Controllable Assembly of Upconversion Nanoparticles Enhanced Tumor Cell Penetration and Killing Efficiency

Abstract

Photodynamic therapy (PDT) involves the activation of photosensitizers (PS) with a UV-visible (UV-vis) light source resulting in free radical production for tumor eradication. However, UV-vis light penetrates poorly and undergoes scattering in biological tissues. Hence, the use of upconversion nanoparticles (UCNPs) and near-infrared (NIR) light has been gaining traction in recent years. NIR light can relieve the scattering effect and has better tissue penetration, while UCNPs can convert NIR light to UV-vis light for PS activation. In this study, we report the efficacy of UCNPs clusters, generated by controlled assembly method and loaded with Chlorin e6 (Ce6), in inducing toxicity in vitro. An amphiphilic polymer, poly(styrene-co-maleic anhydride)(PSMA), was used to program UCNPs assembly by adjusting the polymer-to-UCNPs weight ratio (4.4 to 26.25). During particle assembly, Ce6 was loaded in the gap zones formed between connecting UCNPs. Adjusting the weight ratio led to the assembly of UCNPs cluster sizes from ~24nm to 140nm. UV absorption spectra revealed a concomitant increase in Ce6 loading with increasing cluster size. Cluster sizes of 24nm (single), 60nm (small), and 120nm (big) were used in subsequent studies. When excited with 980nm laser, energy transfer from UCNP to encapsulated Ce6 results in singlet oxygen formation. Big clusters showed the most superior singlet oxygen production, followed by small and single clusters. However, small clusters delivered the most Ce6 in 3D spheroids (MFI:1519) compared to free Ce6 (542.9), big (1170), and single clusters (837.1). Small clusters emerged top in killing 3D spheroids when excited with a visible light source. Although big clusters were superior in forming singlet oxygen, small clusters were the best nanocarrier for penetrating and killing 3D spheroids. The results indicated that the cluster sizes have different strengths, which can be exploited to facilitate their use as nanocarriers for cancer PDT.