Abstract
Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. However, the efficacy of PDT in treating a deep-seated tumor is limited due to three main reasons: Limited light penetration depth, low oxygen concentration in the hypoxic core, and poor PS accumulation inside a tumor. Thus, PDT treatments are only approved for superficial and thin tumors. With the advancement of nanotechnology, PDT to treat deep-seated or thick tumors is becoming a reachable goal. In this review, we provide an update on the strategies for improving PDT with nanomedicine using different sophisticated-design nanoparticles, including two-photon excitation, X-ray activation, targeting tumor cells with surface modification, alteration of tumor cell metabolism pathways, release of therapeutic gases, improvement of tumor hypoxia, and stimulation of host immunity. We focus on the difficult-to-treat pancreatic cancer as a model to demonstrate the influence of advanced nanomedicine in PDT. A bright future of PDT application in the treatment of deep-seated tumors is expected.
Highlights
The earliest light therapy for various skin diseases can be traced back to ancient Greece, Egypt, and India [1,2]
The third NIR biological window signifying the range of wavelengths from 1550 to 1870 nm has been developed and can achieve a superb light penetration depth into the human body [20]. Another feasible technique is two-photon excitation (TPE) which allows the use of a lower energy irradiation to activate PSs with two-photon absorption (TPA), resulting in a significant improvement in the light penetration depth throughout the body and reducing the additional photodamage to healthy tissue (Figure 3) [21]
The porous metal–organic framework (MOF) nanomaterial constructed by metal complexes and organic ligands under an orderly arrangement has emerged as a candidate in the field of nanomedicine, showing various applications such as gas loading, photo-catalysis, and drug delivery, as well as exhibiting good biocompatibility and biodegradability [62]
Summary
The earliest light therapy for various skin diseases can be traced back to ancient Greece, Egypt, and India [1,2]. Von Tappeiner and his partner, Dr Jesionek, treated skin cancers, lupus of the skin, and condyloma with eosin dye with PDT, as reported in their book. Photofrin is still the most commonly used PS globally It has many disadvantages, including a long half-life lasting for weeks to months that leads to skin photosensitivity, and a small absorbance peak at 630 nm making it difficult to penetrate bulky tumors [3]. The advantages of PDT include high selectivity to cancer cells and a high safety profile without long-term side effects It can be performed as an outpatient procedure, can be repeated if necessary, is less expensive than other treatments, and can be used as a curative or an adjuvant therapy. We use pancreatic cancer, a deep-seated tumor that is very challenging to treat, as a model to demonstrate how nanomedicine can be used as a potential tool to improve PDT
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