Encapsulation of Platinum Anticancer Drug into Protein Nanocages as a Novel Nanomedicine for Targeted Delivery in Human Colon Cancer
Date Issued
2015
Date
2015
Author(s)
Lin, Shih-En
Abstract
Currently clinical treatment for colorectal cancer, in addition to surgical, adjuvant chemotherapy can significantly reduce the chances of recurrence of colorectal cancer patients. Platinum drugs mechanism of action is to block DNA synthesis, the first generation of cisplatin although have good treatment, but because of its side effects induce patient discomfort, so researchers have developed current clinical use of third generation platinum drugs oxaliplatin (Oxa). Although oxaliplatin side effects compared to cisplatin is not so high, but the side effects of nephrotoxicity and neurotoxicity affect the patient''s quality of life, so we began to combine different pharmaceutical carriers, hope with nanocarrier can enhance the efficacy and reduce side effects. Dichloro(1,2-diamino-cyclohexane)platinum(II) (DACH - Pt) is oxaliplatin active form, so in this study, we use the DACH - Pt as carried drugs. Protein carrier is a novel drug carrier, in my study I choose apoferritin (Apo), is a spherical iron storage protein composed of 24 subunits. Apo protein self-assembles naturally into a hollow nanocage with an outer diameter of 12 nm and an interior cavity 8 nm in diameter, this may lead to a longer circulation half-life and a better tumor accumulation rate, and it is a protein present in animal body, so the carrier has a high biocompatibility and biodegradable. Recently, it was reported that apoferritin binds to human cells via interacting with the transferrin receptor 1 (TfR1, CD71), and under normal circumstances the cells in order to maintain the balance of intracellular iron concentration so regard to a certain degree of expression TFR1. It is well known that TfR1 is highly expressed on human colorectal cancer cells and has long been used as a targeting marker for tumor diagnosis and therapy. The Apo nanocages can be collapse in an acidic environment (pH = 2) into subunits, and the process is reversible. When the pH is turned back to neutral, the Apo subunits will be reconstituted into a hallow structure, and almost in an intact appearance, so we can use this characteristic to achieve effectively loading into the cavity, such as pH dependent disassembly and reassembly can be exercise of construct Apo.
Subjects
Apoferritin
Human colocn cancer
SDGs
Type
thesis
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