Preparation Of Poly(Amino Acid) Nanomicelles And Its Application In Antitumor Drug Delivery

Malignant tumor(commonly known as cancer) is a serious threat to human health and ranks as one of the most common cause of death. However, the drawbacks of smallmolecule drugs used clinically are poor drug targeting function, short metabolic time and drug-resistant properties, which lead to lower efficiency and serious toxic sideeffect. To overcame these drawbacks, we can chemically or physically incorporate the anti-tumor drug onto the nano-carriers.(1) In order to solve problem of small-molecule drug delivery, the biocompatible sensitive intelligent good poly amino acid nano-micelle(micelle of PLG nb-PEG2,3LGm) for drugs encapsulation in delivery of anti-tumor drug are designed according to the micro-environment differences existed in both internal and external tumor cell. The micelle in vitro release test under circular dichroism(CD) with different temperature and p H value showed the characteristics of dual sensitive to temperature and p H value. In cell test, it showed good cell compatibility, which proved that PLGnb-PEG2,3LGm is a good encapsulation nano-micelle material of anti-tumor drug.(2) The point of the first part is to solve the problem of drug encapsulation, but there are five problems faced in the process of nano-drug delivery.i. Stability and half-life of nano-particles existed in the circulatory system.ii. In nano-particles metastasis from the circulatory system to the lesions, the main problems are concentration and target.iii. Nano-particles permeate deeply into the tumor tissue from lesion, the main problem is penetration.iv. In the process of nano-particles internalizing into cancer cells from the environment within the lesion site, the main problem are endocytosis and cleaning mechanism.v. Whether nano-particles into cancer cells can be released effectively, and evade the clearing mechanisms within the cell, then play effect.In this paper we focuson the conception to solve the fourth problem: endocytosis. The proposal of designing a variety of surface modifications(positive ion, negatively ion, dipolar ion, oligomeric PEG) to test the endocytosis function is pointed in this paper. With multiple modifier azide, make a side group with end alkynyl polyamino acid block, and then graft the various modifiers with method of "click", then get different micelles pre-assembled materials. By micellar assembled in the same conditions, these materials are emerging nano-micelles with different surface modification, then particle size, different potential and subsequently the characterization of different cell endocytosis.