Gold nanoparticles loaded chitosan encapsulate 6-mercaptopurine as a novel nanocomposite for chemo-photothermal therapy on breast cancer

Abstract

Background As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect. Methods CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay. Results Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively. Conclusion The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP. Graphical Abstract

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications

“…[157] Due to these advantages resulting in increased effectiveness and reduced side effects, encapsulation is increasingly used to deliver a variety anticancer, antibacterial, anti-inflammatory, and antipsychotic agents. [158]…”

“…Additionally, in a murine xenograft tumor model, PTX-NPs exhibited excellent biosafety and outstanding anti-tumor activity. [172] Faid et al [158] encapsulated 6-mercaptopurine (6MP) into CNPs (6MP-CNPs) and loaded them onto gold NPs to create a 6MP-CNPs-AuNPs nanocomposite. While 6MP production reached a peak of approximately 39 % at 100 μM, the antiproliferation activity of 6MP-CNPs-AuNPs and 6MP-CNPs was significantly enhanced, reaching IC 50 values of 8.7 and 9.3 μM, respectively.…”

“…A well‐designed delivery system can be tailored to specifically reach their target and improve their penetration, while the combination of two or more drugs can result in additive or synergistic effects, thereby increasing the effectiveness compared to monotherapy [157] . Due to these advantages resulting in increased effectiveness and reduced side effects, encapsulation is increasingly used to deliver a variety anticancer, antibacterial, anti‐inflammatory, and antipsychotic agents [158] …”

18F-fluorodeoxyglucose (18F-FDG) Functionalized Gold Nanoparticles (GNPs) for Plasmonic Photothermal Ablation of Cancer: A Review

“…In particular, the effect on cellular proliferation of the human breast carcinoma cell line MCF7 was demonstrated, comparing free 6MP, which produces maximum inhibition of 39% at 100 μM, 6MP-CNPs with an IC50 at 9.3 μM, and 6MP-CNPs reaching 8.7 μM. The encapsulation of 6MP guarantees higher anti-proliferation activity, an augmented intracellular uptake, and thus a reduction of side effects [ 102 ]. Hyaluronic acid (HA)-Au@SiO2@Au NPs were proposed for the treatment of bladder and prostate cancers in mice.…”

Niosomes containing paclitaxel and gold nanoparticles with different coating agents for efficient chemo/photothermal therapy of breast cancer

“…Recently, AuNPs with various surface coatings (polymers) and modifications have been studied as novel PTT agents [19]. Also, the coating of AuNPs with organic or biological molecules has attracted enormous interest in reducing the toxicity of bare AuNPs and preventing the NPs aggregation which influences the optical properties and alters their activation under laser radiation [23].…”