RESUMO
Graphene quantum dots (GQDs) are nano-sized graphene slices. With their small size, lamellar and aromatic-ring structure, GQDs tend to enter into the cell nucleus and interfere with DNA activity. Thus, GQD alone is expected to be an anticancer reagent. Herein, we developed GQDs that suppress the growth of tumor by selectively damaging the DNA of cancer cells. The amine-functionalized GQDs were modified with nucleus targeting TAT peptides (TAT-NGs) and further grafted with cancer-cell-targeting folic acid (FA) modified PEG via disulfide linkage (FAPEG-TNGs). The resulting FAPEG-TNGs exhibited good biocompatibility, nucleus uptake, and cancer cell targeting. They adsorb on DNA via the π-π and electrostatic interactions, which induce the DNA damage, the upregulation of the cell apoptosis related proteins, and the suppression of cancer cell growth, ultimately. This work presents a rational design of GQDs that induce the DNA damage to realize high therapeutic performance, leading to a distinct chemotherapy strategy for targeted tumor therapy.
Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis , Núcleo Celular/efeitos dos fármacos , Dano ao DNA , Grafite/farmacologia , Pontos Quânticos , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Morte Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Composição de Medicamentos , Feminino , Ácido Fólico/química , Ácido Fólico/metabolismo , Grafite/química , Grafite/metabolismo , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanomedicina , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Polietilenoglicóis/química , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismoRESUMO
In this study, Gd2O2S:Ln3+ (Ln3+ = Yb3+, Er3+) upconversion nanotubes (UCNTs) were synthesised by using Gd(OH)3:Ln3+ (Ln3+ = Yb3+, Er3+) nanotubes as the template. The luminescent and biological properties of Gd2O2S:Ln3+ (Ln3+ = Yb3+, Er3+) UCNTs, along with photodynamic therapy (PDT) applications of the Gd2O2S:8%Yb3+,2%Er3+ UCNT-Ce6 (chlorin e6) nanocomposites, were systematically studied. The resultant UCNTs showed excellent biocompatibility with human retinal pigment cells (ARPE-19) even after a prolonged incubation time of 72â h, and could be used as luminescent probes. Microscopic imaging revealed that the UCNTs existed mainly in cytoplasm. PDT studies on the Gd2O2S:8%Yb3+,2%Er3+ UCNT-Ce6 nanocomposites indicate that the growth of the tumour (cell) could be inhibited dramatically when it was injected (incubated) with Gd2O2S:8%Yb3+,2%Er3+ UCNT-Ce6 nanocomposites under the irradiation of 980â nm laser.
