Protein Corona around Gold Nanorods as a Drug Carrier for Multimodal Cancer Therapy.
Eugenia Li Ling YeoJoshua U-Jin CheahBing Yi LimPatricia Soo Ping ThongKhee Chee SooJames Chen Yong KahPublished in: ACS biomaterials science & engineering (2017)
A single nanodevice based on gold nanorods (NRs) coloaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapeutic, Doxorubicin (Dox), on its endogenously formed human serum (HS) protein corona, i.e., NR-HS-Ce6-Dox was developed with the aim of performing multimodal cancer therapy: photodynamic (PDT), photothermal (PTT) and chemotherapy (CTX) simultaneously upon irradiation with a single 665 nm laser. Here, the excitation of NRs and Ce6 resulted in photothermal ablation (PTT), and production of reactive oxygen species (ROS) to kill Cal 27 oral squamous cell carcinoma (OSCC) cells by oxidative stress (PDT) respectively, while the laser-triggered release of Dox intercalated into the DNA of cancer cells to result in DNA damage and cell death (CTX). High laser-triggered Dox release efficiency of 71.5% and strong plasmonic enhancement of ROS production by Ce6 (4.8-fold increase compared to free Ce6) was observed. Uptake of both Ce6 and Dox by Cal 27 cells was greatly enhanced, with 3.3 and 52 times higher intracellular Dox and Ce6 fluorescence observed, respectively, 6 h after dosing with NR-HS-Ce6-Dox compared to free drugs. The simultaneous trimodal therapy achieved a near complete eradication of cancer cells (98.7% cell death) with an extremely low dose of 15 pM NR-HS-Ce6-Dox loaded with just 1.26 nM Ce6 and 12.5 nM Dox due to strong synergistic enhancement in cancer cell kill compared to individual therapies performed separately. No dark toxicities were observed. These drug concentrations were far lower than any previously reported in vitro, thus eliminating any potential systemic toxicity of these agents.
Keyphrases
- cancer therapy
- energy transfer
- photodynamic therapy
- cell death
- dna damage
- drug delivery
- oxidative stress
- cell cycle arrest
- reactive oxygen species
- low dose
- induced apoptosis
- quantum dots
- stem cells
- dna repair
- helicobacter pylori
- air pollution
- particulate matter
- pain management
- high speed
- risk assessment
- circulating tumor
- helicobacter pylori infection
- cell proliferation
- small molecule
- cell free
- mesenchymal stem cells
- protein protein
- radiation therapy
- klebsiella pneumoniae
- bone marrow
- signaling pathway
- endoplasmic reticulum stress
- catheter ablation
- amino acid
- reduced graphene oxide