As an emerging antitumor strategy, photodynamic therapy (PDT) has attracted intensive attention for the treatment of various malignant tumors owing to its noninvasive nature and high spatial selectivity in recent years. However, the therapeutic effect is unsatisfactory on some occasions due to the presence of some unfavorable factors including nonspecific accumulation of PS towards malignant tissues, the lack of endogenous oxygen in tumors, as well as the limited light penetration depth, further hampering practical application. To circumvent these limitations and improve real utilization efficiency, various enhanced strategies have been developed and explored during the past years. In this review, we give an overview of the state-of-the-art advances progress on versatile nanoplatforms for enhanced PDT considering the enhancement from targeting or responsive, chemical and physical effect. Specifically, these effects mainly include organelle-targeting function, tumor microenvironment responsive release photosensitizers (PS), self-sufficient O2 (affinity oxygen and generating oxygen), photocatalytic water splitting, X-rays light stimulate, surface plasmon resonance enhancement, and the improvement by resonance energy transfer. When utilizing these strategies to improve the therapeutic effect, the advantages and limitations are addressed. Finally, the challenges and prospective will be discussed and demonstrated for the future development of advanced PDT with enhanced efficacy.

Versatile Nanoplatforms with enhanced Photodynamic Therapy: Designs and Applications.

Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed.

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Therapeutic applications of nucleic acid aptamers in microbial infections.

Therapeutic oxygen delivery by perfluorocarbon-based colloids

Light-powered catalysis has found broad utility as a chemical transformation strategy, with widespread impact on energy, environment, drug discovery and human health. A noteworthy application impacting human health is light-induced sensitization of cofactors for photodynamic therapy in cancer treatment. The clinical adoption of this photosensitization approach has inspired the search for other photochemical methods, such as photoredox catalysis, to influence biological discovery. Over the past decade, light-mediated catalysis has enabled the discovery of valuable synthetic transformations, propelling it to become a highly utilized chemical synthesis strategy. The reaction components required to achieve a photoredox reaction are identical to photosensitization (catalyst, light source and substrate), making it ideally suited for probing biological environments. In this Review, we discuss the therapeutic application of photosensitization and advancements made in developing next-generation catalysts. We then highlight emerging uses of photoredox catalytic methods for protein bioconjugation and probing complex cellular environments in living cells. Photocatalysis is widely used in numerous fields, including chemistry and biology. This Review highlights the impact of photosensitization and photoredox photocatalysis within therapeutic development, bioconjugation and for probing complex cellular environments.

Interrogating biological systems using visible-light-powered catalysis

Bio-imaging and therapeutic nanoparticles-initially two different research areas tend more and more to merge. The outcome? Highly sophisticated imaging techniques offering new insights in nature or reducing side-effects of clinical therapies-a perfect symbiosis. This symbiosis is reflected in large improvements of medical diagnostics and therapy and even led to the formation of a completely new approach named “theranostics”, the fusion of the two areas therapeutics and diagnostics. Imaging of biological tissue dates back to 1900’s. The X-ray illumination of the hand of Wilhelm Roentgen's wife in 1895 was the first medical image exposing the unseen world inside the living body. In parallel, the synthesis, characterization and use of nanoparticles advanced leading inescapably to the idea to combine both fields. If nanoparticles can be used to specifically deliver drugs to target tissues why shouldn ́t they transport e.g. contrast agents necessary for clinical imaging?

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Nano-bio-imaging and therapeutic nanoparticles

Photodynamic therapy (PDT) and photothermal therapy (PTT) belong to the category of phototherapy and are based on the photophysical generation of either noxious reactive oxygen species, thereby inducing oxidative stress, or rather cell-hostile environmental conditions (local hyperthermia) with the general aim to destroy abnormal tissues. A great advantage of both strategies is the fact that they are minimally invasive by low toxicity for the surrounding healthy tissue. In both cases, photosensitizers and light are inevitable. Furthermore, in PDT oxygen is a mandatory component for generating reactive oxygen species such as singlet oxygen. Perfluorocarbons (PFCs) can donate molecular oxygen tension in the target tissue of interest (tumor tissue) thereby improving PDT outcome in such a hypoxic region. Because applied PFCs can at the same monitored via both, ultrasonic and magnetic resonance imaging techniques, they increase the selectivity of PDT and PTT to target tissue while sparing healthy cells in the surroundings. This selectivity is especially important in tissues such as eye, brain or gastro-intestinal tract. During the last few years a lot of interesting approaches (clinical and preclinical) were developed to improve PDT and PTT with the aid of PFCs. This review informs the astute reader about actual approaches on the use of PFCs in PDT and PTT, respectively. The literature indicates that the use of PFCs can increase the efficiency of PDT and PTT thereby contributing to a more effective therapy of tumors and other diseases.

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Scheer A

Papers

Perfluorocarbons in photodynamic and photothermal therapy