Redox sensitive hyaluronan acid-SS-poly(ε-caprolactone) four-arm star-shaped polymers for tumor treatment文献综述

Redox sensitive hyaluronan acid-SS-poly(ε-caprolactone) four-arm star-shaped polymers for tumor treatment

1. Background

Cancer is highly aggressive and is one of the leading causes of mortality in patients in the worldwide. Chemotherapy, although is a commonly used cancer therapy strategy, has many inevitable problems such as severe side effects, limited efficacies, and the possibility to trigger multidrug resistance.

Thus, the development of smart nano-drug delivery systems (NDDSs) with excellent tumor-targeting ability and accurately controlled release profile has attracted a great deal of attentions in recent years. Up to now, a large variety of multifunctional nanoplatforms responsive to various external and/or internal stimuli (e.g. light, heat, ultrasound, magnetic field, acidic pH value and redox environment) have been rationally designed and demonstrated to be efficient for cancer therapy with higher efficacy and limited side effects compared to conventional chemotherapy in many pre-clinical animal studies ^[1].

Recently a new technique has been searched which is able to deliver therapeutic factors very efficiently to the targeted sites because of its great importance to achieve an excellent therapeutic effectiveness in cancer treatment^[2]. The star shape polymers has been talked about because of its unique properties, (unique rheological and dynamic properties) compared to linear analogues of identical molecular weight and monomer composition, and we do not forget the Drug Encapsulation Properties and Self-Assembly Behavior in Solution.

Also, star-shaped polymers show lower melt temperatures, lower crystallization temperatures and lower degrees of crystallinity than comparable linear analogues^[3], and the important thing is that it has been widely investigated as Nano carriers for drug delivery. Thus here star shape polymer will be used to reach a solution to eliminate the cancer permanently.

Star-shaped polymers are a class of branched macromolecules, consisting of a core ,and a numeral of arms radiating from the core. The core could be molecule, or macromolecule or atoum。 The arm could be considered as homogeneous if the arms are equivalent in both structure and chain length, and heterogeneous if the arm variable in lengths and structures^[4].

For synthesis of Star-shaped polymers, can synthesized by three methods which are: the “arm-first”, “core-first”, and the grafting-onto approaches, and With the development of polymer engineering, Complex star-shaped polymer structures can be easily made , which can cause a lot of exceptional properties and applications^[5].

recently, Poly (ε-caprolactone), (PCL) which is also known as polycaprolactone attracted significant attention, it is aliphatic polyesters which has been known for its distinctive properties of biocompatibility, biodegradability and high hydrolysability in the human body, Furthermore , PCL is suitable for long-term delivery that spans more than one year , due to this properties it was used in preparing several delivery systems in the form of microspheres and nanospheres. Several drug categories were also encapsulated in PCL to deliver the targeted drug and to release the controlled drug. Other properties such as low melting temperatures in the physiological range and slow crystallization kinetics^[6,7].

And about hyaluronan acid (HA) is a natural hydrophilic polysaccharide that Which is characterized by distinctive characteristics such as biodegradability, biocompatibility and non-immunogenicity, in addition to that it is a major ligand for the adhesion receptor of CD44, which is over-expressed on the surface of many tumor cells.

Consequently, stimuli-sensitive nanocarriers based on HA derivatives have a big possibility as theranostic stage for drug delivery and MRI^[8].