Cancer Cell Membrane Camouflaged Nanoparticles to Realize Starvation Therapy Together with Checkpoint Blockades for Enhancing Cancer Therapy

Abstract

Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN’s biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.

Controlled synthesis of a core-shell nanohybrid for effective multimodal image-guided combined photothermal/photodynamic therapy of tumors

“…Through a straightforward strategy, a series of PB@PCN nanohybrids with different shell thicknesses were prepared. The PB@PCN nanohybrid with the optimal shell thickness was further camouflaged by mouse colon cancer cell (CT26) membranes (PB@PCN@MEM) to endow the nanohybrid with good immune evasion and an active targeting ability [33][34][35] . As illustrated in Scheme 1, the PCN shell, with the advantages of facile diffusion of singlet oxygen ( 1 O 2 ), avoidable self-quenching and high photosensitizer (PS) loading, could efficiently convert O 2 into highly toxic 1 O 2 to kill tumor cells by PDT and attack HSPs to promote the PTT effect 36 .…”

Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

“…This will facilitate proper orientation of the membrane around the NP owing to electrostatic repulsion between the NP surface and negative extracellular membrane components [27]. To date, the types of synthetic NPs that have been wrapped with cell-derived membranes for cancer therapies include nanocrystals [54], nanocages [42], mineral-based or mesoporous silica [35,49,[55][56][57][58], polymeric cores [30,40,45,[59][60][61][62][63][64], organic and inorganic metal frameworks [44,51,[65][66][67], protein cores [68,69], and gold-based or magnetic nanoparticles [70][71][72] (Figure 4, Table 1). Poly(lactic-co-glycolic) acid (PLGA) is one of the most widely used NP cores due to its biodegradability, FDA approval, and ability to encapsulate many products [17][18][19].…”

“…This system has potential to solve hypoxia issues in tumors and promote starvation. Starvation therapy mediated by membrane-wrapped NPs has also been explored without PDT [55]. In this study, GOx-loaded membrane-wrapped mesoporous silica NPs were combined with PD-1 antibody treatment and shown to be more effective at stimulating an anti-cancer immune response than the single therapies, resulting in better cancer ablation.…”

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

“…A new approach of targeting different TME components using nanoparticles has been recently proposed [130]. In melanoma mouse models, nanoparticles were shown to potentiate the efficiency of PD-1 blockade [131][132][133], to reduce the tumor volume and to prolong mouse survival [134].…”