Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.
Photodynamic
therapy (PDT) shows a promising synergy with chemotherapy
in the therapeutic outcome of malignant cancers. The minimal invasiveness
and nonsystemic toxicity are appealing advantages of PDT, but combination
with chemotherapy brings in the nonselective toxicity. We designed
a polymeric nanoparticle system that contains both a chemotherapeutic
agent and a photosensitizer to seek improvement for chemo-photodynamic
therapy. First, to address the challenge of efficient co-delivery,
polymer-conjugated doxorubicin (PEG-PBC-TKDOX) was synthesized to
load photosensitizer chlorin e6 (Ce6). Ce6 is retained with DOX by
a π–π stacking interaction, with high loading (41.9
wt %) and the optimal nanoparticle size (50 nm). Second, light given
in PDT treatment not only excites Ce6 to produce cytotoxic reactive
oxygen species (ROS) but also spatiotemporally activates a cascade
reaction to release the loaded drugs. Finally, we report a self-destructive
polymeric carrier (PEG-PBC-TKDOX) that depolymerizes its backbone
to facilitate drug release upon ROS stimulus. This is achieved by
grafting the ROS-sensitive pendant thioketal to aliphatic polycarbonate.
When DOX is covalently modified to this polymer via thioketal, target specificity is controlled by light, and off-target
delivery toxicity is mostly avoided. An oral squamous cell carcinoma
that is clinically relevant to PDT was used as the cancer model. We
put forward a polymeric system with improved efficiency for chemo-photodynamic
therapy and reduced off-target toxicity.
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