Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy

Abstract

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

Fullerene/photosensitizer nanovesicles as highly efficient and clearable phototheranostics with enhanced tumor accumulation for cancer therapy

“…72 Free radical species detection was subsequently carried out to identify which kind of ROS was produced by FCNVs upon laser irradiation with different ROS scavengers. 20 In contrast, the added free radical inhibitors (mannitol and SOD) did not protect cells from…”

Polydopamine-based Materials as Carriers for Drug Delivery

“…Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, PDA-Ce6 had low dark toxicity, while excellent phototoxicity under the combination laser irradiation [22].…”

Smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release, photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma

“…Coincidentally, photodynamic therapy (PDT) was an oxygen-dependent therapeutic modality; it could aggravate the hypoxia within local tumor regions via continuous oxygen (O 2 ) consumption by photosensitizer (PS), and generate reactive oxygen species (ROS) induced tumor cell apoptosis and necrosis simultaneously under the adaptive laser irradiation 10. Chlorin e6 (Ce6) has been widely applied for PDT, due to its relatively rapid elimination from the body, high singlet oxygen generation efficiency, and could activated by NIR light; furthermore, the existence of carboxy makes it suitable for further conjugation or modification 11. Nevertheless, the potential photo-toxicity of Ce6 which generates ROS could nonspecifically damage the vascular system and normal tissues once exposed to the sun light, can make serious side effects in patients including burn, swelling and pain 12.…”