Assessing the Combinatorial Chemo‐Photothermal Therapy Mediated by Sulfobetaine Methacrylate‐Functionalized Nanoparticles in 2D and 3D In Vitro Cancer Models

Abstract

Combinatorial cancer therapies mediated by nanomaterials can potentially overcome the limitations of conventional treatments. These therapies are generally investigated using 2D in vitro cancer models, leading to an inaccurate screening. Recently, 3D in vitro spheroids have emerged in the preclinical testing stage of nanomedicines due to their ability to mimic key features of the in vivo solid tumors. Investigate the chemo-photothermal therapy mediated by Doxorubicin and IR780 loaded sulfobetaine methacrylate functionalized nanoparticles, for the first time, using monolayers of cancer cells and spheroids. In the 2D cancer models, the nanomaterials' mediated photothermal therapy, chemotherapy, and chemo-photothermal therapy reduced cancer cells' viability to about 58%, 29%, and 1%, respectively. Interestingly, when the nanomaterials' mediated photothermal therapy is tested on 3D spheroids, no cytotoxic effect is noticed. In contrast, the nanostructures' induced chemotherapy decreased spheroids' viability to 42%. On the other hand, nanomaterials' mediated chemo-photothermal therapy diminished spheroids' viability to 16%, being the most promising therapeutic modality. These results demonstrate the importance of using 3D spheroids during the in vitro screening of single/combinatorial therapies mediated by nanomaterials.

Injectable in situ forming hydrogels incorporating dual-nanoparticles for chemo-photothermal therapy of breast cancer cells

“…Then, the absorption of IR/BPN and DOX/TPN was analyzed (Figure S1B). As expected, the IR/BPN exhibited a peak at 791 nm (Figure S1B), which is characteristic of encapsulated IR780 (Alves et al, 2020;Mó et al, 2020). In turn, the DOX/TPN displayed the characteristic absorption peak of DOX at 485 nm (Moreira et al, 2014).…”

“…To determine the IR780 content in IR/BPN, these nanoparticles were freeze-dried (Canvas CoolSafe, Labo-Gene ApS, Lynge, Denmark) and then resuspended in 1 mL of water:methanol (1:1 (v/v)). Afterwards, a standard curve of IR780 (in 1:1 (v/v) water:methanol) and the absorbance of the IR/BPN sample at 780 nm were used to determine the content of IR780 (Mó et al, 2020). To determine the DOX content in DOX/TPN, these nanoparticles were also freeze-dried and resuspended in 1 mL of methanol.…”

3D imaging and quantification of PLL coated fluorescent ZnO NP distribution and ROS accumulation using laser scanning confocal microscopy

“…Breast cancer treatment includes various modalities like surgery, radiation therapy as well as drug therapy for the prevention of metastasis. Since these drugs have prominent cytotoxic effects on both cancerous and healthy cells, there is a significant effort in developing biocompatible nanoformulations that can be tailored to their intended applications as therapeutics 1–3 . Determination of bioavailability and toxicity of such nanoparticles (NPs) require the use of imaging approaches, ideally with three dimensional (3D) capabilities.…”

Nanomedicine: Sulfobetaine Methacrylate-Albumin-Coated Graphene Oxide Incorporating IR780 for Enhanced Breast Cancer Phototherapy

“…As importantly, SBMA-coated nanoparticles are not reported to suffer from the ABC phenomenon [50]. On the other hand, IR780 (a hydrophobic small molecule) was selected to be loaded on the graphitic lattice of GO due to its high NIR absorption [48,51]. Furthermore, the optical properties of IR780 are superior or equivalent to those displayed by other NIR responsive dyes such as indocyanine green and other prototypic heptamethine cyanines (e.g., IR775, IR783, IR797 and IR806) [52].…”