Polymer-based nanosystems have been extensively explored either as therapeutic agents or bioimaging probes in the cancer diagnosis. However, very few systems are successful in combining both therapy and imaging. Herein, a new class of norbornene based copolymer, Nor-Dox-Cob-Btn is proposed as potential theranostics agent for tumor diagonosis. The copolymer (Nor-Dox-Cob-Btn) with doxorubicin, cobalt carbonyl complex, and biotin as pendent functionalized group is synthesized, using ring opening metathesis polymerization (ROMP). The cell viability, drug release, NMR relaxation, NMR 1-D image and Epi fluorescence microscopy studies on Nor-Dox-Cob-Btn nanocarrier are thoroughly studied. The effect of nanocarrier on transverse relaxation (T 2 ) of water molecule and NMR 1-D image suggest that the nanocarrier has the potential application in magnetic resonance imaging agent. The T 2 -weighted MRI agent, along with biotin receptor assisted pH responsive doxorubicin release from Nor-Dox-Cob-Btn, prompts us to envision this newly developed polymer for future application in theranostics.
■ INTRODUCTIONDoxorubicin is a well-known frontline anticancer drug, however due to cardiotoxic effect of doxorubicin, it is always necessary to protect this drug from other healthy cells and tissues inside body. 1 There are several different models available to guide this drug more precisely into the tumor cells, for example, polymer, nanoparticle, liposome. 3 However, polymer based delivery vehicle emerged as a superior over all other existing systems due to its pharmacokinetics and biodistribution profiles via the enhanced permeability as well as retention (EPR) effect. 4 These systems also help to maintain the therapeutic concentration over long periods of time. 2−4 There are mainly two approaches to deliver drugs site-specifically to the tumor cells, namely, covalent and non covalent approaches. 5,8 Drugs encapsulated inside the polymeric aggregates can be placed inside the body for using it localized delivery following the burst mechanism. 3,5,6,8 On contrast, in stimuli responsive covalently attached drug (e.g., pH sensitive, light sensitive, etc.) to the polymeric system gives the sustained release of drug to the tumor cells over long period. 11 There are several reports available in literature based on the pH sensitivity linker, for example hydrazone, ester, and amide, in which hydrazone linker is the most commonly used for the sustained release. 11 The medical application of polymeric nanocarrier has enormous potential to improve the therapeutic efficacy, particularly in cancer therapy. The attachment of folate or biotin functionality to the same polymeric prodrug makes the system more site-specific via receptor mediated drug delivery. 5,7,9 This also improves the survival rates of healthy tissues and cells. The attachment of magnetic particles helps the drug-carrier system further, as this magnetic particle can be utilized as MR imaging agent. 11 Magnetic as well as drug containing polymersomes have a great potential for both ...
