• 专利标题:   Building nanoparticle-based drug carriers, used in controlled, intracellular administration of drugs involves manipulating nanoparticle protein corona by e.g. high throughput data mining and incorporating drug into conjugate.
  • 专利号:   WO2021146851-A1, CN114787628-A, US2023039443-A1
  • 发明人:   KOHLI S, YAZDI A Z, CHEN P
  • 专利权人:   NANOPEPTIDE QINGDAO BIOTECHNOLOGY LTD, NANOPEPTIDE QINGDAO BIOMEDICINE CO LTD, NANOPEPTIDE QINGDAO BIOTECHNOLOGY LTD
  • 国际专利分类:   A61P035/00, G01N033/543, G01N033/547, A61K047/54, A61K047/68, A61K047/69, C12N015/113, G01N033/68
  • 专利详细信息:   WO2021146851-A1 29 Jul 2021 G01N-033/543 202168 Pages: 19 English
  • 申请详细信息:   WO2021146851-A1 WOCN073273 20 Jan 2020
  • 优先权号:   CN80080095, WOCN073273, CN80080095, US17759046

▎ 摘  要

NOVELTY - Building (M1) nanoparticle-based drug carriers comprises manipulating the nanoparticle protein corona through a combination of (A) liquid chromatography tandem mass spectrometry on the nano-scale of corona extracts prepared from nanoparticle formulations, (B) high throughput data mining for determining tens of thousands of protein-protein interactions associated with the corona extracts to then determine which of the corona proteins are ideal to recruit endogenously for increasing likelihood of cell specific uptake, (C) antibody conjugation, where antibodies against the ideal corona protein are determined by the algorithm and (D) incorporating the drug into the nanoparticle-antibody conjugate. USE - The methods are useful for building nanoparticle-based drug carriers for the controlled, intracellular administration of drugs to cancer cells (claimed), where the cancer is lung cancer, breast cancer, or colorectal cancer. No biological data given. ADVANTAGE - The method: builds nanoparticle based drug carriers which is able to manipulate the corresponding protein corona for specific and potent drug delivery to cancer cells, increases the abundance of protein in the corona for cancer-cell specific uptake, utilizes a series of polymers with ethyl and oxide functionalities to enhance solubility; and is economical. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are also included for: (1) building (M2) nanoparticle-based drag carriers for the controlled, intracellular administration of drugs by manipulating the nanoparticle protein corona through a combination of (AA) exposing nanoparticle formulations to human serum with normalized surface area (of the nanoparticles) to volume (culture volume) ratios over a set incubation time followed by corona isolation for nano LC-MS/MS analysis, (BB) deploying a series of scripts over a series of pre-existing proteomics data repositories for distinguishing ideal corona proteins for endogenous recruitment, (CC) employing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-N-hydroxy succinimide crosslinking for conjugating antibodies against the ideal corona protein to the ideal nanoparticle formulation and (DD) employing passive adsorption to conjugate siRNA to the nanoparticle surface; and (2) a nanoparticle based drug delivery system able to manipulate the corresponding protein corona for specific and potent drug delivery to cancer cells comprising a series of monoclonal antibodies tethered to the nanoparticle surface to increase the abundance of protein in the corona for cancer-cell specific uptake and a series of polymers with ethyl and oxide functionalities to enhance solubility.