Synthesis and characterization of polymer PEG-b-PAEBEA文献综述

Background:

For a long time, polymeric micelles have raised attention of scientists because it shows good characters like protection of drug from metabolism in physiological fluid and controlled release of drug at target sites¹. Also, it represents an important delivery for hydrophobic chemo-drugs because the hydrophilic shell of amphiphilic polymer with hydrophobic core makes it easier to stabilize. However, there are still many challenges in improving drug loading efficiency, colloidal uniformity, strong stability and drug release.

A recent research has shown a method to do modification on polymer to enhance its potency. Inspired by this, we synthesize our polymer with structure like that and would like to characterize its functioning.

Characterizing the polymer is of great significance in a project because this plays a decisive part in our choice of drug. The interactions between polymer and drugs should be made clear and strong. According to the structure, there are three effects in loading drug and miRNA and dissociation of them.

1. Quaternary amine is positively charged so it can bond with miRNA which is negatively charged.
2. Hydrophobic drug is able to be encapsulated via donor-acceptor interactions between phenyl-boronic acid group and electron-donor drug.
3. Boronic acid is sensitive to ROS which accumulates in cancer cell microenvironment. Once it is oxidized, drug will be released, followed by the transition of positively charged quaternary amine to become neutral tertiary amine, releasing the miRNA at the same time for potential synergistic effect.

Literature review

Preface:

Nanoparticles brings many advantages. It enables the delivery of poorly water-soluble compound, targeted transporting to expected sites, transcytosis of drug across hydrophobic membrane barrier and so on. Previously, hydrophobic interaction between polymer and drug is the primary driving force while it is non-specific and weak. That results in extremely low drug loading efficiency and other problems including colloidal ununiformity. Fortunately, a facile approach has been introduced to specifically enhance polymer-drug interaction. Donor-acceptor interaction is common between electron donors and receptors and it is stronger than hydrophobic interaction so it is expected to yield micelles with high drug loading efficiency. Boronic acid, the acceptor and amine, the donor are subjects we focused on.

Body:

Donor-acceptor interaction is also called as coordination bonding, referring to electron donors and acceptors. Boronic acid is typical of electron acceptors since the boron atom has outmost electron number of 3. At the same time, the most possible donor atoms in hydrophobic drug can be nitrogen whose outmost electron number is 5. Boron and nitrogen atoms can form donor-acceptor interaction to stabilize. Whatrsquo;s more, the coordination is reversible and will not change the molecular structure of drugs so drugs can be released and potentiate their efficacy.

On the other hand, boronic acid is quite sensitive to reactive oxygen species which accumulate in cancer cells microenvironment. With targeted species like that, micelles are able to reach tumor and target at cancer cells. This makes great difference to strengthen the anticancer potency instead of killing normal cells.