A Transformable Nanomedicine for Smart Cancer Therapy by Identifying the Environmental Characteristics

Abstract

Photodynamic therapy (PDT) has attracted much attention in recent years due to its high selectivity; however, limited by the heterogeneity of a tumor oxygen environment, the hypoxic region of a tumor will be significantly resistant to PDT. Herein, we report an oxygen level-responsive transformable therapeutic nanomedicine consisting of a hypoxiaresponsive molecule (Cy-NO 2 ), a radical generator (ADVN), and a pH-responsive polymer. In the normoxic region, Cy-NO 2 in the nanomedicine plays the role of photosensitizer under 808 nm laser irradiation to realize effective PDT, while in hypoxic intracellular conditions, the Cy-NO 2 will be converted into a photothermal agent, which can induce the decomposition of ADVN through photothermal effect to generate toxic free radicals for thermodynamic therapy. Therefore, by identifying the environmental characteristics and transforming treatment approaches, this nanomedicine can achieve good therapeutic effects under both normoxic and hypoxic conditions. This work offers a promising strategy for overcoming oxygen heterogeneity to achieve smart cancer therapy.

Constructing Singlet Oxygen “Slow Release” Platform to Optimize the Performance of Commercial Photosensitizers

“…Photodynamic therapy (PDT), utilizing reactive oxygen species (ROS) including singlet oxygen ( 1 O 2 ), [ 1–4 ] superoxide anion free radical (O 2 −∙ ), [ 5–10 ] hydroxyl radical (OH∙), [ 11–14 ] and so on generated by photosensitizers (PSs) to oxidize cancer cells, holds tremendous promise for cancer treatment owing to its high selectivity, minimal invasiveness, and low systemic cytotoxicity. [ 15–18 ] Currently, most commercial PSs applied in clinics mainly rely on the high 1 O 2 generation to achieve tumor ablation, for instance, Ce6, ICG, MB, etc . [ 19–21 ] However, 1 O 2 exhibits an extremely short lifespan (10–320 ns) and a small diffusion range (10–55 nm) within the cell.…”

Reactive Oxygen Species-Activated Self-Accelerated Drug Release Nanoparticles for Enhanced Cancer Combination Therapy

“…The use of various stimuli-responsive linkers and the mechanisms of prodrug activation have been extensively studied in the last few decades. − Notably, due to the higher levels of reactive oxygen species (ROS) in cancer cells compared to normal cells, prodrugs activated by ROS have higher tumor selectivity. − Currently, many different types of ROS-activated prodrugs and polyprodrugs based on arylboronates-, thiazolidinones-, selenium-, or sulfur-containing linkers, have been developed. − However, insufficient endogenous ROS often limits effective prodrug activation . ROS-based treatment approaches including photodynamic therapy, sonodynamic therapy, and chemodynamic therapy (CDT) have been developed. − Although ROS amplification strategies can be exploited to improve the intracellular ROS level, − they may also reduce the selectivity of prodrug activation. Therefore, the development of an endogenous ROS-activated polyprodrug-based nanoparticle with high selectivity and continuous effective drug release is of great significance.…”

Hypoxia Exacerbation-Triggered Doxorubicin Prodrug Activation for Sequential Photodynamic/Chemotherapy

“…Recently, several approaches have been reported to aggravate hypoxia, such as increasing oxygen consumption and reducing oxygen supply. , Among them, photodynamic therapy (PDT), which can produce a high level of singlet oxygen ( 1 O 2 ) by consuming oxygen, is an effective approach to realize aggravated hypoxia and activation of hypoxia-responsive prodrugs. , More importantly, PDT can be applied as a local therapy by controlling the position of light application. − Therefore, the combination of PDT with hypoxia-activated prodrugs does not impair the tumor selectivity of the prodrugs, thereby reducing damage to normal tissues.…”