Gemcitabine Integrated Nano-Prodrug Carrier System

Abstract

Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner.

RETRACTED: Electroactive peptide-based supramolecular polymers

“…Thin films of peptide-OPV conjugates were used to promote 3T3 fibroblasts adhesion; however, an analogous pyrene-based conjugate was cytotoxic ​[ 27 ]. Fmoc-diphenylalanine peptides have also found applications in drug delivery ​[ 136 ], biological sensing [ 137 ], and cell culture [ [138] , [139] , [140] , [141] ] owing to their ability to assemble into nanofibers and form hydrogels under physiological conditions; however, Fmoc and pyrene are reportedly carcinogenic, and therefore, other alternatives such as naphthalene moiety, which is a common fragment of many clinically approved drugs, should be considered ​[ 100 ]. Peptide–naphthalene conjugates have high gelation efficiencies (as low as 0.07 ​wt %), demonstrate reasonable cytological compatibility ​[ 100 , 142 ], and even can be rendered proteolytically stable with the inclusion of d-amino acids ​[ 143 ].…”

A carbon nanotube-gemcitabine-lentinan three-component composite for chemo-photothermal synergistic therapy of cancer

“…31 However, its clinical application is limited because of short plasma half-life and poor uptake by cells. 32,33 In blood, the gemcitabine is rapidly deaminated into the inactive metabolite of 2′,2′-difluorodeoxyuridine, which is then quickly excreted through urine. 34 To address this problem, over the past decade, nanoscience-and nanotechnology-based carriers have been widely explored in the field of drug delivery.…”

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

“…[ 29 ] The nanoprodrug carrier system can also be constructed by blending one drug‐adjuvant with other adjuvants, for example, prodrug conjugate of anticancer drug gemcitabine (GEM) with protected glycine was noncovalently sandwiched by a pair of oppositely charged amyloid‐inspired peptides into nanofiber. [ 30 ] One important factor attributing to multidrug resistance is overexpression of P‐glycoprotein (P‐gp) which lead to reduced intracellular drug accumulation. Effective block the P‐gp efflux to accumulate the therapeutics in cancer cells is a promising approach.…”