Regulating Near-Infrared Photodynamic Properties of Semiconducting Polymer Nanotheranostics for Optimized Cancer Therapy

Abstract

Development of optical nanotheranostics for the capability of photodynamic therapy (PDT) provides opportunities for advanced cancer therapy. However, most nanotheranostic systems fail to regulate their generation levels of reactive oxygen species (ROS) according to the disease microenvironment, which can potentially limit their therapeutic selectivity and increase the risk of damage to normal tissues. We herein report the development of hybrid semiconducting polymer nanoparticles (SPNs) with self-regulated near-infrared (NIR) photodynamic properties for optimized cancer therapy. The SPNs comprise a binary component nanostructure: a NIR-absorbing semiconducting polymer acts as the NIR fluorescent PDT agent, while nanoceria serves as the smart intraparticle regular to decrease and increase ROS generation at physiologically neutral and pathologically acidic environments, respectively. As compared with nondoped SPNs, the NIR fluorescence imaging ability of nanoceria-doped SPNs is similar due to the optically inactive nature of nanoceria; however, the self-regulated photodynamic properties of nanoceria-doped SPN not only result in dramatically reduced nonspecific damage to normal tissue under NIR laser irradiation but also lead to significantly enhanced photodynamic efficacy for cancer therapy in a murine mouse model. This study thus provides a simple yet effective hybrid approach to modulate the phototherapeutic performance of organic photosensitizers.

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

“…SPNs constitute not only a new generation of organic nanoparticles for sensing and imaging139, 140, 141, 142, 143 but also a noninvasive remote control method with a near‐infrared absorbing property to regulate in vivo gene expression and cellular signals 135, 142, 144. What is particularly exciting is their potential in optimized cancer therapy 145, 146. The prospective integration of EVs and SPNs will have integrated superiority, such as targeting and controllability, just like the integration of liposomes and EVs, making them star performers in personalized and precision medicine.…”

Therapeutic Considerations and Conjugated Polymer‐Based Photosensitizers for Photodynamic Therapy

“…In 2017, Pu and co‐workers report a hybrid intraparticle doping approach to regulate the NIR photodynamic properties of conjugated polymer nanoparticles for optimized cancer therapy . The nanotheranostics were composed of NIR‐absorbing conjugated polymer and cerium oxide nanoparticle (nanoceria) to serve as the fluorescent PDT agent and the ROS regulator, respectively.…”

“…f) Mean tumor temperature as a function of laser irradiation time. g) Tumor growth curves of different groups of mice with and without laser irradiation . Copyright 2017, American Chemical Society.…”

A Semiconducting Polymer Nano‐prodrug for Hypoxia‐Activated Photodynamic Cancer Therapy

“…[10] To overcome this issue,t wo strategies have been developed. [23] In this work, we synthesize as emiconducting polymer nano-prodrug (SPNpd) with aw ell-defined structure for hypoxia-activated synergistic cancer therapy.T his nanoprodrug is assembled from an amphiphilic semiconducting brush polymer grafted with chemodrug side chains through hypoxia-cleavable linkers.Ithas the following three key units ( Figure 1a): Al ight-responsive photodynamic SPN core, ah ypoxia-cleavable linker,a nd the chemotherapeutic drug, ab romoisophosphoramide mustard intermediate (IPM-Br). [11] Theo ther is to combine PDT with chemotherapy,w hich uses the hypoxia-responsive carrier to encapsulate both photosensitizers and chemodrugs into the nanoparticles.…”

“…[21] Moreover,s tructural modification of precursor polymers has led to SPNbased phototherapeutic agents able to convert photoenergy to heat or ROSf or PTT or PDT. [23] In this work, we synthesize as emiconducting polymer nano-prodrug (SPNpd) with aw ell-defined structure for hypoxia-activated synergistic cancer therapy.T his nanoprodrug is assembled from an amphiphilic semiconducting brush polymer grafted with chemodrug side chains through hypoxia-cleavable linkers.Ithas the following three key units ( Figure 1a): Al ight-responsive photodynamic SPN core, ah ypoxia-cleavable linker,a nd the chemotherapeutic drug, ab romoisophosphoramide mustard intermediate (IPM-Br). [23] In this work, we synthesize as emiconducting polymer nano-prodrug (SPNpd) with aw ell-defined structure for hypoxia-activated synergistic cancer therapy.T his nanoprodrug is assembled from an amphiphilic semiconducting brush polymer grafted with chemodrug side chains through hypoxia-cleavable linkers.Ithas the following three key units ( Figure 1a): Al ight-responsive photodynamic SPN core, ah ypoxia-cleavable linker,a nd the chemotherapeutic drug, ab romoisophosphoramide mustard intermediate (IPM-Br).…”