Graphene quantum dot-based theranostic agents for active targeting of breast cancer

Abstract

A novel graphene quantum dot (GQD)-based nanocarrier labeled with Herceptin (HER) and b-cyclodextrin (b-CD) was developed as a promising theranostic candidate for the treatment of breast cancer. Each component of this nanocarrier plays a critical role in providing multiple functions to achieve enhanced anticancer activities. HER provides active targeting to HER2-overexpressed breast cancer to enhance accumulation in the cancer cells. b-CD provides a site for loading of a hydrophobic anticancer drug, doxorubicin (DOX), via "host-guest" chemistry. The nanocarriers also provide diagnostic effects due to the blue-color emission of the GQDs. In response to the acidic environment of cancer cells, the GQD-complex degraded rapidly and the DOX was released in a controlled manner to inhibit proliferation of cancer cells.This multi-functional drug delivery system leads to a synergistically enhanced anticancer strategy which provides treatment and diagnosis. The intracellular trafficking results, along with cell viability and confocal laser scanning microscopy, suggest that the GQD-complex offers a viable strategy for HER2-overexpressed breast cancer-targeting drug delivery applications.

Dual pH- and GSH-Responsive Degradable PEGylated Graphene Quantum Dot-Based Nanoparticles for Enhanced HER2-Positive Breast Cancer Therapy

“…Amine-functionalized CNPs were synthesized by the pyrolysis of L-glutamic acid (the detailed procedure is described in our previous report [25]). 3,3 -Dithiodipropionic acid (SS-COOH, 99%), polyethylene glycol (PEG, MW = 3000 g/mol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC, >97%), 4-dimethylaminopyridine (DMAP, >98%), N-hydroxysuccinimide (NHS, 98%), and doxorubicin hydrochloride (DOX, -NH 3 + Cl − salt form, >98%) were obtained from Aldrich (St. Louis, MO, USA), and βCD (>98%) obtained from TCI (Tokyo, Japan) were purchased and used as received.…”

A Practical Guide to Prepare and Synthetically Modify Graphene Quantum Dots

“…A clever way to combine two organic molecules bearing alcohol and amine functionality is to form a carbamate which can be facilitated using 1,1′‐carbonyldiimidazole (CDI) . Carbamate chemistry was used to join GQDs (synthesized from pyrolyzing ʟ‐glutamic acid, thereby generating GQDs which exhibit amino functionality) with β‐cyclodextrin ( 32 , Scheme ) to form GQD‐βCD 34 . The reaction was carried out in PBS buffer and a 1:1 ratio of β‐cyclodextrin to CDI was used.…”

“…The reaction was carried out in PBS buffer and a 1:1 ratio of β‐cyclodextrin to CDI was used. After gentle heating for four days and a dialysis purification step, 232.5 mg of the desired material was isolated; a reasonable mass recovery given 500 mg of GQD‐NH 2 was used in the reaction . To the best of our knowledge, this is the only example of carbamate chemistry having been performed on GQDs, however the high‐mass recovery reported would suggest that this method is an excellent candidate for post‐modification of GQDs when the appropriate functional groups are present.…”

The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

“…There are a lot of strategies that can be explored to achieve the aforementioned objectives. Stimuli-response nanomedicines use the tumor microenvironmental features to trigger a specific response such as releasing the nanosystems cargo (e.g., siRNA, chemotherapy agents) when there is a variation in pH [44] or redox state of the cell [45], or in the presence of overexpressed enzymes [36]. These stimuli change the structure of the nanoparticle facilitating the release of the cargo.…”