Photodynamic and photothermal therapy using PLGA nanoparticles

The use of nanomaterials in advancing photodynamic therapy (PDT) for deep-seated tumors and synergy with radiotherapy

“…These issues can be particularly important with newer organic or inorganic PS constructs in order to trade biocompatibility and efficacy (Shim et al, 2022). Although some advantages can be achieved through conjugation of standard molecular PSs with antibodies, folate moieties or other small molecules, the majority of third-generation PDT approaches use nanoparticle systems (Dinakaran et al, 2023).…”

“…LNPs here refer to a family of lipid-based nanoparticles such as micellar structures (single layer phospholipid with hydrophobic interior), liposomes (bi-layer phospholipids with physiologic interior environment), solid LNPs (admixture of lipids along with payload) and similar carriers. These are an attractive carrier system for PS because of the extensive research that has made them stable, biocompatible, have favorable distribution properties and drug release kinetics, provide passive targeting through the enhanced permeability and retention (EPR) effect or allow active targeting via aptamers, allow simultaneous co-delivery of other cancer drugs, and make even natively toxic drugs feasible to use in humans (Avci et al, 2014;Dinakaran et al, 2023). Beyond this obvious advantage, further development of LNP-based PDT agents has resulted in some new strategies in leveraging nanoparticles for PDT.…”

“…Beyond LNPs, the next most common nanocarrier platform for PSs is polymeric nanoparticles such as poly-lactic-co-glycolic acid (PLGA). PLGA also has a track record of preclinical and clinical use to carry chemotherapeutic agents, albeit less developed than LNPs (Dinakaran et al, 2023). For the PLGA may have some advantages over LNP for photosensitizer delivery.…”

“…One exemplary technique would be the use high-energy X-rays as delivered, for example, in clinical radiotherapy using a LINAC but at a low, well-tolerated radiation dose (typically, <10 Gy). The preclinical studies of this technique have frequently exploited different nanoparticle formulations, either as X-ray activatable materials and/or as delivery vehicles for molecular photosensitizers (Dinakaran et al, 2023). Several specific molecular radioPDT agents are also being developed (Larue et al, 2018), as well as an emerging approach is the use of nanoclusters, whose small number (~10-30) of gold or silver atoms confers molecule-like quantum energy levels that result in singlet oxygen generation under X-ray exposure (van de Looij et al, 2022).…”

“…To date, only one study has systematically evaluated this: the cytotoxic effect was indeed reduced under highly hypoxic conditions but was preserved, at least in vitro, for pO 2 >1% by optimizing the concentration of the PEG-PLGA encapsulated LaF 3 : Ce 3+ nanoscintillator and PpIX photosensitizer nanoparticles and the radiation dose (Dinakaran et al, 2019); e.g., the cytotoxicity benefit of radioPDT over radiation alone was as high as 50% even under hypoxic conditions. Other groups have demonstrated the use of high quantum efficiency metallo-organic photosensitizer complexes (Azad et al, 2023) that are efficient in normoxia and hypoxia as well as oxygen-independent inorganic photosensitizers such as psolarens (Pathak, 1984;Zhang et al, 2015a), although delivery of these to poorly vascularized tumors may still be limiting. Use of the Type I reaction pathway, which relies on electron transfer to generate oxy and hydroxy radicals, is a further potential strategy to mitigate the effect of tumor hypoxic (Zhang et al, 2015b) and has demonstrated efficacy both in vitro and in vivo at physiologic tumor environments, including hypoxia (Dinakaran et al, 2019).…”