Patients with pancreatic cancer (PCa) have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic. Yet, it suffers from certain limitations during clinical exploitation, including insufficient photosensitizers (PSs) delivery, tumor-oxygenation dependency, and treatment escape of aggressive tumors. To overcome these obstacles, an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles (NPs) by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers. Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation. A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment. This review provides an overview of available data regarding the design, methodology, and oncological outcome of the innovative NPs-based PDT of PCa.
Hypoxic tumor microenvironment and
nonspecific accumulation of
photosensitizers are two key factors that limit the efficacy of photodynamic
therapy (PDT). Herein, a strategy of oxygen microbubbles (MBs) boosting
photosensitizer micelles is developed to enhance PDT efficacy and
inhibit tumor metastasis by self-assembling renal-clearable ultrasmall
poly(ethylene glycol)-modified protoporphyrin IX micelles (PPM) and
perfluoropentane (PFP)-doped oxygen microbubbles (OPMBs), followed
by ultrasound imaging-guided OPMB destruction to realize the tumor-targeted
delivery of PPM and oxygen in tumor. Doping PFP into oxygen MBs increases
the production of MBs and stability of oxygen MBs, allowing for persistent
circulation in blood. Following co-injection, destruction of OPMBs
with ultrasound leads to ∼2.2-fold increase of tumor-specific
PPM accumulation. Furthermore, the burst release of oxygen by MB destruction
improves tumor oxygenation from 22 to 50%, which not only raises the
production of singlet oxygen but also significantly reduces the expression
of hypoxia-inducible factor-1 alpha and related genes, thus preventing
angiogenesis and epithelial–mesenchymal transition. It is verified
that this strategy effectively eradicates orthotopic breast cancer
and inhibits lung metastasis. Furthermore, the survival rate of mice
bearing orthotopic pancreatic tumor is significantly extended by such
interventional PDT strategy. Therefore, the combination of ultrasmall
PPM and OPMBs represents a simple but effective strategy in overcoming
the limitations of PDT.
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