Polymer based nanotheranostic agents have attracted a lot of interest in recent years because of their capability to simultaneously diagnose and treat the disease. Such constructs also enable monitoring of the treatment in real time. Polymer based theranostic agents comprise of three main components: a biocompatible polymeric construct that acts as a vehicle, a therapeutic agent to treat the disease, and an imaging agent to monitor the localized delivery of the drug. Nanogels, with their excellent stability and biocompatibility, serve as ideal nanocarriers. Moreover, their small size allows preferential accumulation at the tumour site through enhanced permeability and retention effect. This presentation will outline different approaches for fabricating poly(ethylene glycol) based multi-functionalizable nanogels containing maleimide and amine-reactive moieties. Since the maleimide functional group is reactive toward thiols and dienes through the Michael and Diels-Alder reactions, respectively; copolymers were crosslinked in aqueous media using dithiol, diamines or bis-furan based linkers to yield reactive nanogels. Nanogels were conjugated with drug and targeting units to achieve selective delivery to breast cancer cells. Doxorubicin, a widely used chemotherapeutic agent, was attached to the nanogels through the labile carbamate linker, allowing its release at acidic pH. Indeed, Doxorubicin, with its inherent fluorescence can be also used as a theranostic agents. To enhance the selectivity of the nanocarrier and provide targeted delivery, a cyclic peptide with high affinity toward integrin receptors overexpressed on various cancer cells was linked to the nanogel. Cellular internalization experiments showed increased uptake of targeted constructs compared to the non-targeted nanocarriers. It can be envisioned that facile fabrication and modular functionalization of these nanogels would promote their utilization as promising theranostic platforms to treat various diseases.

Fabrication of clickable nanogels from reactive copolymers: Novel nanocarriers for targeted therapy

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.