Comb-like poly(l-cysteine) derivatives with different side groups: synthesis via photochemistry and click chemistry, multi-responsive nanostructures, triggered drug release and cytotoxicity

Abstract

A series of comb-like graft polypeptides having different side groups and tunable grafting ratios were prepared by sequential photocleavage reaction and Michael-type thiol-ene addition, as fully characterized by 1 H NMR, gel permeation chromatography, FT-IR, and circular dichroism spectroscopy. The grafting ratio of the resulting polypeptides was close to the photolysis ratio of o-nitrobenzyl derived poly(L-cysteine) precursors. Both electrolytic acrylic acid (AA) and 2-(dimethylamino) ethyl acrylate (DMAEA) produced a larger disturbance on the ordered conformations than neutral poly(ethylene glycol) (PEG) methyl ether acrylate although the molecular weight and size of AA and DMAEA are much smaller than those of PEG. The polypeptide vesicles and micelles with neutral or electrolytic corona could be facilely fabricated from these side group modified poly(L-cysteine)s, and the polypeptide vesicles exhibited both light-and redox-sensitivity in aqueous solution. As characterized by MTT assay, flow cytometry, and CLSM, the anticancer drug doxorubicin (DOX) loaded nanoparticles quickly entered into HeLa cells and presented photo-and reduction-triggered cytotoxicity. The half maximal inhibitory concentration of HeLa cells (IC 50 ) for the irradiated nanoparticles dropped to 0.40 µg DOX equiv/mL compared to 1.27 µg DOX equiv/mL for non-irradiated sample; however, the IC 50 for the irradiated sample increased about 1.5-fold after the BSO inhibitor treatment. Importantly, this work not only establishes a facile method for the preparation of comb-like graft polypeptides by the combination of photochemistry and thiol-ene click chemistry, but also provides a promising platform for on-demand nanomedicine and cancer therapy.

Plasmonic, Targeted, and Dual Drugs-Loaded Polypeptide Composite Nanoparticles for Synergistic Cocktail Chemotherapy with Photothermal Therapy

“…S1-2). 38,39 We then fabricated the glyco-PEGylated polypeptide micelles with a disulfide-bond-cross-linked core (i.e., LAC ○ M ) by aqueous self-assembly process of amphiphilic PC 40 -g-PEG 5 -LAC 5 followed by H 2 O 2 oxidation (Fig. 1).…”

“…We synthesized lactose (LAC) and PEG grafted polycysteine terpolymer (PC-g-PEG-LAC) by sequential UV photolysis and thiol-ene click chemistry and then fabricated the glyco-PEGylated polypeptide micelles according to our previous publications. 38,39 The blank polypeptide micelles and/or their DOX-loaded counterparts were used as templates to generate the gold-embedded composite nanoparticles by forming multivalent Au-S bonds. Finally the DOX-loaded 8 Mercury-400 spectrometer at room temperature and tetramethylsilane was used as an internal standard.…”

Preparation of hybrid triple‐stimuli responsive nanogels based on poly(L‐histidine)

“…Amphiphilic hybrid (PEO)‐ b ‐polypeptides that self‐assemble into micelles are becoming promising candidates for stimuli‐responsive drug delivery nanosystems . It is known that the instability of polymeric micelles leads to short circulation times and uncontrolled drug release behavior.…”

Synthesis and Application of Aurophilic Poly(Cysteine) and Poly(Cysteine)-Containing Copolymers

“…Using PEG acrylate yields a comb-like copolymer with a p( l -Cys) backbone, grafted with PEG and the degree of grafting is controlled by the degree of photodegradation of the o -nitrobenzyl groups. These comb-like copolymers self-assemble into vesicles or micelles depending on grafting ratio; with copolymers with lower grafting ratios (less than 30%) forming vesicles; at very high grafting ratios (above 75%) no self-assembly was achieved [ 55 , 56 ]. This is an interesting observation as the self-assembly of PEGylated polyaminoacids/polypeptides into micelles and nanoparticles or aggregates is often described, however, vesicles are rarely observed [ 57 ].…”