant articles and documents
Synthesis of α-Amino Acid N-Carboxyanhydrides
Laconde, Guillaume,Amblard, Muriel,Martinez, Jean
, p. 6412 - 6416 (2021/08/30)
A simple phosgene- and halogen-free method for synthesizing α-amino acid N-carboxyanhydrides (NCAs) is described. The reaction between Boc-protected α-amino acids and T3P reagent gave the corresponding NCA derivatives in good yield and purity with no detectable epimerization. The process is safe, is easy-to-operate, and does not require any specific installation. It generates nontoxic, easy to remove byproducts. It can apply to the preparation of NCAs for the on-demand on-site production of either little or large quantities.
Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing
Bhatia, Sangeeta N.,Boehnke, Natalie,Correa, Santiago,Hammond, Paula T.,Hao, Liangliang,Straehla, Joelle P.,Wang, Wade
supporting information, p. 2776 - 2783 (2020/01/22)
Layer-by-layer nanoparticles (NPs) are modular drug delivery vehicles that incorporate multiple functional materials through sequential deposition of polyelectrolytes onto charged nanoparticle cores. Herein, we combined the multicomponent features and tumor targeting capabilities of layer-by-layer assembly with functional biosensing peptides to create a new class of nanotheranostics. These NPs encapsulate a high weight percentage of siRNA while also carrying a synthetic biosensing peptide on the surface that is cleaved into a urinary reporter upon exposure to specific proteases overexpressed in the tumor microenvironment. Importantly, this biosensor reports back on a molecular signature characteristic to metastatic tumors and associated with poor prognosis, MMP9 protease overexpression. This nanotheranostic mediates noninvasive urinary-based diagnostics in mouse models of three different cancers with simultaneous gene silencing in flank and metastatic mouse models of ovarian cancer.
Block copolymer [(l-GluA-5-BE)-: B -(l-AspA-4-BE)]-based nanoflower capsules with thermosensitive morphology and pH-responsive drug release for cancer therapy
Amgoth, Chander,Chen, Shuai,Malavath, Tirupathi,Tang, Guping
supporting information, p. 9258 - 9268 (2020/11/03)
Herein, the synthesis of an amino-acid-based di-block copolymer (di-BCP) in-between an l-glutamic acid-5-benzyl ester and l-aspartic acid-4-benzyl ester [(l-GluA-5-BE)-b-(l-AspA-4-BE)] has been reported. However, the synthesis of di-BCP of [(l-GluA-5-BE)-b-(l-AspA-4-BE)] was carried out through the facile modified ring-opening polymerization (ROP) without using any surfactants and harmful chemicals. Interestingly, the synthesized [(l-GluA-5-BE)-b-(l-AspA-4-BE)] has been used to design nanoflower capsules (NFCs) with surface-functionalized nanoflakes and petals. Notably, the simple solvent propanol has been used as a dispersing medium for the di-BCP-based powder to observe morphology of NFCs. Moreover, these amino-acid-based NFCs are biocompatible, biodegradable, and bio-safe for mankind usage. Consequently, di-BCP-based NFCs show changes in morphology with different temperature conditions, i.e., at ～10 °C, ～25 °C (RT), and ～37 °C (body temperature). Furthermore, the average thickness of the surface-functionalized nanopetals has been calculated as ～324 nm (in diameter). Similarly, the average distance between petals is calculated as 3.6 μm and the pore depth is ～21 nm. Additionally, the porosity throughout the surface of capsules in-between nanopetals is an advantageous characteristic feature to improve the drug/paclitaxel (PTX) loading capacity. It is a unique and novel approach to design NFCs, which are a potential payload for nanomedicine and cancer therapy. Furthermore, NFCs were used to evaluate the loading efficacy of drugs and showed ～78% (wt/wt%) of the PTX loading. Moreover, NFCs showed ～74% drug release at physiological body temperature. Thus, NFCs showed remarkable release at acidic pH medium. However, PTX released from NFCs showed greater cell inhibition (i.e., ～79%) with an increase of the PTX concentration after 24 h incubation over HeLa (human epithelial cervical cancer) cells. Besides, PTX released from NFC showed significant (～34%) cell killing capacity. Such promising NFCs are recommended for breast, liver, and lung cancer therapeutics.
Tumor intelligent targeting and environmental double responsiveness siRNA delivery system and its preparation method and application
-
Paragraph 0039; 0040; 0041; 0043, (2019/02/19)
The invention particularly discloses an intelligent targeting and environmental dual-responsibility siRNA [short interfering RNA (ribonucleic acid)] delivery system for tumor, a preparation method and application. The siRNA delivery system is characterized in that siRNA is concentrated and compounded in nanometer particle nucleuses by the aid of acid-sensitive amphiphilic three-block polymers, and intermolecular disulfide bonds are formed by PAsp(MEA) on sub-surfaces, so that the siRNA can be protected, and the intelligent targeting and environmental dual-responsibility siRNA delivery system can respond to release of the siRNA in reductive cytoplasm. The acid-sensitive amphiphilic three-block polymers comprise polyethylene glycol block-intermediate block-acid-sensitive block three-block copolymers, intermediate blocks comprise polyaspartate acyl mercaptoethylamine, and acid-sensitive blocks comprise poly (diisopropyl amine) ethyl methacrylate. The intelligent targeting and environmental dual-responsibility siRNA delivery system, the preparation method and the application have the advantages that the siRNA delivery system can be applied to preparing intelligent targeting siRNA nanometer medicines for the tumor and is low in N/P ratio dependence degree, and the siRNA can be quickly and completely released at targets; a novel idea can be provided for gene delivery systems, and the intelligent targeting and environmental dual-responsibility siRNA delivery system, the preparation method and the application have important significance on preparing clinical diagnosis and treatment medicines for the tumor.
Preparation method of drug-loaded nano-micelle capable of releasing anti-cancer drug in tumor matrix as well as product and application of drug-loaded nano-micelle
-
Paragraph 0058-0060, (2019/12/25)
The invention relates to a preparation method of a drug-loaded nano-micelle capable of releasing an anti-cancer drug in a tumor matrix as well as a product and an application of the drug-loaded nano-micelle, which belongs to the technical field of drug carriers. The preparation method comprises the following steps: the beta-benzyl aspartate is prepared, benzyloxycarbonyl aspartic anhydride is prepared, a polyaspartic acid benzyl ester polymer is prepared, a carboxylation-polyaspartic acid benzyl ester polymer is prepared, a carboxyl-polyaspartic acid dimethylethylenediamine polymer is prepared, a polyaspartic acid dimethylethylenediamine-polyaspartic acid benzyl ester polymer is prepared, a poly(aspartic acid-dimethylethylenediamine)-poly (aspartic acid-mercaptoethylamine) polymer is prepared, and drug-loaded nano-micelle for releasing an anti-cancer drug in a tumor matrix is prepared. The drug-loaded nano-micelle prepared by the preparation method has double sensitivities of pH sensitivity and reduction sensitivity, can accurately release drugs, and effectively improves the tumor treatment effect.
A pH and temperature double sensibility of nanometer vesicle and its preparation method and application
-
Paragraph 0044; 0048-0050, (2019/02/19)
The invention belongs to the fields of high polymer chemistry and biomedical engineering, and particularly discloses a pH and temperature sensitive polymer. The polymer is composed of a hydrophilic polyethylene glycol segment, and a lyophobic poly-(aspartic acid-diethyl-ethylenediamine-co-histamine-co-diisopropyl ethylenediamine) segment, and the ratio of the hydrophilic segment to the lyophobic segment is (1:10)-(1:12). The pH and temperature sensitive polymer can be used for preparing nano-vesicles loaded with hydrophilic anti-tumor drugs or/and ultrasonic contrast agents, and the nano-vesicles can be used for preparing tumor diagnosis drugs or tumor treatment drugs.
Photo-thermal chemotherapy and treatment combined microenvironment responsive drug-loading nano micelle preparation method and application
-
Paragraph 0046; 0052; 0055-0056, (2019/06/27)
The invention discloses a photo-thermal chemotherapy and treatment combined microenvironment responsive drug-loading nano micelle preparation method and application. A nano micelle comprises TIID-BT,a medicine active component and an amphiphilic block polymer, and the amphiphilic block polymer refers to polyethylene glycol-polyaspartic acid. By synthesis, a near infrared TIID-BT dye and a DOX chemotherapy drug are loaded on the specific nano micelle at the same time to obtain the nano micelle which is capable of giving play to photo-thermal treatment and chemotherapy at the same time. The nano micelle enables DOX to avoid a combination effect of opsonin and a capturing effect of an MPS system to form a stable and long-acting drug delivery system with high drug loading capacity, and accordingly an antitumor effect of DOX is improved while DOX resistance of tumors is changed. In addition, due to loading of the TIID-BT dye in the nano micelle, in-vivo application effects of the TIID-BT dye are improved, combination of hoto-thermal treatment and chemotherapy is realized, and in-vivo tumor treatment effects are improved due to synergistic effects of DOX and TIID-BT.
Thermoresponsive Alignment Media in NMR Spectroscopy: Helix Reversal of a Copolyaspartate at Ambient Temperatures
Schwab, Mira,Schmidts, Volker,Thiele, Christina M.
, p. 14373 - 14377 (2018/09/20)
Poly(aspartic acid esters) are known to form either right-or left-handed α-helices depending on the ester group in the side chain, on solvent and/or on temperature. Polyphenethyl-l-aspartates (PPLA) exhibit a helix reversal from the right- to the left-handed form with increasing temperature. We have recently reported the application of polyphenethylaspartates as helically chiral alignment media. The thermoresponsivity observed for these polymers offers the possibility to measure different orientations of analytes before and after helix reversal of the alignment medium at 373 K. Herein we present a synthesized copolymer of phenethyl- and benzylaspartate as a new alignment medium undergoing this helix reversal at 303–313 K. Thus, the measurement of residual dipolar couplings (RDC) before and after the helix reversal is allowed for at ambient temperatures. A complete sign change of all 1H–13C RDCs was observed, which is close to the highest possible difference in NMR spectra.
Polymeric micelles for pH-responsive lutein delivery
Zhang, Dongxue,Wang, Lina,Zhang, Xin,Bao, Decai,Zhao, Yanjun
, p. 281 - 286 (2018/03/26)
There has been growing interests in nanoparticulate delivery of the natural carotenoid, lutein for anti-cancer therapy. However, the low aqueous solubility of lutein and the poor lutein release from nanocarriers limit its bioavailability and therapeutic o
UNIMOLECULAR NANOPARTICLES FOR EFFICIENT DELIVERY OF THERAPEUTIC CATIONIC PEPTIDES
-
Paragraph 0125, (2018/09/12)
Provided herein are peptides comprising an amino acid sequence having at least about 85% sequence identity to RYRPRAPIIAVT (SEQ ID NO: 1). These cationic peptides inhibit PKM2 methylation and may be used in the treatment of breast cancer and other diseases or conditions in which PKM2 is overexpressed. Such PKM2 peptides may be delivered to cancer cells using pH sensitive unimolecular nanoparticles comprising anionic polymers.
