Near-Infrared Light-Initiated Upconversion Nanoplatform with Tumor Microenvironment Responsiveness for Improved Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is inflowing the mainstream of the cancer treatments, yet the shallow light penetration, thermal damage to normal cells, poor tumor targeting, and skin phototoxicity compromised the PDT efficacy. This paper designed and prepared an upconversion nanoplatform that could effectively convert 808 nm NIR light to red and green light emission, both of which could excite photosensitizers and exert the PDT curative effects. A thin layer of mesoporous silica covering core− shell nanostructure NaGdF 4 :Yb,Er@NaGdF 4 :Yb,Nd upconversion nanoparticles was prepared as the carrier to load the photosensitizer pyropheophorbide-a (PPa), which could be excited by green and red light simultaneously and produce high singlet oxygen ( 1 O 2 ) quantum yield (79.1%). Meanwhile, the chemotherapy drug doxorubicin (DOX) was absorbed in the pores of the SiO 2 layer to improve the therapeutic effect, and the folic acid-coupled chitosan (Cs-FA) was modified on the surface of the SiO 2 layer to obtain the targeting and biocompatible UCNP@SiO 2 /PPa&DOX@Cs-FA nanoplatform. The physically adsorbed DOX in the pore channel could be released slowly under faintly acidic or GSH stimuli (84% release of DOX after 16 h), suggesting that the nanoplatform was responsive to the tumor microenvironment. In vitro experiments showed that the combined treatment of PDT and DOX was superior to that of PDT alone or DOX chemotherapy alone, implying a synergistic therapeutic effect. The morphological changes and dye staining research of HeLa cells were consistent with the MTT assay. Therefore, this research provided a strategy for the development of an efficient and safe multifunctional cancer treatment nanoplatform integrating low-intensity light excitation, slow release, targeting, photodynamic therapy, and chemotherapy.

Facile Multistep Synthesis of ZnO-Coated β-NaYF4:Yb/Tm Upconversion Nanoparticles as an Antimicrobial Photodynamic Therapy for Persistent Staphylococcus aureus Small Colony Variants

“…Lanthanide-doped upconversion nanoparticles (UCNPs) have been recently used as a novel class of PS nanomaterials for PDT against cancer cells. − Core/shell nanoparticles consisting of an UCNP as the core and a semiconductor coating (e.g., ZnO or TiO 2 ) can be used as a PS. These materials generate ROS upon activation by near-infrared (NIR) light, which is absorbed by the UCNP core and which in turn emits visible and UV light that is used to excite the semiconductor and produce the reactive oxygen species (Scheme ).…”

Inorganic–inorganic nanohybrids for drug delivery, imaging and photo-therapy: recent developments and future scope

“…Even though the in vitro results are promising, the lack of pre-clinical studies using an animal model makes it difficult to predict their clinical relevance. 165 5.3 Inorganic-inorganic nanohybrids for combined PTT/ PDT/imaging applications BSA-stabilized Gd 2 O 3 -Au nano crystals (NCs) were made as contrast agents in MRI and CT imaging (Fig. 10).…”

“…Even though the in vitro results are promising, the lack of pre-clinical studies using an animal model makes it difficult to predict their clinical relevance. 165 …”

Combined cancer therapeutics—Tackling the complexity of the tumor microenvironment

“…The increased abundance of proteins at the TME inspired the creation of NPs for TME targeting and/or for stimuli‐responsive therapeutics (Y. Zhou, Chen, et al, 2020). Examples of these strategies are the AS1411‐GO/B3, Glc@PDA‐BTZ and Glc‐DEG@ PDA‐BTZ and UCNP@SiO2/PPa&DOX@Cs‐FA nanoparticles designed to target Nucleolin, Glut‐1 proteins and folic acid (FA) receptors, respectively, revealed to be efficient to target tumor cells while increasing the effect of cytotoxic payload and displaying effective PTT capabilities (Du et al, 2020; Y. Li, Hong, et al, 2020; X. Wu, Zhang, et al, 2020). In the three cases, the acidic environment of the TME increased the release of the cytotoxic payload.…”