Cell‐Derived Biogenetic Gold Nanoparticles for Sensitizing Radiotherapy and Boosting Immune Response against Cancer

Abstract

The biosynthesis of nanomedicine has gained enormous attention and exhibited promising prospects, while the underlying mechanism and advantage remain not fully understood. Here, a cell‐reactor based on tumor cells is developed to obtain biogenetic gold nanoparticles (Au@MC38) for sensitizing radiotherapy and boosting immune responses. It demonstrates that the intracellular biomineralization and exocytosis process of Au@MC38 can be regulated by the cellular metabolites level and other factors, such as glutathione and reactive oxygen species (ROS), autophagy, and UV irradiation. The elucidation of mechanisms may promote the understanding of interaction principles between nanoparticles and biosystems in the process of biosynthesis. Combined with radiotherapy, Au@MC38 strengthens the radiation‐induced DNA damage and ROS generation, thus aggravating cell apoptosis and necrosis. Benefiting from homologous targeting and transcytosis effect, Au@MC38 demonstrates good tumor distribution. Local radiation‐induced immunogenic cell death initiates an effective immune response. Especially, CD8a+ dendritic cells are significantly increased in mice that received combinatorial treatment. This radio‐sensitization strategy has demonstrated the effective inhibition on primary and metastatic tumors, and achieved satisfactory survival benefit in combinatorial with immune checkpoint blockade. Thus, this bio‐inspired synthetic strategy may impulse the development of biosynthesis and its therapeutic applications, contributing to a non‐invasive and efficient modality for nanomedicine exploitation.

Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy

“…Zhang et al . revealed that the intracellular synthesis of gold NPs was a complex process and was modulated by various factors, such as glutathione (GSH) and ROS . The precise mechanism of endocytosis and efflux of AIEgens from the DC reactor is not well understood thus far and deserves our further intensive investigation.…”

“…31 Zhang et al revealed that the intracellular synthesis of gold NPs was a complex process and was modulated by various factors, such as glutathione (GSH) and ROS. 28 The precise mechanism of endocytosis and efflux of AIEgens from the DC reactor is not well understood thus far and deserves our further intensive investigation. Dynamic light scattering (DLS) detection exhibited the sizes of isolated DEV-AIE and DEVs were 131.14 ± 5.25 nm and 92.73 ± 5.14 nm, and the corresponding PDI values were 0.249 and 0.275, respectively (Figure 2C and Table S2).…”

“…Most AIE luminogens (AIEgens) are hydrophobic, and they are encapsulated into amphiphilic polymers to formulate AIE nanoparticles (NPs) for in vivo PDT; , however, the resultant AIE-NPs encounter unsatisfactory loading content, limited encapsulation efficiency, and changed subcellular localization. , Our previous study also revealed that the AIE-NP formulation restricted the intramolecular motion and led to inefficient mitochondrial targeting, which could negatively affect the ICD induction . Although the precise mechanism for the cellular exocytosis of NPs is not well understood, mammalian cells that possess high biological homology and little immunogenicity have great potential as cell reactors for the synthesis of biocompatible NPs. − Of note, NPs can be exocytosed from cell reactors as EV-biomimetic NPs with both physiological characteristics of inherently secreted EVs and chemical properties of exogenous formulations. , For instance, Yang and co-workers biosynthesized exosome-sheathed porous silicon NPs based on tumor cells as a cell reactor for chemotherapy . Previous publications, including studies from our group, demonstrated that the integration of AIEgens with EVs does not affect the luminescence performance and PDT effects of AIEgens. ,, Furthermore, EVs are fascinating drug carriers due to their immune escape capacity endowed by tetraspanin CD47, good biocompatibility, and low toxicity; , therefore, the naturally exocytosed EV-biomimetic AIE-NPs from a cell reactor will not only solve the poor solubility of AIEgens but also enhance their circulation time, and the intramolecular motion and mitochondrial-targeting property could also avoid being altered, thereafter endowing AIEgens with increased ICD effects.…”

Engineered tumor cell-derived vaccines against cancer: The art of combating poison with poison

“…In addition to delivering small molecule drugs, TEXs can be manipulated to load gold nanoparticles. For example, tumor cells can be cultured in a medium containing HAuCl 4 solution, and the cells can be used to synthesize gold nanoparticles and release them directly as TEX-encapsulated gold nanoparticles (Au@MC38) [ 151 ] ( Fig. 3 C and D).…”

Candesartan induces tumor vascular normalization to improve the efficacy of radiotherapy in the therapeutic window

“…A Clinical study has confirmed that the oxygen content of tumor cells has a great effect on the killing effect of radiation (4). This is because the high-energy ionizing radiation generated during RT can produce reactive oxygen species (ROS) in the aerobic microenvironment, which in turn damage the normal structure of tumor deoxyribonucleic acid (DNA) and cause tumor cell death (4,5). Thus, the therapeutic effect of RT is positively correlated with the partial pressure of oxygen inside the solid tumor.…”