Engineering Camptothecin-Derived Norbornene Polymers for Theranostic Application

Abstract

A multifunctional stimuli-responsive nanotheranostic agent provides huge benefits in nanomedicine by combining both the diagnostic agent and the drug molecule in a single system. This nanosystem is capable of doing multiple tasks, for example, diagnosis, drug delivery, and monitoring the therapeutic response. Hence, theranostic agents are expected to play a significant role in personalized medicine. Herein, a new class of nanotheranostic agents, Pnr-Cbt-Cpt-Pg-Bn, is proposed for the effective delivery of camptothecin. This new class of polymer has been functionalized with a superparamagnetic norbornene cobalt unit for its use in magnetic resonance imaging (MRI). The NMR one-dimensional image confirms the MRI capability of this nanotheranostic agent. This is further modified with the poly(ethylene glycol)–biotin moiety for biocompatibility and site-specificity. The uniqueness of the design is confirmed by an in vitro study where a greater uptake of the nanotheranostic agent is observed when compared with free drugs. Hence, this new class of copolymer shows improved potential as nanotheranostic agents in drug delivery.

Polymer based Nano-Assemblies: Very Efficient Carrier in the Field of Cancer Chemotherapy

“…doxorubicin, camptothecin, cis-platin) suffer either from solubility or sitespecificity causes for severe side-effects in real applications [3]. To deal with these different drawbacks of small molecule drugs, researchers have employed different delivery vehicle carrying the chemotherapeutic agent either with non-covalent encapsulation or attached with different stimuli responsive (pH, thermal, and enzymatic) linkers to the delivery vehicle [3][4][5][6][7][8][9][10][11][12][13]. This vehicle carries single or multi drug component in aqueous environment form self-assembled nano-structure by protecting the drugs into its hydrophobic core and deliver the drug once it reaches to the affected area [3][4][5][6][7][8][9][10][11][12][13].…”

“…These all particularly form excellent nano-assemblies in aqueous environment due its amphiphilicity present in it [14][15][16][17][18]. Polymer based drug delivery system is one of those which form excellent nano-assemblies when it functionalized with hydrophilic PEG group [7,9,[11][12][13]. The drug can deliver through this nano-carrier either by non-covalent encapsulation or covalently attached with different stimuli responsive linkers [5,7,[13][14][15].…”

“…Polymer based drug delivery system is one of those which form excellent nano-assemblies when it functionalized with hydrophilic PEG group [7,9,[11][12][13]. The drug can deliver through this nano-carrier either by non-covalent encapsulation or covalently attached with different stimuli responsive linkers [5,7,[13][14][15]. The polymer based nano-vehicle shows enhanced cytotoxic effect due to its plasma stability which eventually helps to increase the permeation and retention effect (EPR) [5][6][7][8][9][10][11][12][13][14][15].…”

“…The drug can deliver through this nano-carrier either by non-covalent encapsulation or covalently attached with different stimuli responsive linkers [5,7,[13][14][15]. The polymer based nano-vehicle shows enhanced cytotoxic effect due to its plasma stability which eventually helps to increase the permeation and retention effect (EPR) [5][6][7][8][9][10][11][12][13][14][15]. Due to leaky vesicular nature of the blood vessel around the tumour help these nano-vehicles to reach the targeted sites [8].…”

“…Hence, functionalization of these site-specific motifs into the nano-assemblies, which targets the receptors those are over expressed on the surface of the cancer cell, make the system more site-specific. Further, these nano-assemblies are internalized efficiently by following receptor mediated endocytosis, a well-known mechanism followed by mammalian cells (Figure 2) [7,9,13].…”