ph and oxidation-reduction dual-sensitive layer cross-linking nanoparticle as well as preparation method and application thereof
A nanoparticle, sensitive technology, applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of fast clearance rate, poor targeting, poor controlled release effect, etc., to achieve improved enrichment and retention, low toxicity, and biocompatibility good sex effect
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[0047] figure 1 It is a schematic diagram of the double sensitive layer cross-linked nanoparticles of the embodiment of the present invention. From figure 1 It can be seen that the double sensitive layer cross-linked nanoparticles of the present invention have a three-layer structure, the outer layer is RGD with tumor targeting function and zwitterionic polymer PCB, and the interlayer is a shell layer cross-linked by disulfide bonds, which is hydrophobic. The drug is loaded in the inner core through hydrophobic interaction with the hydrophobic segment PDPA. Example 1 (I-1)
[0048] The preparation method of triblock RGD-PCB-b-PDS-b-PDPA polymer includes the following steps:
[0049] (a) Preparation of PCB(tBU)-b-PDS-b-PDPA polymer
[0050] Add the reversible addition-fragmentation chain transfer polymerization (RAFT) chain transfer agent trithiododecyl-2-isopropanoate (CTAm) (36.5mg, 0.1mM) and zwitterionic monomers in the shlenk reaction tube in sequence Betaine tert-butyl carbox...
Example
[0059] Example 2 ~ Example 12
[0060] The equipment and operation are the same as in Example 1, except that the carboxybetaine tert-butyl methyl methacrylate (CB-tBU), methacrylamide ethylpyridine disulfide (DS) and diisopropylamino methacrylate are adjusted. The ratio of ethyl ester (DPA) and other monomers to the chain transfer agent trithiododecyl-2-isopropanoate (CTAm) to obtain triblock polymers with different degrees of polymerization, as shown in Table 1:
[0061] Table 1: pH and redox dual sensitive polymers
[0062]
[0063] N a It is the molar ratio of RGD to PCB-b-PDS-b-PDPA triblock polymer.
Example Embodiment
[0064] Example 13 (I-13):
[0065] According to the method and device of Example 1(a), CB-tBU was replaced with RGD-linked polyethylene glycol acrylate (RGD-PEG480-AC), and the number average molecular weight of the polyethylene glycol segment was 480 to obtain RGD-PEG480- b-PDS-b-PDPA. NMR characterization of its composition RGD-PEG480 10 -b-PDS 10 -b-PDPA 25 (I-13), the subscript is the degree of polymerization of the corresponding monomer.
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